Development and impact of computerised decision support systems for clinical management of depression: A systematic review.

PubMed

Triñanes, Yolanda; Atienza, Gerardo; Louro-González, Arturo; de-las-Heras-Liñero, Elena; Alvarez-Ariza, María; Palao, Diego J

2015-01-01

One of the proposals for improving clinical practice is to introduce computerised decision support systems (CDSS) and integrate these with electronic medical records. Accordingly, this study sought to systematically review evidence on the effectiveness of CDSS in the management of depression. A search was performed in Medline, EMBASE and PsycInfo, in order to do this. The quality of quantitative studies was assessed using the SIGN method, and qualitative studies using the CASPe checklist. Seven studies were identified (3 randomised clinical trials, 3 non-randomised trials, and one qualitative study). The CDSS assessed incorporated content drawn from guidelines and other evidence-based products. In general, the CDSS had a positive impact on different aspects, such as the screening and diagnosis, treatment, improvement in depressive symptoms and quality of life, and referral of patients. The use of CDSS could thus serve to optimise care of depression in various scenarios by providing recommendations based on the best evidence available and facilitating decision-making in clinical practice. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

'PhysioDirect' telephone assessment and advice services for physiotherapy: protocol for a pragmatic randomised controlled trial

PubMed Central

Salisbury, Chris; Foster, Nadine E; Bishop, Annette; Calnan, Michael; Coast, Jo; Hall, Jeanette; Hay, Elaine; Hollinghurst, Sandra; Hopper, Cherida; Grove, Sean; Kaur, Surinder; Montgomery, Alan

2009-01-01

Background Providing timely access to physiotherapy has long been a problem for the National Health Service in the United Kingdom. In an attempt to improve access some physiotherapy services have introduced a new treatment pathway known as PhysioDirect. Physiotherapists offer initial assessment and advice by telephone, supported by computerised algorithms, and patients are sent written self-management and exercise advice by post. They are invited for face-to-face treatment only when necessary. Although several such services have been developed, there is no robust evidence regarding clinical and cost-effectiveness, nor the acceptability of PhysioDirect. Methods/Design This protocol describes a multi-centre pragmatic individually randomised trial, with nested qualitative research. The aim is to determine the effectiveness, cost-effectiveness, and acceptability of PhysioDirect compared with usual models of physiotherapy based on patients going onto a waiting list and receiving face-to-face care. PhysioDirect services will be established in four areas in England. Adult patients in these areas with musculoskeletal problems who refer themselves or are referred by a primary care practitioner for physiotherapy will be invited to participate in the trial. About 1875 consenting patients will be randomised in a 2:1 ratio to PhysioDirect or usual care. Data about outcome measures will be collected at baseline and 6 weeks and 6 months after randomisation. The primary outcome is clinical improvement at 6 months; secondary outcomes include cost, waiting times, time lost from work and usual activities, patient satisfaction and preference. The impact of PhysioDirect on patients in different age-groups and with different conditions will also be examined. Incremental cost-effectiveness will be assessed in terms of quality adjusted life years in relation to cost. Qualitative methods will be used to explore factors associated with the success or failure of the service, the acceptability of PhysioDirect to patients and staff, and ways in which the service could be improved. Discussion It is still relatively unusual to evaluate new forms of service delivery using randomised controlled trials. By combining rigorous trial methods with economic analysis of cost-effectiveness and qualitative research this study will provide robust evidence to inform decisions about the widespread introduction of PhysioDirect services. Trial registration Current Controlled Trials ISRCTN55666618 PMID:19650913

The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) - a multicentre parallel-group randomised trial to compare early computerised tomography coronary angiography versus standard care in patients presenting with suspected or confirmed acute coronary syndrome: study protocol for a randomised controlled trial.

PubMed

Gray, Alasdair J; Roobottom, Carl; Smith, Jason E; Goodacre, Steve; Oatey, Katherine; O'Brien, Rachel; Storey, Robert F; Na, Lumine; Lewis, Steff C; Thokala, Praveen; Newby, David E

2016-12-07

Emergency department attendances with chest pain requiring assessment for acute coronary syndrome (ACS) are a major global health issue. Standard assessment includes history, examination, electrocardiogram (ECG) and serial troponin testing. Computerised tomography coronary angiography (CTCA) enables additional anatomical assessment of patients for coronary artery disease (CAD) but has only been studied in very low-risk patients. This trial aims to investigate the effect of early CTCA upon interventions, event rates and health care costs in patients with suspected/confirmed ACS who are at intermediate risk. Participants will be recruited in about 35 tertiary and district general hospitals in the UK. Patients ≥18 years old with symptoms with suspected/confirmed ACS with at least one of the following will be included: (1) ECG abnormalities, e.g. ST-segment depression >0.5 mm; (2) history of ischaemic heart disease; (3) troponin elevation above the 99 th centile of the normal reference range or increase in high-sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' of myocardial infarction (MI). The early use of ≥64-slice CTCA as part of routine assessment will be compared to standard care. The primary endpoint will be 1-year all-cause death or recurrent type 1 or type 4b MI at 1 year, measured as the time to such event. A number of secondary clinical, process and safety endpoints will be collected and analysed. Cost effectiveness will be estimated in terms of the lifetime incremental cost per quality-adjusted life year gained. We plan to recruit 2424 (2500 with ~3% drop-out) evaluable patients (1212 per arm) to have 90% power to detect a 20% versus 15% difference in 1-year death or recurrent type 1 MI or type 4b MI, two-sided p < 0.05. Analysis will be on an intention-to-treat basis. The relationship between intervention and the primary outcome will be analysed using Cox proportional hazard regression adjusted for study site (used to stratify the randomisation), age, baseline Global Registry of Acute Coronary Events score, previous CAD and baseline troponin level. The results will be expressed as a hazard ratio with the corresponding 95% confidence intervals and p value. The Rapid Assessment of Potential Ischaemic Heart Disease with CTCA (RAPID-CTCA) trial will recruit 2500 participants across about 35 hospital sites. It will be the first study to investigate the role of CTCA in the early assessment of patients with suspected or confirmed ACS who are at intermediate risk and including patients who have raised troponin measurements during initial assessment. ISRCTN19102565 . Registered on 3 October 2014. ClinicalTrials.gov: NCT02284191.

Technical innovation changes standard radiographic protocols in veterinary medicine: is it necessary to obtain two dorsoproximal-palmarodistal oblique views of the equine foot when using computerised radiography systems?

PubMed

Whitlock, J; Dixon, J; Sherlock, C; Tucker, R; Bolt, D M; Weller, R

2016-05-21

Since the 1950s, veterinary practitioners have included two separate dorsoproximal-palmarodistal oblique (DPr-PaDiO) radiographs as part of a standard series of the equine foot. One image is obtained to visualise the distal phalanx and the other to visualise the navicular bone. However, rapid development of computed radiography and digital radiography and their post-processing capabilities could mean that this practice is no longer required. The aim of this study was to determine differences in perceived image quality between DPr-PaDiO radiographs that were acquired with a computerised radiography system with exposures, centring and collimation recommended for the navicular bone versus images acquired for the distal phalanx but were subsequently manipulated post-acquisition to highlight the navicular bone. Thirty images were presented to four clinicians for quality assessment and graded using a 1-3 scale (1=textbook quality, 2=diagnostic quality, 3=non-diagnostic image). No significant difference in diagnostic quality was found between the original navicular bone images and the manipulated distal phalanx images. This finding suggests that a single DPr-PaDiO image of the distal phalanx is sufficient for an equine foot radiographic series, with appropriate post-processing and manipulation. This change in protocol will result in reduced radiographic study time and decreased patient/personnel radiation exposure. British Veterinary Association.

Artificial time constraints on the Iowa Gambling Task: the effects on behavioural performance and subjective experience.

PubMed

Bowman, Caroline H; Evans, Cathryn E Y; Turnbull, Oliver H

2005-02-01

In the last decade, the Iowa Gambling Task (IGT) has become a widely employed neuropsychological research instrument for the investigation of executive function. The task has been employed in a wide range of formats, from 'manual' procedures to more recently introduced computerised versions. Computer-based formats often require that responses on the task should be artificially delayed by a number of seconds between trials to collect skin-conductance data. Participants, however, may become frustrated when they want to select from a particular deck in the time-limited versions--so that an unintended emotional experience of frustration might well disrupt a task presumed to be reliant on emotion-based learning. We investigated the effect of the various types of Iowa Gambling Task format on performance, using three types of task: the classic manual administration, with no time limitations; a computerised administration with a 6-s enforced delay; and a control computerised version which had no time constraints. We also evaluated the subjective experience of participants on each task. There were no significant differences in performance, between formats, in behavioural terms. Subjective experience measures on the task also showed consistent effects across all three formats-with substantial, and rapidly developing, awareness of which decks were 'good' and 'bad.'

Computerised mirror therapy with Augmented Reflection Technology for early stroke rehabilitation: clinical feasibility and integration as an adjunct therapy.

PubMed

Hoermann, Simon; Ferreira Dos Santos, Luara; Morkisch, Nadine; Jettkowski, Katrin; Sillis, Moran; Devan, Hemakumar; Kanagasabai, Parimala S; Schmidt, Henning; Krüger, Jörg; Dohle, Christian; Regenbrecht, Holger; Hale, Leigh; Cutfield, Nicholas J

2017-07-01

New rehabilitation strategies for post-stroke upper limb rehabilitation employing visual stimulation show promising results, however, cost-efficient and clinically feasible ways to provide these interventions are still lacking. An integral step is to translate recent technological advances, such as in virtual and augmented reality, into therapeutic practice to improve outcomes for patients. This requires research on the adaptation of the technology for clinical use as well as on the appropriate guidelines and protocols for sustainable integration into therapeutic routines. Here, we present and evaluate a novel and affordable augmented reality system (Augmented Reflection Technology, ART) in combination with a validated mirror therapy protocol for upper limb rehabilitation after stroke. We evaluated components of the therapeutic intervention, from the patients' and the therapists' points of view in a clinical feasibility study at a rehabilitation centre. We also assessed the integration of ART as an adjunct therapy for the clinical rehabilitation of subacute patients at two different hospitals. The results showed that the combination and application of the Berlin Protocol for Mirror Therapy together with ART was feasible for clinical use. This combination was integrated into the therapeutic plan of subacute stroke patients at the two clinical locations where the second part of this research was conducted. Our findings pave the way for using technology to provide mirror therapy in clinical settings and show potential for the more effective use of inpatient time and enhanced recoveries for patients. Implications for Rehabilitation Computerised Mirror Therapy is feasible for clinical use Augmented Reflection Technology can be integrated as an adjunctive therapeutic intervention for subacute stroke patients in an inpatient setting Virtual Rehabilitation devices such as Augmented Reflection Technology have considerable potential to enhance stroke rehabilitation.

School hearing screening programme in the UK: practice and performance

PubMed Central

Fonseca, S; Forsyth, H; Neary, W

2005-01-01

Background: Paediatric audiology services and screening programmes are currently under review. Aims and Methods: To investigate current practice and performance of the school hearing screening programme (SHSP) by means of a questionnaire. Results: SHSP was found to detect previously unrecognised hearing loss at low cost. Wide variation in practice was shown, and the majority of services had no computerised system for data collection. Conclusion: There is a need for nationally agreed protocols and quality assurance procedures. PMID:15665168

PROspective MEmory Training to improve HEart failUre Self-care (PROMETHEUS): study protocol for a randomised controlled trial.

PubMed

Cameron, Jan; Rendell, Peter G; Ski, Chantal F; Kure, Christina E; McLennan, Skye N; Rose, Nathan S; Prior, David L; Thompson, David R

2015-04-29

Cognitive impairment is seen in up to three quarters of heart failure (HF) patients and has a significant negative impact on patients' health outcomes. Prospective memory, which is defined as memory to carry out future intentions, is important for functional independence in older adults and involves application of multiple cognitive processes that are often impaired in HF patients. The objective of this study is to examine the effects of prospective memory training on patients' engagement in HF self-care and health outcomes, carer strain and quality of life. The proposed study is a randomised, controlled trial in which 200 patients diagnosed with HF, and their carers will be recruited from 3 major hospitals across Melbourne. Eligible patients with HF will be randomised to receive either: 1) The Virtual Week Training Program - a computerised prospective memory (PM) training program (intervention) or 2) non-adaptive computer-based word puzzles (active control). HF patients' baseline cognitive function will be compared to a healthy control group (n = 60) living independently in the community. Patients will undergo a comprehensive assessment of PM, neuropsychological functioning, self-care, physical, and emotional functioning. Assessments will take place at baseline, 4 weeks and 12 months following intervention. Carers will complete measures assessing quality of life, strain, perceived control in the management of the patients' HF symptoms, and ratings of the patients' level of engagement in HF self-care behaviours. If the Virtual Week Training Program is effective in improving: 1) prospective memory; 2) self-care behaviours, and 3) wellbeing in HF patients, this study will enhance our understanding of impaired cognitive processes in HF and potentially is a mechanism to reduce healthcare costs. Australian New Zealand Clinical Trials Registry #366376; 27 May 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366376&isClinicalTrial=False .

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients

PubMed Central

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-01-01

Introduction Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Methods Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. Ethics and dissemination This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. PMID:28765125

Computerised cognitive behaviour therapy (cCBT) as treatment for depression in primary care (REEACT trial): large scale pragmatic randomised controlled trial

PubMed Central

Littlewood, Elizabeth; Hewitt, Catherine; Brierley, Gwen; Tharmanathan, Puvan; Araya, Ricardo; Barkham, Michael; Bower, Peter; Cooper, Cindy; Gask, Linda; Kessler, David; Lester, Helen; Lovell, Karina; Parry, Glenys; Richards, David A; Andersen, Phil; Brabyn, Sally; Knowles, Sarah; Shepherd, Charles; Tallon, Debbie; White, David

2015-01-01

Study question How effective is supported computerised cognitive behaviour therapy (cCBT) as an adjunct to usual primary care for adults with depression? Methods This was a pragmatic, multicentre, three arm, parallel randomised controlled trial with simple randomisation. Treatment allocation was not blinded. Participants were adults with symptoms of depression (score ≥10 on nine item patient health questionnaire, PHQ-9) who were randomised to receive a commercially produced cCBT programme (“Beating the Blues”) or a free to use cCBT programme (MoodGYM) in addition to usual GP care. Participants were supported and encouraged to complete the programme via weekly telephone calls. Control participants were offered usual GP care, with no constraints on the range of treatments that could be accessed. The primary outcome was severity of depression assessed with the PHQ-9 at four months. Secondary outcomes included health related quality of life (measured by SF-36) and psychological wellbeing (measured by CORE-OM) at four, 12, and 24 months and depression at 12 and 24 months. Study answer and limitations Participants offered commercial or free to use cCBT experienced no additional improvement in depression compared with usual GP care at four months (odds ratio 1.19 (95% confidence interval 0.75 to 1.88) for Beating the Blues v usual GP care; 0.98 (0.62 to 1.56) for MoodGYM v usual GP care). There was no evidence of an overall difference between either programme compared with usual GP care (0.99 (0.57 to 1.70) and 0.68 (0.42 to 1.10), respectively) at any time point. Commercially provided cCBT conferred no additional benefit over free to use cCBT or usual GP care at any follow-up point. Uptake and use of cCBT was low, despite regular telephone support. Nearly a quarter of participants (24%) had dropped out by four months. The study did not have enough power to detect small differences so these cannot be ruled out. Findings cannot be generalised to cCBT offered with a much higher level of guidance and support. What this study adds Supported cCBT does not substantially improve depression outcomes compared with usual GP care alone. In this study, neither a commercially available nor free to use computerised CBT intervention was superior to usual GP care. Funding, competing interests, data sharing Commissioned and funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project No 06/43/05). The authors have no competing interests. Requests for patient level data will be considered by the REEACT trial management group Trial registration Current Controlled Trials ISRCTN91947481. PMID:26559241

Computerised decision support in physical activity interventions: A systematic literature review.

PubMed

Triantafyllidis, Andreas; Filos, Dimitris; Claes, Jomme; Buys, Roselien; Cornelissen, Véronique; Kouidi, Evangelia; Chouvarda, Ioanna; Maglaveras, Nicos

2018-03-01

The benefits of regular physical activity for health and quality of life are unarguable. New information, sensing and communication technologies have the potential to play a critical role in computerised decision support and coaching for physical activity. We provide a literature review of recent research in the development of physical activity interventions employing computerised decision support, their feasibility and effectiveness in healthy and diseased individuals, and map out challenges and future research directions. We searched the bibliographic databases of PubMed and Scopus to identify physical activity interventions with computerised decision support utilised in a real-life context. Studies were synthesized according to the target user group, the technological format (e.g., web-based or mobile-based) and decision-support features of the intervention, the theoretical model for decision support in health behaviour change, the study design, the primary outcome, the number of participants and their engagement with the intervention, as well as the total follow-up duration. From the 24 studies included in the review, the highest percentage (n = 7, 29%) targeted sedentary healthy individuals followed by patients with prediabetes/diabetes (n = 4, 17%) or overweight individuals (n = 4, 17%). Most randomized controlled trials reported significantly positive effects of the interventions, i.e., increase in physical activity (n = 7, 100%) for 7 studies assessing physical activity measures, weight loss (n = 3, 75%) for 4 studies assessing diet, and reductions in glycosylated hemoglobin (n = 2, 66%) for 3 studies assessing glycose concentration. Accelerometers/pedometers were used in almost half of the studies (n = 11, 46%). Most adopted decision support features included personalised goal-setting (n = 16, 67%) and motivational feedback sent to the users (n = 15, 63%). Fewer adopted features were integration with electronic health records (n = 3, 13%) and alerts sent to caregivers (n = 4, 17%). Theoretical models of decision support in health behaviour to drive the development of the intervention were not reported in most studies (n = 14, 58%). Interventions employing computerised decision support have the potential to promote physical activity and result in health benefits for both diseased and healthy individuals, and help healthcare providers to monitor patients more closely. Objectively measured activity through sensing devices, integration with clinical systems used by healthcare providers and theoretical frameworks for health behaviour change need to be employed in a larger scale in future studies in order to realise the development of evidence-based computerised systems for physical activity monitoring and coaching. Copyright © 2017 Elsevier B.V. All rights reserved.

Computerised CBT for depressed adolescents: Randomised controlled trial.

PubMed

Smith, Patrick; Scott, Rebecca; Eshkevari, Ertimiss; Jatta, Fatoumata; Leigh, Eleanor; Harris, Victoria; Robinson, Alex; Abeles, Paul; Proudfoot, Judy; Verduyn, Chrissie; Yule, William

2015-10-01

Depression in adolescents is a common and impairing problem. Effective psychological therapies for depression are not accessed by most adolescents. Computerised therapy offers huge potential for improving access to treatment. To test the efficacy of Stressbusters, a Computerised-CBT (C-CBT) programme for depression in young people. Multi-site, schools-based, RCT of C-CBT compared to Waiting List, for young people (N = 112; aged 12-16) with significant symptoms of depression, using multiple-informants (adolescents, parents, teachers), with follow-up at 3 and 6 months. Relative to being on a Waiting List, C-CBT was associated with statistically significant and clinically meaningful improvements in symptoms of depression and anxiety according to adolescent self-report; and with a trend towards improvements in depression and anxiety according to parent-report. Improvements were maintained at follow-up. Treatment gains were similar for boys and girls across the participating age range. Treatment effect was partially mediated by changes in ruminative thinking. Teachers rated adolescents as having few emotional or behavioural problems, both before and after intervention. C-CBT had no detectable effect on academic attainment. In the month after intervention, young people who received C-CBT had significantly fewer absences from school than those on the Waiting List. C-CBT shows considerable promise for the treatment of mild-moderate depression in adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tiered protocol implementation improves treatment of hypoglycaemia in a neurosciences critical care and surgical intensive care unit.

PubMed

Van Berkel, Megan A; MacDermott, Jennifer; Dungan, Kathleen M; Cook, Charles H; Murphy, Claire V

2017-12-01

Although studies demonstrate techniques to limit hypoglycaemia in critically ill patients, there are limited data supporting methods to improve management of existing hypoglycaemia. Assess the impact and sustainability of a computerised, three tiered, nurse driven protocol for hypoglycaemia treatment. Retrospective pre and post protocol study. Neurosciences and surgical intensive care units at a tertiary academic medical centre. Patients with a hypoglycaemic episode were included during a pre-protocol or post-protocol implementation period. An additional six-month cohort was evaluated to assess sustainability. Fifty-four patients were included for evaluation (35 pre- and 19 post-protocol); 122 patients were included in the sustainability cohort. Hypoglycaemia treatment significantly improved in the post-protocol cohort (20% vs. 52.6%, p=0.014); with additional improvement to 79.5% in the sustainability cohort. Time to follow-up blood glucose was decreased after treatment from 122 [Q1-Q3: 46-242] minutes pre-protocol to 25 [Q1-Q3: 9-48] minutes post protocol (p<0.0001). This reduction was maintained in the sustainability cohort [median of 29min (Q1-Q3: 20-51)]. Implementation of a nurse-driven, three-tiered protocol for treatment of hypoglyacemia significantly improved treatment rates, as well as reduced time to recheck blood glucose measurement. These benefits were sustained during a six-month period after protocol implementation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combining cognitive bias modification training with motivational support in alcohol dependent outpatients: study protocol for a randomised controlled trial.

PubMed

Boffo, Marilisa; Pronk, Thomas; Wiers, Reinout W; Mannarini, Stefania

2015-02-26

Addiction research has hypothesised that automatic and reflective cognitive processes play an important role in the onset and maintenance of alcohol (ab)use, wherein automatic reactions to drug-related cues steer the drug user towards consuming before reflective processes can get over and steer towards a different behavioural response. These automatic processes include the tendency to attend and approach alcohol cues. These biases may be trained away from alcohol via computerised cognitive bias modification (CBM). The present protocol describes the design of a double-blind randomised controlled trial (RCT) testing the effectiveness of attentional bias and approach bias re-training with a 2×2 factorial design, alongside a brief motivational support (MS) program. Participants (n = 120) are adult alcohol dependent outpatients, recruited from a public health service for addiction in Italy, who have been abstinent for at least two months, and with a main diagnosis of alcohol dependence disorder. Participants are randomly assigned to one of four experimental conditions and complete 11 sessions of training after a baseline assessment. The MS takes place before each training session. Post-intervention and three-month follow-up assessments examine the change in clinical outcome variables and attentional and approach biases (measured with the Visual Probe Task and the Approach-Avoidance Task, respectively). Alcohol approach-avoidance implicit memory associations (measured with the Brief Implicit Association Test) are also evaluated at pre- and post-intervention to explore generalisation effects. Primary outcome measure is relapse rate at follow-up. Secondary outcome measures include change in cognitive biases, in alcohol-related implicit memory associations, and in the clinical variables assessed. An exploratory analysis is also planned to detect interaction effects between the CBM modules and possible moderators (interference control capacity, gender, age, number of previous detoxifications) and mediators (change in cognitive bias) of the primary outcome measure. This RCT is the first to test the effectiveness of a combined CBM intervention alongside motivational support in alcohol-dependent outpatients. The results of this study can be extremely valuable for future research in the optimisation of CBM treatment for alcohol addiction. Current Controlled Trials ISRCTN01005959 (registration date: 24 October 2013).

Evaluation and treatment of low and anxious mood in Chinese-speaking international students studying in Scotland: study protocol of a pilot randomised controlled trial.

PubMed

Zheng, Mengyi; McClay, Carrie-Anne; Wilson, Sarah; Williams, Christopher

2015-01-01

Low mood is a common mental health problem affecting up to 121 million people worldwide and is common in students, particularly international students. Cognitive behavioural therapy (CBT) is known to be effective as a treatment for low mood and anxiety when delivered one to one by an expert practitioner, however this can be expensive and many services have waiting lists and delayed access. A range of additional ways of increasing access to services includes the offer of online courses such as computerised CBT as a possible additional pathway for care. This project aims to test the feasibility of a pilot randomised controlled trial of an online CBT-based life skills course with Chinese-speaking international students experiencing low mood and anxiety. Chinese-speaking international students with symptoms of low mood and/or anxiety will be recruited from the University of Glasgow, Scotland. Participants will be remotely randomised to receive either immediate access (IA) or delayed access (DA) to a guided/supported online CBT-based life skills package, the "Living Life" package (Chinese version). Participants will be randomly assigned to IA or DA to the intervention. The primary end point will be at 3 months when the delayed group will be offered the intervention. Levels of depression, anxiety, social functioning and satisfaction will be assessed. This pilot study will test the trial design, ability to recruit, gather completed questionnaires, test drop-out rates and investigate completion and acceptability of the package. The study aims to reduce uncertainties about the delivery of a future substantive study and will also inform a sample size calculation for that subsequent substantive randomised controlled trial (RCT) which will be carried out to determine the effectiveness of the online package in improving low mood and anxiety in the Chinese-speaking student population. Current Controlled Trials ISRCTN30816908.

Training and transfer effects of N-back training for brain-injured and healthy subjects.

PubMed

Lindeløv, Jonas Kristoffer; Dall, Jonas Olsen; Kristensen, Casper Daniel; Aagesen, Marie Holt; Olsen, Stine Almgren; Snuggerud, Therese Ruud; Sikorska, Anna

2016-10-01

Working memory impairments are prevalent among patients with acquired brain injury (ABI). Computerised training targeting working memory has been researched extensively using samples from healthy populations but this field remains isolated from similar research in ABI patients. We report the results of an actively controlled randomised controlled trial in which 17 patients and 18 healthy subjects completed training on an N-back task. The healthy group had superior improvements on both training tasks (SMD = 6.1 and 3.3) whereas the ABI group improved much less (SMD = 0.5 and 1.1). Neither group demonstrated transfer to untrained tasks. We conclude that computerised training facilitates improvement of specific skills rather than high-level cognition in healthy and ABI subjects alike. The acquisition of these specific skills seems to be impaired by brain injury. The most effective use of computer-based cognitive training may be to make the task resemble the targeted behaviour(s) closely in order to exploit the stimulus-specificity of learning.

A randomised controlled trial of an intervention to increase the implementation of a healthy canteen policy in Australian primary schools: study protocol.

PubMed

Wolfenden, Luke; Nathan, Nicole; Williams, Christopher M; Delaney, Tessa; Reilly, Kathryn L; Freund, Megan; Gillham, Karen; Sutherland, Rachel; Bell, Andrew C; Campbell, Libby; Yoong, Serene; Wyse, Rebecca; Janssen, Lisa M; Preece, Sarah; Asmar, Melanie; Wiggers, John

2014-10-11

The implementation of healthy school canteen policies has been recommended as a strategy to help prevent unhealthy eating and excessive weight gain. Internationally, research suggests that schools often fail to implement practices consistent with healthy school canteen policies. Without a population wide implementation, the potential benefits of these policies will not be realised. The aim of this trial is to assess the effectiveness of an implementation intervention in increasing school canteen practices consistent with a healthy canteen policy of the New South Wales (NSW), Australia, government known as the 'Fresh Tastes @ School NSW Healthy School Canteen Strategy'. The parallel randomised trial will be conducted in 70 primary schools located in the Hunter region of New South Wales, Australia. Schools will be eligible to participate if they are not currently meeting key components of the healthy canteen policy. Schools will be randomly allocated after baseline data collection in a 1:1 ratio to either an intervention or control group using a computerised random number function in Microsoft Excel. Thirty-five schools will be selected to receive a multi-component intervention including implementation support from research staff, staff training, resources, recognition and incentives, consensus and leadership strategies, follow-up support and implementation feedback. The 35 schools allocated to the control group will not receive any intervention support as part of the research trial. The primary outcome measures will be i) the proportion of schools with a canteen menu that does not contain foods or beverages restricted from regular sale ('red' and 'banned' items) and ii) the proportion of schools where healthy canteen items ('green' items) represent the majority (>50%) of products listed on the menu. Outcome data will be collected via a comprehensive menu audit, conducted by dietitians blind to group allocation. Intervention effectiveness will be assessed using logistic regression models adjusting for baseline values. The proposed trial will represent a novel contribution to the literature, being the first randomised trial internationally to examine the effectiveness of an intervention to facilitate implementation of a healthy canteen policy. Australian New Zealand Clinical Trials Registry ACTRN12613000311752.

Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial.

PubMed

2017-04-29

Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes. In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks' gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152. Between Jan 6, 2010, and Aug 31, 2013, 47 062 women were randomly assigned (23 515 in the decision-support group and 23 547 in the no-decision-support group) and 46 042 were analysed (22 987 in the decision-support group and 23 055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups-172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82-1·25). At 2 years, no significant differences were noted in terms of developmental assessment. Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal monitoring in labour does not improve clinical outcomes for mothers or babies. National Institute for Health Research. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Cyborg practices: call-handlers and computerised decision support systems in urgent and emergency care.

PubMed

Pope, Catherine; Halford, Susan; Turnbull, Joanne; Prichard, Jane

2014-06-01

This article draws on data collected during a 2-year project examining the deployment of a computerised decision support system. This computerised decision support system was designed to be used by non-clinical staff for dealing with calls to emergency (999) and urgent care (out-of-hours) services. One of the promises of computerised decisions support technologies is that they can 'hold' vast amounts of sophisticated clinical knowledge and combine it with decision algorithms to enable standardised decision-making by non-clinical (clerical) staff. This article draws on our ethnographic study of this computerised decision support system in use, and we use our analysis to question the 'automated' vision of decision-making in healthcare call-handling. We show that embodied and experiential (human) expertise remains central and highly salient in this work, and we propose that the deployment of the computerised decision support system creates something new, that this conjunction of computer and human creates a cyborg practice.

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients.

PubMed

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-08-01

Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

ACP Best Practice No 166

PubMed Central

Cruickshank, A

2001-01-01

After subarachnoid haemorrhage (SAH), cerebral angiography is usually performed to establish a site of bleeding, which may then be treated surgically to prevent a potentially catastrophic re-bleed. The investigation of choice in the diagnosis of SAH is computerised tomography (CT). However, because CT can miss some patients with SAH, cerebrospinal fluid (CSF) spectrophotometry should be performed in those patients with negative or equivocal CT scans or those who have presented several days after the suspected bleed. Spectrophotometry should aim to detect the presence of both oxyhaemoglobin and bilirubin because either one or both of these pigments may contribute to xanthochromia following SAH. CSF supernatant is scanned using a double beam spectrophotometer at wavelengths between 350 nm and 650 nm. Oxyhaemoglobin alone produces an absorption peak at 413–415 nm, bilirubin alone produces a broad peak at 450–460 nm, and bilirubin together with oxyhaemoglobin produce a shoulder at 450–460 nm on the downslope of the oxyhaemoglobin peak. To minimise the frequency of false positive and false negative results, a protocol has been developed, which is described. Key Words: subarachnoid haemorrhage • computerised tomography • cerebrospinal fluid • spectrophotometry • oxyhaemoglobin • bilirubin • xanthochromia PMID:11684714

The Brain Games study: protocol for a randomised controlled trial of computerised cognitive training for preventing mental illness in adolescents with high-risk personality styles

PubMed Central

Mewton, Louise; Hodge, Antoinette; Gates, Nicola; Visontay, Rachel; Teesson, Maree

2017-01-01

Introduction A broad range of mental disorders are now understood as aberrations of normal adolescent brain development. In both adolescents and adults, executive dysfunction has been implicated across a range of mental illnesses, and enhancing executive functioning may prove to be a useful prevention strategy for adolescents at risk for a range of psychopathology. Methods and analysis This study will consist of a double-blind, randomised controlled trial with a 12-month follow-up period. Participants will consist of 200 people aged 16–24 years who are at risk for a range of mental disorders based on personality risk factors, but have not experienced a lifetime mental illness as determined by a structured diagnostic interview. Participants will be randomly allocated to either an intervention group who complete an online cognitive training programme specifically targeting executive functioning ability or a control group who complete an online cognitive training programme that has limited executive functioning training potential. Superiority of the executive functioning training programme compared with the control training programme will be assessed at baseline, post-training and at 3-month, 6-month and 12-month follow-up. All assessments will be conducted online. The primary outcome of the study will be general psychopathology as measured by the Strengths and Difficulties Questionnaire. Secondary outcomes will include executive functioning ability, day-to-day functioning and alcohol consumption. All analyses will be undertaken using mixed-model repeated measures analysis of variance with planned contrasts. Ethics and dissemination Ethics approval has been obtained from the University of New South Wales Human Research Ethics Committee (HC15094). Results of the trial immediately post-treatment and at 12 months follow-up will be submitted for publication in peer-reviewed journals. Trial registration number ACTRN12616000127404; Pre-results. PMID:28951415

From hospital information system components to the medical record and clinical guidelines & protocols.

PubMed

Veloso, M; Estevão, N; Ferreira, P; Rodrigues, R; Costa, C T; Barahona, P

1997-01-01

This paper introduces an ongoing project towards the development of a new generation HIS, aiming at the integration of clinical and administrative information within a common framework. Its design incorporates explicit knowledge about domain objects and professional activities to be processed by the system together with related knowledge management services and act management services. The paper presents the conceptual model of the proposed HIS architecture, that supports a rich and fully integrated patient data model, enabling the implementation of a dynamic electronic patient record tightly coupled with computerised guideline knowledge bases.

Immunisation registers in Italy: a patchwork of computerisation.

PubMed

Alfonsi, V; D'Ancona, F; Rota, M C; Giambi, C; Ranghiasci, A; Iannazzo, S

2012-04-26

In Italy, the 21 regional health authorities are in charge of organising and implementing their own vaccination strategy, based on the national vaccine plan. Immunisation coverage varies greatly among the regions for certain vaccines. Efforts to increase childhood immunisation coverage have included initiatives to develop and implement computerised immunisation registers in as many regions as possible. We undertook a cross-sectional online survey in July 2011 to provide an updated picture of the use, heterogeneity and main functions of different computerised immunisation registers used in the Italian regions and to understand the flow of information from local health units to the regional authorities and to the Ministry of Health. Comparing current data with those obtained in 2007, a substantial improvement is evident. A total of 15 regions are fully computerised (previously nine), with 83% of local health units equipped with a computerised register (previously 70%). Eight of the 15 fully computerised regions use the same software, simplifying data sharing. Only four regions are able to obtain data in real time from local health units. Despite the progress made, the capacity to monitor vaccination coverage and to exchange data appears still limited.

Does post-exercise massage treatment reduce delayed onset muscle soreness? A systematic review

PubMed Central

Ernst, E.

1998-01-01

BACKGROUND: Delayed onset muscle soreness (DOMS) is a frequent problem after unaccustomed exercise. No universally accepted treatment exists. Massage therapy is often recommended for this condition but uncertainty exists about its effectiveness. AIM: To determine whether post-exercise massage alleviates the symptoms of DOMS after a bout of strenuous exercise. METHOD: Various computerised literature searches were carried out and located seven controlled trials. RESULTS: Most of the trials were burdened with serious methodological flaws, and their results are far from uniform. However, most suggest that post-exercise massage may alleviate symptoms of DOMS. CONCLUSIONS: Massage therapy may be a promising treatment for DOMS. Definitive studies are warranted. 


 PMID:9773168

Computerised cognitive–behavioural therapy for depression in adolescents: feasibility results and 4-month outcomes of a UK randomised controlled trial

PubMed Central

Wright, Barry; Tindall, Lucy; Littlewood, Elizabeth; Allgar, Victoria; Abeles, Paul; Trépel, Dominic; Ali, Shehzad

2017-01-01

Objectives Computer-administered cognitive–behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. Design Single centre RCT feasibility study. Setting The trial was run within community and clinical settings in York, UK. Participants Adolescents (aged 12–18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. Interventions An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). Primary and secondary outcome measures Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. Results From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. Conclusions With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. Trial registration number ISRCTN31219579. PMID:28132000

Review and publication of protocol submissions to Trials - what have we learned in 10 years?

PubMed

Li, Tianjing; Boutron, Isabelle; Al-Shahi Salman, Rustam; Cobo, Erik; Flemyng, Ella; Grimshaw, Jeremy M; Altman, Douglas G

2016-12-16

Trials has 10 years of experience in providing open access publication of protocols for randomised controlled trials. In this editorial, the senior editors and editors-in-chief of Trials discuss editorial issues regarding managing trial protocol submissions, including the content and format of the protocol, timing of submission, approaches to tracking protocol amendments, and the purpose of peer reviewing a protocol submission. With the clarification and guidance provided, we hope we can make the process of publishing trial protocols more efficient and useful to trial investigators and readers.

Attitudes of nursing staff towards computerisation: a case of two hospitals in Nairobi, Kenya

PubMed Central

2014-01-01

Background The health sector is faced with constant changes as new approaches to tackle illnesses are unveiled through research. Information, communication and technology have greatly transformed healthcare practice the world over. Nursing is continually exposed to a variety of changes. Variables including age, educational level, years worked in nursing, computer knowledge and experience have been found to influence the attitudes of nurses towards computerisation. The purpose of the study was to determine the attitudes of nurses towards the use of computers and the factors that influence these attitudes. Methods This cross sectional descriptive study was conducted among staff nurses working at one public hospital (Kenyatta National Hospital, (KNH) and one private hospital (Aga Khan University Hospital (AKUH). A convenience sample of 200 nurses filled the questionnaires. Data was collected using the modified Nurses’ Attitudes Towards Computerisation (NATC) questionnaire. Results Nurses had a favorable attitude towards computerisation. Non-users had a significantly higher attitude score compared to the users (p = 0.0274). Statistically significant associations were observed with age (p = 0.039), level of education (p = 0.025), duration of exposure to computers (p = 0.025) and attitudes towards computerisation. Conclusion Generally, nurses have positive attitudes towards computerisation. This information is important for the planning and implementation of computerisation in the hospital as suggested in other studies. PMID:24774008

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2015-12-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

PubMed Central

Chan, An-Wen; Tetzlaff, Jennifer M.; Altman, Douglas G.; Laupacis, Andreas; Gøtzsche, Peter C.; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A.; Doré, Caroline J.; Parulekar, Wendy R.; Summerskill, William S.M.; Groves, Trish; Schulz, Kenneth F.; Sox, Harold C.; Rockhold, Frank W.; Rennie, Drummond; Moher, David

2016-01-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders. PMID:23295957

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Doré, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2013-02-05

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Aromatherapy: a systematic review.

PubMed

Cooke, B; Ernst, E

2000-06-01

Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials.

Aromatherapy: a systematic review.

PubMed Central

Cooke, B; Ernst, E

2000-01-01

Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials. PMID:10962794

Computerised sepsis protocol management. Description of an early warning system.

PubMed

de Dios, Begoña; Borges, Marcio; Smith, Timothy D; Del Castillo, Alberto; Socias, Antonia; Gutiérrez, Leticia; Nicolás, Jordi; Lladó, Bartolomé; Roche, Jose A; Díaz, Maria P; Lladó, Yolanda

2018-02-01

New strategies need to be developed for the early recognition and rapid response for the management of sepsis. To achieve this purpose, the Multidisciplinary Sepsis Team (MST) developed the Computerised Sepsis Protocol Management (PIMIS). The aim of this study was to evaluate the convenience of using PIMIS, as well as the activity of the MST. An analysis was performed on the data collected from solicited MST consultations (direct activation of PIMIS by attending physician or telephone request) and unsolicited ones (by referral from the microbiology laboratory or an automatic referral via the hospital vital signs recording software [SIDCV]), as well as the hospital department, source of infection, treatment recommendation, and acceptance of this. Of the 1,581 first consultations, 65.1% were solicited consultations (84.1% activation of PIMIS and 15.9% by telephone). The majority of unsolicited consultations were generated by the microbiology laboratory (95.2%), and 4.8% from the SIDCV. Referral from solicited consultations were generated sooner (5.63days vs 8.47days; P<.001) and came from clinical specialties rather than from the surgical ward (73.0% vs 39.1%; P<.001). A recommendation was made for antimicrobial prescription change in 32% of first consultations. The treating physician accepted 78.1% of recommendations. The high rate of solicited consultations and acceptance of recommended prescription changes suggest that a MST is seen as a helpful resource, and that PIMIS software is perceived to be useful and convenient to use, as it is the main source of referral. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

The Cognitive Remediation in Bipolar (CRiB) pilot study: study protocol for a randomised controlled trial.

PubMed

Strawbridge, Rebecca; Fish, Jessica; Halari, Rozmin; Hodsoll, John; Reeder, Clare; Macritchie, Karine; McCrone, Paul; Wykes, Til; Young, Allan H

2016-07-29

People with bipolar disorder often show difficulties with cognitive functioning, and though these difficulties are identified as important targets for intervention, few treatment options are available. Preliminary evidence suggests that cognitive remediation therapy (a psychological treatment proven beneficial for people diagnosed as having schizophrenia) is helpful for people with bipolar disorders. We are conducting a pilot trial to determine whether individual, computerised, cognitive remediation therapy (CRT) for people with bipolar disorder 1) increases cognitive function; 2) improves global functioning, goal attainment and mood symptoms; 3) is acceptable and feasible for participants; and 4) can be addressed in a comprehensive, larger, randomised, controlled trial. The study is designed as a two-arm, randomised, controlled trial comparing cognitive remediation therapy with treatment-as-usual (TAU) for euthymic bipolar patients. Participants are eligible to take part if aged between 18 and 65 with a diagnosis of bipolar disorder (type I) and currently in euthymic state, and no neurological, substance or personality disorder diagnoses. Sixty participants will be recruited (mainly through secondary and tertiary care) and will be block-randomised to receive either treatment-as-usual alone or in addition to a 12-week course of cognitive remediation therapy totalling 20-40 therapy hours. The intervention will comprise regular sessions with a therapist and computer-based training. Research assessments will take place before and after the intervention period and at a 12-week follow-up, and will include evaluation of neuropsychological, symptom-related, demographic and social factors, as well as collecting qualitative data regarding CRT expectations and satisfaction. Intention-to-treat analyses will examine the efficacy of cognitive remediation therapy primarily on cognition and additionally on functioning, quality of life and mood symptoms. Furthermore, we will examine the acceptability of CRT and undertake a preliminary health economics analysis to ascertain the cost of delivering the intervention. The results of this trial will provide valuable information about whether cognitive remediation therapy may be beneficial for people diagnosed with bipolar disorder in a euthymic state. ISRCTN registry, ISRCTN32290525 . Registered on 2 March 2016.

[Correlation between iridology and general pathology].

PubMed

Demea, Sorina

2002-01-01

The research proposal is to evaluate the association between certain irian signs and general pathology of studied patients. There were studied 57 hospitalized patients; there was taken over all their iris images, which were analyzed through iridological protocols; in the same time the pathology of these patients was noted from their records in the hospital, concordant with the clinical diagnosis; all these information were included in a database for a computerised processing. The correlations resulted from, shows a high connection between the irian constitution establish through iridological criteria and the existent pathology. Iris examination can be very useful for diagnosis of a certain general pathology, in a holistic approach of the patient.

Computerised cognitive-behavioural therapy for depression in adolescents: feasibility results and 4-month outcomes of a UK randomised controlled trial.

PubMed

Wright, Barry; Tindall, Lucy; Littlewood, Elizabeth; Allgar, Victoria; Abeles, Paul; Trépel, Dominic; Ali, Shehzad

2017-01-27

Computer-administered cognitive-behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. Single centre RCT feasibility study. The trial was run within community and clinical settings in York, UK. Adolescents (aged 12-18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. ISRCTN31219579. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory.

PubMed

Hróbjartsson, Asbjørn; Pildal, Julie; Chan, An-Wen; Haahr, Mette T; Altman, Douglas G; Gøtzsche, Peter C

2009-09-01

To compare the reporting on blinding in protocols and articles describing randomized controlled trials. We studied 73 protocols of trials approved by the scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding publications. Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., "open" vs. "double blind"). The proportion of "double-blind" trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients, health care providers, and data collectors had been blinded. In 4 of the 52 trials (7%), the protocols clarified that all three key trial persons had been blinded. The reporting on blinding in both trial protocols and publications is often inadequate. We suggest developing international guidelines for the reporting of trial protocols and public access to protocols.

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

PubMed

Perlmutter, A S; Tran, V-T; Dechartres, A; Ravaud, P

2017-04-01

Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The Brain Games study: protocol for a randomised controlled trial of computerised cognitive training for preventing mental illness in adolescents with high-risk personality styles.

PubMed

Mewton, Louise; Hodge, Antoinette; Gates, Nicola; Visontay, Rachel; Teesson, Maree

2017-09-25

A broad range of mental disorders are now understood as aberrations of normal adolescent brain development. In both adolescents and adults, executive dysfunction has been implicated across a range of mental illnesses, and enhancing executive functioning may prove to be a useful prevention strategy for adolescents at risk for a range of psychopathology. This study will consist of a double-blind, randomised controlled trial with a 12-month follow-up period. Participants will consist of 200 people aged 16-24 years who are at risk for a range of mental disorders based on personality risk factors, but have not experienced a lifetime mental illness as determined by a structured diagnostic interview. Participants will be randomly allocated to either an intervention group who complete an online cognitive training programme specifically targeting executive functioning ability or a control group who complete an online cognitive training programme that has limited executive functioning training potential. Superiority of the executive functioning training programme compared with the control training programme will be assessed at baseline, post-training and at 3-month, 6-month and 12-month follow-up. All assessments will be conducted online. The primary outcome of the study will be general psychopathology as measured by the Strengths and Difficulties Questionnaire. Secondary outcomes will include executive functioning ability, day-to-day functioning and alcohol consumption. All analyses will be undertaken using mixed-model repeated measures analysis of variance with planned contrasts. Ethics approval has been obtained from the University of New South Wales Human Research Ethics Committee (HC15094). Results of the trial immediately post-treatment and at 12 months follow-up will be submitted for publication in peer-reviewed journals. ACTRN12616000127404; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected attention deficit hyperactivity disorder: single-blind randomised controlled trial.

PubMed

Hollis, Chris; Hall, Charlotte L; Guo, Boliang; James, Marilyn; Boadu, Janet; Groom, Madeleine J; Brown, Nikki; Kaylor-Hughes, Catherine; Moldavsky, Maria; Valentine, Althea Z; Walker, Gemma M; Daley, David; Sayal, Kapil; Morriss, Richard

2018-04-26

Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04-2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77-0.93), increased clinicians' confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09-2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as 'cost neutral'. QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Post-trial period surveillance for randomised controlled cardiovascular studies: submitted protocols, consent forms and the role of the ethics board.

PubMed

Zia, Mohammad I; Heslegrave, Ronald; Newton, Gary E

2011-12-01

The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. An observational study of protocols of randomised trials of chronic therapies for cardiac conditions, approved by the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised.

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials

PubMed Central

Tetzlaff, Jennifer M; Gøtzsche, Peter C; Altman, Douglas G; Mann, Howard; Berlin, Jesse A; Dickersin, Kay; Hróbjartsson, Asbjørn; Schulz, Kenneth F; Parulekar, Wendy R; Krleža-Jerić, Karmela; Laupacis, Andreas; Moher, David

2013-01-01

High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders. PMID:23303884

SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Gøtzsche, Peter C; Altman, Douglas G; Mann, Howard; Berlin, Jesse A; Dickersin, Kay; Hróbjartsson, Asbjørn; Schulz, Kenneth F; Parulekar, Wendy R; Krleza-Jeric, Karmela; Laupacis, Andreas; Moher, David

2013-01-08

High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

Volunteer involvement in the support of self-managed computerised aphasia treatment: The volunteer perspective.

PubMed

Palmer, Rebecca; Enderby, Pam

2016-10-01

The speech-language pathology profession has explored a number of approaches to support efficient delivery of interventions for people with stroke-induced aphasia. This study aimed to explore the role of volunteers in supporting self-managed practice of computerised language exercises. A qualitative interview study of the volunteer support role was carried out alongside a pilot randomised controlled trial of computer aphasia therapy. Patients with aphasia practised computer exercises tailored for them by a speech-language pathologist at home regularly for 5 months. Eight of the volunteers who supported the intervention took part in semi-structured interviews. Interviews were audio recorded, transcribed verbatim and analysed thematically. Emergent themes included: training and support requirements; perception of the volunteer role; challenges facing the volunteer, in general and specifically related to supporting computer therapy exercises. The authors concluded that volunteers helped to motivate patients to practise their computer therapy exercises and also provided support to the carers. Training and ongoing structured support of therapy activity and conduct is required from a trained speech-language pathologist to ensure the successful involvement of volunteers supporting impairment-based computer exercises in patients' own homes.

A randomised controlled trial of oral chloral hydrate vs. intranasal dexmedetomidine before computerised tomography in children.

PubMed

Yuen, V M; Li, B L; Cheuk, D K; Leung, M K M; Hui, T W C; Wong, I C; Lam, W W; Choi, S W; Irwin, M G

2017-10-01

Chloral hydrate is commonly used to sedate children for painless procedures. Children may recover more quickly after sedation with dexmedetomidine, which has a shorter half-life. We randomly allocated 196 children to chloral hydrate syrup 50 mg.kg -1 and intranasal saline spray, or placebo syrup and intranasal dexmedetomidine spray 3 μg.kg -1 , 30 min before computerised tomography studies. More children resisted or cried after drinking chloral hydrate syrup than placebo syrup, 72 of 107 (67%) vs. 42 of 87 (48%), p = 0.009, but there was no difference after intranasal saline vs. dexmedetomidine, 49 of 107 (46%) vs. 40 of 87 (46%), p = 0.98. Sedation was satisfactory in 81 of 107 (76%) children after chloral hydrate and 64 of 87 (74%) children after dexmedetomidine, p = 0.74. Of the 173 children followed up for at least 4 h after discharge, 38 of 97 (39%) had recovered normal function after chloral hydrate and 32 of 76 (42%) after dexmedetomidine, p = 0.76. Six children vomited after chloral hydrate syrup and placebo spray vs. none after placebo syrup and dexmedetomidine spray, p = 0.03. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Protocol for the PINCER trial: a cluster randomised trial comparing the effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

PubMed Central

Avery, Anthony J; Rodgers, Sarah; Cantrill, Judith A; Armstrong, Sarah; Elliott, Rachel; Howard, Rachel; Kendrick, Denise; Morris, Caroline J; Murray, Scott A; Prescott, Robin J; Cresswell, Kathrin; Sheikh, Aziz

2009-01-01

Background Medication errors are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. Methods Research subject group: "At-risk" patients registered with computerised general practices in two geographical regions in England. Design: Parallel group pragmatic cluster randomised trial. Interventions: Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. Primary outcome measures: The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs - with a computer-recorded diagnosis of asthma being prescribed beta-blockers - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. Secondary outcome measures; These relate to a number of other examples of potentially hazardous prescribing and medicines management. Economic analysis: An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. Qualitative analysis: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. Sample size: 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. Discussion At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken. Trial registration Current controlled trials ISRCTN21785299 PMID:19409095

Assessing the detection, reporting and investigation of adverse events in clinical trial protocols implemented in Cameroon: a documentary review of clinical trial protocols.

PubMed

Ebile, Akoh Walter; Ateudjieu, Jerome; Yakum, Martin Ndinakie; Djuidje, Marceline Ngounoue; Watcho, Pierre

2015-09-29

International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee.

Systematic Evaluation of the Patient-Reported Outcome (PRO) Content of Clinical Trial Protocols

PubMed Central

Kyte, Derek; Duffy, Helen; Fletcher, Benjamin; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; King, Madeleine; Draper, Heather; Ives, Jonathan; Brundage, Michael; Blazeby, Jane; Calvert, Melanie

2014-01-01

Background Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols. Methods and Findings We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the ‘Standard Protocol Items: Recommendations for Interventional Trials’ (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16–41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4–18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively ‘complete’ using SPIRIT were still likely to have omitted a large proportion of PRO checklist items. Conclusions The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully addressed by the current SPIRIT statement. We therefore advocate the development of consensus-based supplementary guidelines, aimed at improving the completeness and quality of PRO content in clinical trial protocols. PMID:25333349

Internet-based support for self-management strategies for people with COPD-protocol for a controlled pragmatic pilot trial of effectiveness and a process evaluation in primary healthcare.

PubMed

Nyberg, André; Wadell, Karin; Lindgren, Helena; Tistad, Malin

2017-08-01

The use of adequate self-management strategies for people with chronic obstructive pulmonary disease (COPD) reduces healthcare use, improves health-related quality of life (HRQoL) and recovery after acute exacerbations. However, not many people with COPD receive support that promotes the use of such strategies and therefore new methods to facilitate and promote the use of self-management strategies are highly warranted. This pilot trial aims to evaluate the feasibility of the study design and study procedures considering effectiveness of the novel intervention, the COPD-web. METHODS AND ANALYSIS: The overall design is a pragmatic controlled pilot trial with preassessments and postassessments and a parallel process evaluation. Patients with the diagnosis of COPD will be eligible for the study. The intervention group will be recruited when visiting one of the six participating primary care units in Sweden. The control group will be identified from the unit's computerised registers. The intervention, the COPD-web, is an interactive web page with two sections; one directed at people with COPD and one at healthcare professionals. The sections aim to support patients' self-management skills-and to facilitate the provision of support for self-management strategies, respectively. Effectiveness with regard to patients' symptoms, HRQoL, knowledge of and readiness for COPD-related self-management, health literacy, self-efficacy for physical activity and time spent in physical activity and time being sedentary, and further, healthcare professionals' knowledge of and readiness to support COPD-related self-management strategies will be assessed using questionnaires at 3 and 12 months. The process evaluation will include observations and interviews. Ethical approval has been obtained. Findings will be presented at conferences, submitted for publication in peer-reviewed publications and presented to the involved healthcare professionals, patients and to patient organisations. ClinicalTrials.gov: NCT02696187. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

PubMed

Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

2016-12-07

It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

Investigating pulmonary embolism in the emergency department with lower limb plethysmography: the Manchester Investigation of Pulmonary Embolism Diagnosis (MIOPED) study

PubMed Central

Hogg, K; Dawson, D; Mackway‐Jones, K

2006-01-01

Objectives To measure the diagnostic accuracy of computerised strain gauge plethysmography in the diagnosis of pulmonary embolism (PE). Methods Two researchers prospectively recruited 425 patients with pleuritic chest pain presenting to the emergency department (ED). Lower limb computerised strain gauge plethysmography was performed in the ED. All patients underwent an independent reference standard diagnostic algorithm to establish the presence or absence of PE. A low modified Wells' clinical probability combined with a normal D‐dimer excluded PE. All others required diagnostic imaging with PIOPED interpreted ventilation perfusion scanning and/or computerised tomography (CT) pulmonary angiography. Patients with a nondiagnostic CT had digital subtraction pulmonary angiography. All patients were followed up clinically for 3 months. Results The sensitivity of computerised strain gauge plethysmography was 33.3% (95% confidence interval (CI) 16.3 to 56.2%) and specificity 64.1% (95% CI 59.0 to 68.8%). The negative likelihood ratio was 1.04 (95% CI 0.68 to 1.33) and positive likelihood ratio 0.93 (95% CI 0.45 to 1.60). Conclusions Lower limb computerised strain gauge plethysmography does not aid in the diagnosis of PE. PMID:16439734

Support and Assessment for Fall Emergency Referrals (SAFER 1): Cluster Randomised Trial of Computerised Clinical Decision Support for Paramedics

PubMed Central

Snooks, Helen Anne; Carter, Ben; Dale, Jeremy; Foster, Theresa; Humphreys, Ioan; Logan, Philippa Anne; Lyons, Ronan Anthony; Mason, Suzanne Margaret; Phillips, Ceri James; Sanchez, Antonio; Wani, Mushtaq; Watkins, Alan; Wells, Bridget Elizabeth; Whitfield, Richard; Russell, Ian Trevor

2014-01-01

Objective To evaluate effectiveness, safety and cost-effectiveness of Computerised Clinical Decision Support (CCDS) for paramedics attending older people who fall. Design Cluster trial randomised by paramedic; modelling. Setting 13 ambulance stations in two UK emergency ambulance services. Participants 42 of 409 eligible paramedics, who attended 779 older patients for a reported fall. Interventions Intervention paramedics received CCDS on Tablet computers to guide patient care. Control paramedics provided care as usual. One service had already installed electronic data capture. Main Outcome Measures Effectiveness: patients referred to falls service, patient reported quality of life and satisfaction, processes of care. Safety Further emergency contacts or death within one month. Cost-Effectiveness Costs and quality of life. We used findings from published Community Falls Prevention Trial to model cost-effectiveness. Results 17 intervention paramedics used CCDS for 54 (12.4%) of 436 participants. They referred 42 (9.6%) to falls services, compared with 17 (5.0%) of 343 participants seen by 19 control paramedics [Odds ratio (OR) 2.04, 95% CI 1.12 to 3.72]. No adverse events were related to the intervention. Non-significant differences between groups included: subsequent emergency contacts (34.6% versus 29.1%; OR 1.27, 95% CI 0.93 to 1.72); quality of life (mean SF12 differences: MCS −0.74, 95% CI −2.83 to +1.28; PCS −0.13, 95% CI −1.65 to +1.39) and non-conveyance (42.0% versus 36.7%; OR 1.13, 95% CI 0.84 to 1.52). However ambulance job cycle time was 8.9 minutes longer for intervention patients (95% CI 2.3 to 15.3). Average net cost of implementing CCDS was £208 per patient with existing electronic data capture, and £308 without. Modelling estimated cost per quality-adjusted life-year at £15,000 with existing electronic data capture; and £22,200 without. Conclusions Intervention paramedics referred twice as many participants to falls services with no difference in safety. CCDS is potentially cost-effective, especially with existing electronic data capture. Trial Registration ISRCTN Register ISRCTN10538608 PMID:25216281

[The electronic health record: computerised provider order entry and the electronic instruction document as new functionalities].

PubMed

Derikx, Joep P M; Erdkamp, Frans L G; Hoofwijk, A G M

2013-01-01

An electronic health record (EHR) should provide 4 key functionalities: (a) documenting patient data; (b) facilitating computerised provider order entry; (c) displaying the results of diagnostic research; and (d) providing support for healthcare providers in the clinical decision-making process.- Computerised provider order entry into the EHR enables the electronic receipt and transfer of orders to ancillary departments, which can take the place of handwritten orders.- By classifying the computer provider order entries according to disorders, digital care pathways can be created. Such care pathways could result in faster and improved diagnostics.- Communicating by means of an electronic instruction document that is linked to a computerised provider order entry facilitates the provision of healthcare in a safer, more efficient and auditable manner.- The implementation of a full-scale EHR has been delayed as a result of economic, technical and legal barriers, as well as some resistance by physicians.

The Robinson Protocol: a treadmill anaerobic performance test.

PubMed

Robinson, Ellyn M; Graham, Louise B; Headley, Samuel A

2004-08-01

The current investigation was designed to further examine the reliability of the Robinson protocol, which is a run-to-exhaustion treadmill test. Robinson (10) originally examined this protocol with 5 subjects. The significance of the initial exploratory study was the impetus for expanding the study to examine the reliability of the protocol with a larger sample. Fifteen male subjects participated in 3 trial runs on the treadmill. The first trial was a modified McConnell (7) test to determine the aerobic capacity of each subject. The second and third trials were identical Robinson protocols (10). The first trial run mean, in seconds (262.04 +/- 74.50), was not significantly different from the second trial run mean (257.30 +/- 72.65), p = 0.526 (2 tailed). As expected, trial 1 and trial 2 were highly correlated (intraclass) (r = 0.927, p < 0.001). These results provide additional support for the hypothesis that the Robinson protocol with a greater subject pool is a reliable protocol that can be used in research studies interested in examining various physiological interventions or anaerobic training.

Protecting intellectual property associated with Canadian academic clinical trials - approaches and impact

PubMed Central

2012-01-01

Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation. The ‘open access’ approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism. The ‘restricted access’ approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who ‘needs to know’ about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial. It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results. PMID:23270486

Protecting intellectual property associated with Canadian academic clinical trials--approaches and impact.

PubMed

Ross, Sue; Magee, Laura; Walker, Mark; Wood, Stephen

2012-12-27

Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation. The 'open access' approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism. The 'restricted access' approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who 'needs to know' about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial. It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results.

Digital IAPT: the effectiveness & cost-effectiveness of internet-delivered interventions for depression and anxiety disorders in the Improving Access to Psychological Therapies programme: study protocol for a randomised control trial.

PubMed

Richards, Derek; Duffy, Daniel; Blackburn, Brid; Earley, Caroline; Enrique, Angel; Palacios, Jorge; Franklin, Matthew; Clarke, Gabriella; Sollesse, Sarah; Connell, Sarah; Timulak, Ladislav

2018-03-02

Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered).

Electronic Clinical Trial Protocol Distribution via the World-Wide Web

PubMed Central

Afrin, Lawrence B.; Kuppuswamy, Valarmathi; Slater, Barbara; Stuart, Robert K.

1997-01-01

Clinical trials today typically are inefficient, paper-based operations. Poor community physician awareness of available trials and difficult referral mechanisms also contribute to poor accrual. The Physicians Research Network (PRN) web was developed for more efficient trial protocol distribution and eligibility inquiries. The Medical University of South Carolina's Hollings Cancer Center trials program and two community oncology practices served as a testbed. In 581 man-hours over 18 months, 147 protocols were loaded into PRN. The trials program eliminated all protocol hardcopies except the masters, reduced photocopier use 59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage PRN. There were no known security breaches, downtime, or content-related problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method for distributing protocols and reducing distribution errors and delays because only a single copy of each protocol is maintained. Furthermore, PRN is being extended to serve other aspects of trial operations. PMID:8988471

Improvements in Clinical Trials Information Will Improve the Reproductive Health and Fertility of Cancer Patients.

PubMed

Dauti, Angela; Gerstl, Brigitte; Chong, Serena; Chisholm, Orin; Anazodo, Antoinette

2017-06-01

There are a number of barriers that result in cancer patients not being referred for oncofertility care, which include knowledge about reproductive risks of antineoplastic agents. Without this information, clinicians do not always make recommendations for oncofertility care. The objective of this study was to describe the level of reproductive information and recommendations that clinicians have available in clinical trial protocols regarding oncofertility management and follow-up, and the information that patients may receive in clinical trials patient information sheets or consent forms. A literature review of the 71 antineoplastic drugs included in the 68 clinical trial protocols showed that 68% of the antineoplastic drugs had gonadotoxic animal data, 32% had gonadotoxic human data, 83% had teratogenic animal data, and 32% had teratogenic human data. When the clinical trial protocols were reviewed, only 22% of the protocols reported the teratogenic risks and 32% of the protocols reported the gonadotoxic risk. Only 56% of phase 3 protocols had gonadotoxic information and 13% of phase 3 protocols had teratogenic information. Nine percent of the protocols provided fertility preservation recommendations and 4% provided reproductive information in the follow-up and survivorship period. Twenty-six percent had a section in the clinical trials protocol, which identified oncofertility information easily. When gonadotoxic and teratogenic effects of treatment were known, they were not consistently included in the clinical trial protocols and the lack of data for new drugs was not reported. Very few protocols gave recommendations for oncofertility management and follow-up following the completion of cancer treatment. The research team proposes a number of recommendations that should be required for clinicians and pharmaceutical companies developing new trials.

A systematic review and meta-analysis of self-help therapeutic interventions for obsessive-compulsive disorder: Is therapeutic contact key to overall improvement?

PubMed

Pearcy, Caitlin P; Anderson, Rebecca A; Egan, Sarah J; Rees, Clare S

2016-06-01

The presence of obsessive-compulsive disorder (OCD) can result in low quality of life, with significant impairments in social and occupational functioning. An increase in the dissemination of self-help programs has been observed in the treatment of OCD, and has provided improved accessibility to treatment. The present study examined the efficacy of self-help interventions for OCD in the context of therapeutic contact. Randomised controlled trials and quasi-experimental studies were identified through computerised database searches. Self-help format (bibliotherapy, internet-based, computerised), and therapeutic contact were examined for their effect on treatment outcomes. Eighteen studies targeting self-help for OCD met inclusion criteria with 1570 participants. The average post-treatment effect size (Hedges' g) of self-help interventions on primary outcomes was .51 (95% CI: .41 to 0.61). Subgroup analysis revealed large effect sizes for minimal-contact self-help (g = 0.91, 95% CI: 0.66 to 1.17), moderate effect sizes for predominantly self-help (g = 0.68, 95% CI: 0.40 to 0.96), and small effect sizes for self-administered self-help (g = 0.33, 95% CI: .18 to 0.47). A large variation of treatment approaches, amount of therapeutic contact, and risk of bias within each study may account for the large magnitude in effect sizes across studies. Additionally, the long-term follow-up effects of treatment approaches were not examined. A growing body of literature supporting to the use of self-help treatments for OCD is evident, however, further investigation through use of randomised controlled trials is required, particularly the use of stepped care and long-term effectiveness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nursing record systems: effects on nursing practice and health care outcomes.

PubMed

Currell, R; Urquhart, C

2003-01-01

A nursing record system is the record of care planned and/or given to individual patients/clients by qualified nurses or other caregivers under the direction of a qualified nurse. Nursing record systems may be an effective way of influencing nurse practice. To assess the effects of nursing record systems on nursing practice and patient outcomes. We searched The Cochrane Library, the EPOC trial register (October 2002), MEDLINE, Cinahl, Sigle, and databases of the Royal College of Nursing, King's Fund, the NHS Centre for Reviews and Dissemination, and the Institute of Electrical Engineers up to August 1999; and OCLC First Search, Department of Health database, NHS Register of Computer Applications and the Health Visitors' Association database up to the end of 1995. We hand searched the Journal of Nursing Administration (1971-1999), Computers in Nursing (1984-1999), Information Technology in Nursing (1989-1999) and reference lists of articles. We also hand searched the major health informatics conference proceedings. We contacted experts in the field of nursing informatics, suppliers of nursing computer systems, and relevant Internet groups. To update the review the Medline, Cinahl, British Nursing Index, Aslib Index to Theses databases were all searched from 1998 to 2002. The Journal of Nursing Administration, Computers in Nursing, Information Technology in Nursing were all hand searched up to 2002. The searches of the other databases and grey literature included in the original review, were not updated (except for Health Care Computing Conference and Med Info) as the original searches produced little relevant material. Randomised trials, controlled before and after studies and interrupted time series comparing one kind of nursing record system with another, in hospital, community or primary care settings. The participants were qualified nurses, students or health care assistants working under the direction of a qualified nurse and patients receiving care recorded and/or planned using nursing record systems. Two reviewers independently assessed trial quality and extracted data. Eight trials involving 1497 people were included. In three studies of client held records, there were no overall positive or negative effects, although some administrative benefits through fewer missing notes were suggested. A paediatric pain management sheet study showed a positive effect on the children's pain intensity. A computerised nursing care planning study showed a negative effect on documented nursing care planning, although two other computerised nursing information studies showed an increase in recording but no change in patient outcomes. Care planning took longer with these computerised systems, but the numbers of patients and nurses included in these studies was small. A controlled before-and-after study of two paper nursing record systems showed improvement in meeting documentation standards. No evidence was found of effects on practice attributable to changes in record systems. Although there is a paucity of studies of sufficient methodological rigour to yield reliable results in this area, it is clear from the literature that it is possible to set up randomised trials or other quasi-experimental designs needed to produce evidence for practice. The research undertaken so far may have suffered both from methodological problems and faulty hypotheses. Qualitative nursing research to explore the relationship between practice and information use, could be used as a precursor to the design and testing of nursing information systems.

Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis.

PubMed

Ali, Ather; Kahn, Janet; Rosenberger, Lisa; Perlman, Adam I

2012-10-04

Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists' clinical judgment and maintaining consistency with a prior pilot study. The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Clinicaltrials.gov NCT00970008 (18 August 2009).

Comparison of inter-trial recovery times for the determination of critical power and W' in cycling.

PubMed

Karsten, Bettina; Hopker, James; Jobson, Simon A; Baker, Jonathan; Petrigna, Luca; Klose, Andreas; Beedie, Christopher

2017-07-01

Critical Power (CP) and W' are often determined using multi-day testing protocols. To investigate this cumbersome testing method, the purpose of this study was to compare the differences between the conventional use of a 24-h inter-trial recovery time with those of 3 h and 30 min for the determination of CP and W'. 9 moderately trained cyclists performed an incremental test to exhaustion to establish the power output associated with the maximum oxygen uptake (p[Formula: see text] max ), and 3 protocols requiring time-to-exhaustion trials at a constant work-rate performed at 80%, 100% and 105% of p[Formula: see text] max. Design: Protocol A utilised 24-h inter-trial recovery (CP 24 /W' 24 ), protocol B utilised 3-h inter-trial recovery (CP 3 /W' 3 ), and protocol C used 30-min inter-trial recovery period (CP 0.5 /W' 0.5 ). CP and W' were calculated using the inverse time (1/t) versus power (P) relation (P = W'(1/t) + CP). 95% Limits of Agreement between protocol A and B were -9 to 15 W; -7.4 to 7.8 kJ (CP/W') and between protocol A and protocol C they were -27 to 22 W; -7.2 to 15.1 kJ (CP/W'). Compared to criterion protocol A, the average prediction error of protocol B was 2.5% (CP) and 25.6% (W'), whilst for protocol C it was 3.7% (CP) and 32.9% (W'). 3-h and 30-min inter-trial recovery time protocols provide valid methods of determining CP but not W' in cycling.

Applying Adaptive Variables in Computerised Adaptive Testing

ERIC Educational Resources Information Center

Triantafillou, Evangelos; Georgiadou, Elissavet; Economides, Anastasios A.

2007-01-01

Current research in computerised adaptive testing (CAT) focuses on applications, in small and large scale, that address self assessment, training, employment, teacher professional development for schools, industry, military, assessment of non-cognitive skills, etc. Dynamic item generation tools and automated scoring of complex, constructed…

Treatment algorithms and protocolized care.

PubMed

Morris, Alan H

2003-06-01

Excess information in complex ICU environments exceeds human decision-making limits and likely contributes to unnecessary variation in clinical care, increasing the likelihood of clinical errors. I reviewed recent critical care clinical trials searching for information about the impact of protocol use on clinically pertinent outcomes. Several recently published clinical trials illustrate the importance of distinguishing efficacy and effectiveness trials. One of these trials illustrates the danger of conducting effectiveness trials before the efficacy of an intervention is established. The trials also illustrate the importance of distinguishing guidelines and inadequately explicit protocols from adequately explicit protocols. Only adequately explicit protocols contain enough detail to lead different clinicians to the same decision when faced with the same clinical scenario. Differences between guidelines and protocols are important. Guidelines lack detail and provide general guidance that requires clinicians to fill in many gaps. Computerized or paper-based protocols are detailed and, when used for complex clinical ICU problems, can generate patient-specific, evidence-based therapy instructions that can be carried out by different clinicians with almost no interclinician variability. Individualization of patient therapy can be preserved by these protocols when they are driven by individual patient data. Explicit decision-support tools (eg, guidelines and protocols) have favorable effects on clinician and patient outcomes and can reduce the variation in clinical practice. Guidelines and protocols that aid ICU decision makers should be more widely distributed.

Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review.

PubMed

van Lent, Marlies; Rongen, Gerard A; Out, Henk J

2014-12-10

Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials. Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature. Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95). RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process.

Advancing beyond the system: telemedicine nurses' clinical reasoning using a computerised decision support system for patients with COPD - an ethnographic study.

PubMed

Barken, Tina Lien; Thygesen, Elin; Söderhamn, Ulrika

2017-12-28

Telemedicine is changing traditional nursing care, and entails nurses performing advanced and complex care within a new clinical environment, and monitoring patients at a distance. Telemedicine practice requires complex disease management, advocating that the nurses' reasoning and decision-making processes are supported. Computerised decision support systems are being used increasingly to assist reasoning and decision-making in different situations. However, little research has focused on the clinical reasoning of nurses using a computerised decision support system in a telemedicine setting. Therefore, the objective of the study is to explore the process of telemedicine nurses' clinical reasoning when using a computerised decision support system for the management of patients with chronic obstructive pulmonary disease. The factors influencing the reasoning and decision-making processes were investigated. In this ethnographic study, a combination of data collection methods, including participatory observations, the think-aloud technique, and a focus group interview was employed. Collected data were analysed using qualitative content analysis. When telemedicine nurses used a computerised decision support system for the management of patients with complex, unstable chronic obstructive pulmonary disease, two categories emerged: "the process of telemedicine nurses' reasoning to assess health change" and "the influence of the telemedicine setting on nurses' reasoning and decision-making processes". An overall theme, termed "advancing beyond the system", represented the connection between the reasoning processes and the telemedicine work and setting, where being familiar with the patient functioned as a foundation for the nurses' clinical reasoning process. In the telemedicine setting, when supported by a computerised decision support system, nurses' reasoning was enabled by the continuous flow of digital clinical data, regular video-mediated contact and shared decision-making with the patient. These factors fostered an in-depth knowledge of the patients and acted as a foundation for the nurses' reasoning process. Nurses' reasoning frequently advanced beyond the computerised decision support system recommendations. Future studies are warranted to develop more accurate algorithms, increase system maturity, and improve the integration of the digital clinical information with clinical experiences, to support telemedicine nurses' reasoning process.

Development and testing of a computerised 24-h recall questionnaire measuring fruit and snack consumption among 9-11 year olds.

PubMed

Moore, L; Tapper, K; Dennehy, A; Cooper, A

2005-07-01

To evaluate the validity, reliability and sensitivity of a computerised single day 24-h recall questionnaire designed for the comparison of children's fruit and snack consumption at the group (school) level. Relative validity and reliability were assessed in relation to (i) intake at school and (ii) intake throughout the whole day, using diary-assisted 24-h recall interviews and a 7-day test-retest procedure. Sensitivity was assessed in relation to intake by comparing results from schools with differing food policies, and by sex. Eight schools took part in the validity and reliability assessments, with 78 children completing the 24-h recall interviews and 195 children completing the test-retest procedure. A total of 43 schools (1890 children) took part in the sensitivity analysis. All children were aged 9-11 y. All schools were in South Wales and South-west England. For fruit intake at school, the questionnaire showed fair levels of validity at the individual level (kappa = 0.29). At the group level, there were little or no differences in fruit intake at school between the two measures and two occasions. The questionnaire was sufficiently sensitive to identify statistically significant differences between girls and boys, and between schools with different food policies. For snack intake at school, validity at the individual level was slightly lower (kappa = 0.220.25), but the data remained of value in analyses at the group level. For fruit and snack intake throughout the whole day there was little agreement at the individual level (kappa = 0.00-0.06), and at the group level there tended to be substantial differences between the two measures and two occasions. The computerised questionnaire is a quick and cost-effective means of assessing children's consumption of fruit at school. While further development is required to improve validity and reliability, it has the potential to be particularly useful in randomised controlled trials of school-based dietary interventions.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

PubMed

Kasenda, Benjamin; von Elm, Erik; You, John J; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Ebrahim, Shanil; Schandelmaier, Stefan; Sun, Xin; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2016-06-01

Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.

[Constraints on publication rights in industry-initiated clinical trials--secondary publication].

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2006-06-19

In 22 of 44 industry-initiated clinical trial protocols from 1994-95, it was noted that the sponsor either owned the data or needed to approve the manuscript; another 18 protocols had other constraints. Furthermore, in 16 trials, the sponsor had access to accumulating data, and in an additional 16 trials the sponsor could stop the trial at any time, for any reason. These facts were not noted in any of the trial reports. We found similar constraints on publication rights in 44 protocols from 2004. This tight sponsor control over industry-initiated trials should be changed.

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

PubMed

van den Bogert, Cornelis A; Souverein, Patrick C; Brekelmans, Cecile T M; Janssen, Susan W J; Koëter, Gerard H; Leufkens, Hubert G M; Bouter, Lex M

2017-08-01

The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating the Process of Generating a Clinical Trial Protocol

PubMed Central

Franciosi, Lui G.; Butterfield, Noam N.; MacLeod, Bernard A.

2002-01-01

The research protocol is the principal document in the conduct of a clinical trial. Its generation requires knowledge about the research problem, the potential experimental confounders, and the relevant Good Clinical Practices for conducting the trial. However, such information is not always available to authors during the writing process. A checklist of over 80 items has been developed to better understand the considerations made by authors in generating a protocol. It is based on the most cited requirements for designing and implementing the randomised controlled trial. Items are categorised according to the trial's research question, experimental design, statistics, ethics, and standard operating procedures. This quality assessment tool evaluates the extent that a generated protocol deviates from the best-planned clinical trial.

Physiotherapy for patients with soft tissue shoulder disorders: a systematic review of randomised clinical trials.

PubMed Central

van der Heijden, G. J.; van der Windt, D. A.; de Winter, A. F.

1997-01-01

OBJECTIVE: To assess the effectiveness of physiotherapy for patients with soft tissue shoulder disorders. DESIGN: A systematic computerised literature search of Medline and Embase, supplemented with citation tracking, for relevant trials with random allocation published before 1996. SUBJECTS: Patients treated with physiotherapy for disorders of soft tissue of the shoulder. MAIN OUTCOME MEASURES: Success rates, mobility, pain, functional status. RESULTS: Six of the 20 assessed trials satisfied at least five of eight validity criteria. Assessment of methods was often hampered by insufficient information on various validity criteria, and trials were often flawed by lack of blinding, high proportions of withdrawals from treatment, and high proportions of missing values. Trial sizes were small: only six trials included intervention groups of more than 25 patients. Ultrasound therapy, evaluated in six trials, was not shown to be effective. Four other trials favoured physiotherapy (laser therapy or manipulation), but the validity of their methods was unsatisfactory. CONCLUSIONS: There is evidence that ultrasound therapy is ineffective in the treatment of soft tissue shoulder disorders. Due to small trial sizes and unsatisfactory methods, evidence for the effectiveness of other methods of physiotherapy is inconclusive. For all methods of treatment, trials were too heterogeneous with respect to included patients, index and reference treatments, and follow up to merit valid statistical pooling. Future studies should show whether physiotherapy is superior to treatment with drugs, steroid injections, or a wait and see policy. PMID:9233322

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol: a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults.

PubMed

Dias, Joseph; Brealey, Stephen; Choudhary, Surabhi; Cook, Liz; Costa, Matthew; Fairhurst, Caroline; Hewitt, Catherine; Hodgson, Stephen; Jefferson, Laura; Jeyapalan, Kanagaratnam; Keding, Ada; Leighton, Paul; Rangan, Amar; Richardson, Gerry; Rothery, Claire; Taub, Nicholas; Thompson, John; Torgerson, David

2016-06-04

A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013.

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

PubMed

Dekkers, Olaf M; Cevallos, Myriam; Bührer, Jonas; Poncet, Antoine; Ackermann Rau, Sabine; Perneger, Thomas V; Egger, Matthias

2015-05-01

To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries. Copyright © 2015 Elsevier Inc. All rights reserved.

Developing a guideline for clinical trial protocol content: Delphi consensus survey

PubMed Central

2012-01-01

Background Recent evidence has highlighted deficiencies in clinical trial protocols, having implications for many groups. Existing guidelines for randomized clinical trial (RCT) protocol content vary substantially and most do not describe systematic methodology for their development. As one of three prespecified steps for the systematic development of a guideline for trial protocol content, the objective of this study was to conduct a three-round Delphi consensus survey to develop and refine minimum content for RCT protocols. Methods Panellists were identified using a multistep iterative approach, met prespecified minimum criteria and represented key stakeholders who develop or use clinical trial protocols. They were asked to rate concepts for importance in a minimum set of items for RCT protocols. The main outcome measures were degree of importance (scale of 1 to 10; higher scores indicating higher importance) and level of consensus for items. Results were presented as medians, interquartile ranges, counts and percentages. Results Ninety-six expert panellists participated in the Delphi consensus survey including trial investigators, methodologists, research ethics board members, funders, industry, regulators and journal editors. Response rates were between 88 and 93% per round. Overall, panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and 12 of low importance (median less than or equal to 5) for minimum trial protocol content. General and item-specific comments and subgroup results provided valuable insight for further discussions. Conclusions This Delphi process achieved consensus from a large panel of experts from diverse stakeholder groups on essential content for RCT protocols. It also highlights areas of divergence. These results, complemented by other empirical research and consensus meetings, are helping guide the development of a guideline for protocol content. PMID:23006145

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

PubMed

Bøtker, Hans Erik; Kharbanda, Rajesh; Schmidt, Michael R; Bøttcher, Morten; Kaltoft, Anne K; Terkelsen, Christian J; Munk, Kim; Andersen, Niels H; Hansen, Troels M; Trautner, Sven; Lassen, Jens Flensted; Christiansen, Evald Høj; Krusell, Lars R; Kristensen, Steen D; Thuesen, Leif; Nielsen, Søren S; Rehling, Michael; Sørensen, Henrik Toft; Redington, Andrew N; Nielsen, Torsten T

2010-02-27

Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes. Fondation Leducq. Copyright 2010 Elsevier Ltd. All rights reserved.

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis

PubMed Central

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-01-01

Introduction Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Methods Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. Ethics and dissemination A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. Trial registration number NCT023528702; Pre-results. PMID:27072573

Effectiveness of two web-based cognitive bias modification interventions targeting approach and attentional bias in gambling problems: study protocol for a pilot randomised controlled trial.

PubMed

Boffo, Marilisa; Willemen, Ronny; Pronk, Thomas; Wiers, Reinout W; Dom, Geert

2017-10-03

Disordered gamblers have phenotypical and pathological similarities to those with substance use disorders (SUD), including exaggerated automatic cognitive processing of motivationally salient gambling cues in the environment (i.e., attentional and approach bias). Cognitive bias modification (CBM) is a family of computerised interventions that have proved effective in successfully re-training these automatic cognitive biases in SUD. CBM interventions can, in principle, be administered online, thus showing potential of being a low-cost, low-threshold addition to conventional treatments. This paper presents the design of a pilot randomised controlled trial exploring the effectiveness of two web-based CBM interventions targeting attentional and approach bias towards gambling cues in a sample of Dutch and Belgian problematic and pathological gamblers. Participants (N = 182) are community-recruited adults experiencing gambling problems, who have gambled at least twice in the past 6 months and are motivated to change their gambling behaviour. After a baseline assessment session, participants are randomly assigned to one of four experimental conditions (attentional or approach bias training, or the placebo version of the two trainings) and complete six sessions of training. At baseline and before each training session, participants receive automated personalised feedback on their gambling motives and reasons to quit or reduce gambling. The post-intervention, 1-month, and 3-month follow-up assessments will examine changes in gambling behaviour, with frequency and expenditure as primary outcomes, and depressive symptoms and gambling-related attentional and approach biases as secondary outcomes. Secondary analyses will explore possible moderators (interference control capacity and trait impulsivity) and mediators (change in cognitive bias) of training effects on the primary outcomes. This study is the first to explore the effectiveness of an online CBM intervention for gambling problems. The results of this study can be extremely valuable for developing e-health interventions for gambling problems and further understanding the role of motivational implicit cognitive processes underlying problematic gambling behaviour. Netherlands Trial Register, NTR5096 . Registered on 11 March 2015.

An Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective Randomized Control Trials

PubMed Central

Logan, Jennifer K; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

2018-01-01

Purpose Effective clinical trial enrollment can be difficult in a protocol designs that contain one treatment arm that is perceived as being more “aggressive” or “favorable.” There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to enrollment, particularly the influence of timing, in context of three prospective randomized oncology trials where one arm was considered more aggressive. Methods and materials From June 2011 to March 2015, patients who were enrolled on three prospective institutional protocols (an oligometastatic non-small cell lung cancer (NSCLC) trial, and two proton vs. intensity-modulated radiation therapy (IMRT) trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher’s exact test, Student’s t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results 309 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligomet protocol: 5 vs. 3 appointments (P<0.001), NSCLC protocol: 4 vs. 3 appointments (P = 0.0018), esophageal protocol: 3 vs. 2 appointments (P = 0.0086No other factors or patient characteristics significantly affected ESR. Conclusion Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success, and may help overcome accrual barriers without compromising trial design. PMID:28244413

Do Computerised Training Programmes Designed to Improve Working Memory Work?

ERIC Educational Resources Information Center

Apter, Brian J. B.

2012-01-01

A critical review of working memory training research during the last 10 years is provided. Particular attention is given to research that has attempted to investigate the efficacy of commercially marketed computerised training programmes such as "Cogmed" and "Jungle Memory". Claimed benefits are questioned on the basis that research methodologies…

Demography, Social Structure and Learning through Life

ERIC Educational Resources Information Center

van der Veen, Ruud

2010-01-01

The modernisation of the Western world during the last two centuries has been a mix of industrialisation/computerisation and urbanisation. Consequently, reports on the future of adult learning and adult education have been a mix on the one hand of the learning requirements that follow from industrialisation/computerisation and on the other hand,…

Computerised Accounting Software; A Curriculum That Enhances an Accounting Programme

ERIC Educational Resources Information Center

Machera, Robert P.; Machera, Precious C.

2017-01-01

There has been an outcry in commerce and industry about students who fail to perform in the accounting department due to lack of "practical accounting skills". It is from this background that the researchers were motivated to investigate the impact of a Computerised Accounting Software Curriculum that enhances an Accounting Programme. At…

Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

PubMed Central

Calvert, Melanie; Kyte, Derek; Duffy, Helen; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; Ives, Jonathan; Draper, Heather; Brundage, Michael; Blazeby, Jane; King, Madeleine

2014-01-01

Background Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. Methods and Findings We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. Conclusions PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care. PMID:25333995

Development and evaluation of a centralised computerised registry for ureteric stents: completing the audit cycle.

PubMed

Davis, N F; Murray, G; O'Connor, T; Browne, C; MacCraith, E; Galvin, D; Mulvin, D; Quinlan, D; Lennon, G

2017-11-01

A forgotten ureteric stent may result in severe renal impairment leading to nephrectomy. To compare the effectiveness of a centralised computerised registry for monitoring ureteric stent activity with a previously established theatre stent logbook system. This prospective audit was performed in two 9-monthly intervals. During the first interval, insertion/removal of a ureteric stent was documented in a specific theatre stent logbook. In the second interval, an electronic centralised computerised registry was developed to document insertion/removal of a ureteric stent onto an accessible hospital server. A computerised traffic-light system was also developed to identify patients with an indwelling stent for >3 months. The primary outcome variable was the number of prolonged indwelling ureteric stents in both groups. During the first time interval, 188 ureteric stents were inserted and 182 (96%) were removed or changed. Six (4%) patients underwent insertion of a ureteric stent for a prolonged period of time (>6 months). This subgroup required complex endourological intervention for stent removal due to encrustation. During the second time interval, 157 ureteric stents were inserted and all patients had their stent removed or changed within 6 months. No patients in this group were lost to follow-up. This study demonstrates that a centralised computerised ureteric stent registry is superior to a conventional logbook for monitoring ureteric stent activity. We propose the introduction a centralised nationalised ureteric stent registry for eliminating the potential for prolonged or forgotten ureteric stents.

Optimizing Equivalence-Based Instruction: Effects of Training Protocols on Equivalence Class Formation

ERIC Educational Resources Information Center

Fienup, Daniel M.; Wright, Nicole A.; Fields, Lanny

2015-01-01

Two experiments evaluated the effects of the simple-to-complex and simultaneous training protocols on the formation of academically relevant equivalence classes. The simple-to-complex protocol intersperses derived relations probes with training baseline relations. The simultaneous protocol conducts all training trials and test trials in separate…

Effectiveness of a freely available computerised cognitive behavioural therapy programme (MoodGYM) for depression: Meta-analysis.

PubMed

Twomey, Conal; O'Reilly, Gary

2017-03-01

To investigate the effectiveness of a freely available computerised cognitive behavioural therapy programme (MoodGYM) for depression (primary outcome), anxiety and general psychological distress in adults. We searched PsycINFO, CINAHL Plus, MEDLINE, EMBASE, Social Science Citation Index and references from identified papers. To assess MoodGYM's effectiveness, we conducted random effects meta-analysis of identified randomised controlled trials. Comparisons from 11 studies demonstrated MoodGYM's effectiveness for depression symptoms at post-intervention, with a small effect size ( g = 0.36, 95% confidence interval: 0.17-0.56; I 2  = 78%). Removing the lowest quality studies ( k = 3) had minimal impact; however, adjusting for publication bias reduced the effect size to a non-significant level ( g = 0.17, 95% confidence interval: -0.01 to 0.38). Comparisons from six studies demonstrated MoodGYM's effectiveness for anxiety symptoms at post-intervention, with a medium effect size ( g = 0.57, 95% confidence interval: 0.20-0.94; I 2  = 85%). Although comparisons from six studies did not yield significance for MoodGYM's effectiveness for general psychological distress symptoms, the small effect size approached significance ( g = 0.34, 95% confidence interval: -0.04 to 0.68; I 2  = 79%). Both the type of setting (clinical vs non-clinical) and MoodGYM-developer authorship in randomised controlled trials had no meaningful influence on results; however, the results were confounded by the type of control deployed, level of clinician guidance, international region of trial and adherence to MoodGYM. The confounding influence of several variables, and presence of publication bias, means that the results of this meta-analysis should be interpreted with caution. Tentative support is provided for MoodGYM's effectiveness for symptoms of depression and general psychological distress. The programme's medium effect on anxiety symptoms demonstrates its utility for people with this difficulty. MoodGYM benefits from its free accessibility over the Internet, but adherence rates can be problematic and at the extreme can fall below 10%. We conclude that MoodGYM is best placed as a population-level intervention that is likely to benefit a sizeable minority of its users.

Evaluation of three indices for biofilm accumulation on complete dentures.

PubMed

Paranhos, Helena de Freitas Oliveira; Lovato da Silva, Claudia Helena; de Souza, Raphael Freitas; Pontes, Karina Matthes de Freitas

2010-03-01

The objective of this study was to evaluate the accuracy and reproducibility of three complete denture biofilm indices (Prosthesis Hygiene Index; Jeganathan et al. Index; Budtz-Jørgensen Index) by means of a computerised comparison method. Clinical studies into denture hygiene have employed a large number of biofilm indices among their outcome variables. However, the knowledge about the validity of these indices is still scarce. Sixty-two complete denture wearers were selected. The internal surfaces of the upper complete dentures were stained (5% erythrosine) and photographed. The slides were projected on paper, and the biofilm indices were applied over the photos by means of a scoring method. For the computerised method, the areas (total and biofilm-covered) were measured by dedicated software (Image Tool). In addition, to compare the results of the computerised method and Prosthetic Hygiene Index, a new scoring scale (including four and five graded) was introduced. For the Jeganathan et al. and Budtz-Jørgensen indices, the original scales were used. Values for each index were compared with the computerised method by the Friedman test. Their reproducibility was measured by means of weighed kappa. Significance for both tests was set at 0.05. The indices tested provided similar mean measures but they tended to overestimate biofilm coverage when compared with the computerised method (p < 0.001). Agreement between the Prosthesis Hygiene Index and the computerised method was not significant, regardless of the scale used. Jeghanathan et al. Index showed weak agreement, and consistent results were found for Budtz-Jorgensen Index (kappa = 0.19 and 0.39 respectively). Assessment of accuracy for the biofilm indices showed instrument bias that was similar among the tested methods. Weak inter-instrument reproducibility was found for the indices, except for the Budtz-Jørgensen Index. This should be the method of choice for clinical studies when more sophisticated approaches are not possible.

Sustainable reduction of antibiotic-induced antimicrobial resistance (ARena) in German ambulatory care: study protocol of a cluster randomised trial.

PubMed

Kamradt, Martina; Kaufmann-Kolle, Petra; Andres, Edith; Brand, Tonia; Klingenberg, Anja; Glassen, Katharina; Poß-Doering, Regina; Uhlmann, Lorenz; Hees, Katharina; Weber, Dorothea; Gutscher, Andreas; Wambach, Veit; Szecsenyi, Joachim; Wensing, Michel

2018-02-05

Despite many initiatives to enhance the rational use of antibiotics, there remains substantial room for improvement. The overall aim of this study is to optimise the appropriate use of antibiotics in German ambulatory care in patients with acute non-complicated infections (respiratory tract infections, such as bronchitis, sinusitis, tonsillitis and otitis media), community-acquired pneumonia and non-complicated cystitis, in order to counter the advancing antimicrobial resistance development. A three-armed cluster randomised trial will be conducted in 14 practice networks in two German federal states (Bavaria and North Rhine-Westphalia) and an added cohort that reflects standard care. The trial is accompanied by a process evaluation. Each arm will receive a different set of implementation strategies. Arm A receives a standard set, comprising of e-learning on communication with patients and quality circles with data-based feedback for physicians, information campaigns for the public, patient information material and performance-based additional reimbursement. Arm B receives this standard set plus e-learning on communication with patients and quality circles with data-based feedback tailored for non-physician health professionals of the practice team and information material for tablet computers (culture sensitive). Arm C receives the standard set as well as a computerised decision support system and quality circles in local multidisciplinary groups. The study aims to recruit 193 practices which will provide data on 23,934 patients each year (47,867 patients in total). The outcome evaluation is based on claims data and refers to established indicators of the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). Primary and secondary outcomes relate to prescribing of antibiotics, which will be analysed in multivariate regression models. The process evaluation is based on interviews with surveys among physicians, non-physician health professionals of the practice team and stakeholders. A patient survey is conducted in one of the study arms. Interview data will be qualitatively analysed using thematic framework analysis. Survey data of physicians, non-physician health professionals of the practice team and patients will use descriptive and exploratory statistics for analysis. The ARena trial will examine the effectiveness of large scale implementation strategies and explore their delivery in routine practice. ISRCTN, ISRCTN58150046 . Registered 24 August 2017.

Protocol for the PINCER trial: a cluster randomised trial comparing the effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices.

PubMed

Avery, Anthony J; Rodgers, Sarah; Cantrill, Judith A; Armstrong, Sarah; Elliott, Rachel; Howard, Rachel; Kendrick, Denise; Morris, Caroline J; Murray, Scott A; Prescott, Robin J; Cresswell, Kathrin; Sheikh, Aziz

2009-05-01

Medication errors are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. RESEARCH SUBJECT GROUP: "At-risk" patients registered with computerised general practices in two geographical regions in England. Parallel group pragmatic cluster randomised trial. Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs; - with a computer-recorded diagnosis of asthma being prescribed beta-blockers; - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. SECONDARY OUTCOME MEASURES; These relate to a number of other examples of potentially hazardous prescribing and medicines management. An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. QUALITATIVE ANALYSIS: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: study protocol for a randomised controlled trial.

PubMed

Norton, Christine; Emmanuel, Anton; Stevens, Natasha; Scott, S Mark; Grossi, Ugo; Bannister, Sybil; Eldridge, Sandra; Mason, James M; Knowles, Charles H

2017-03-24

Constipation affects up to 20% of adults. Chronic constipation (CC) affects 1-2% of adults. Patient dissatisfaction is high; nearly 80% feel that laxative therapy is unsatisfactory and symptoms have significant impact on quality of life. There is uncertainty about the value of specialist investigations and whether equipment-intensive therapies using biofeedback confer additional benefit when compared with specialist conservative advice. A three-arm, parallel-group, multicentre randomised controlled trial. to determine whether standardised specialist-led habit training plus pelvic floor retraining using computerised biofeedback is more clinically effective than standardised specialist-led habit training alone; to determine whether outcomes are improved by stratification based on prior investigation of anorectal and colonic pathophysiology. Primary outcome measure is response to treatment, defined as a 0.4-point (10% of scale) or greater reduction in Patient Assessment of Constipation-Quality of Life (PAC-QOL) score 6 months after the end of treatment. Other outcomes up to 12 months include symptoms, quality of life, health economics, psychological health and qualitative experience. (1) habit training (HT) with computer-assisted direct visual biofeedback (HTBF) results in an average reduction in PAC-QOL score of 0.4 points at 6 months compared to HT alone in unselected adults with CC, (2) stratification to either HT or HTBF informed by pathophysiological investigation (INVEST) results in an average 0.4-point reduction in PAC-QOL score at 6 months compared with treatment not directed by investigations (No-INVEST). Inclusion: chronic constipation in adults (aged 18-70 years) defined by self-reported symptom duration of more than 6 months; failure of previous laxatives or prokinetics and diet and lifestyle modifications. Consenting participants (n = 394) will be randomised to one of three arms in an allocation ratio of 3:3:2: [1] habit training, [2] habit training and biofeedback or [3] investigation-led allocation to one of these arms. Analysis will be on an intention-to-treat basis. This trial has the potential to answer some of the major outstanding questions in the management of chronic constipation, including whether costly invasive tests are warranted and whether computer-assisted direct visual biofeedback confers additional benefit to well-managed specialist advice alone. International Standard Randomised Controlled Trial Number: ISRCTN11791740. Registered on 16 July 2015.

Action to Support Practices Implement Research Evidence (ASPIRE): protocol for a cluster-randomised evaluation of adaptable implementation packages targeting 'high impact' clinical practice recommendations in general practice.

PubMed

Willis, Thomas A; Hartley, Suzanne; Glidewell, Liz; Farrin, Amanda J; Lawton, Rebecca; McEachan, Rosemary R C; Ingleson, Emma; Heudtlass, Peter; Collinson, Michelle; Clamp, Susan; Hunter, Cheryl; Ward, Vicky; Hulme, Claire; Meads, David; Bregantini, Daniele; Carder, Paul; Foy, Robbie

2016-02-29

There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice. The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences. ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability. ISRCTN91989345.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials

PubMed Central

Kasenda, Benjamin; von Elm, Erik; You, John J.; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J.; Stegert, Mihaela; Olu, Kelechi K.; Tikkinen, Kari A. O.; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M.; Mertz, Dominik; Akl, Elie A.; Bassler, Dirk; Busse, Jason W.; Nordmann, Alain; Gloy, Viktoria; Ebrahim, Shanil; Schandelmaier, Stefan; Sun, Xin; Vandvik, Per O.; Johnston, Bradley C.; Walter, Martin A.; Burnand, Bernard; Hemkens, Lars G.; Bucher, Heiner C.; Guyatt, Gordon H.; Briel, Matthias

2016-01-01

Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner’s right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors’ independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol. PMID:27352244

Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

PubMed Central

Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2015-01-01

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

Computerised cognitive training in acquired brain injury: A systematic review of outcomes using the International Classification of Functioning (ICF).

PubMed

Sigmundsdottir, Linda; Longley, Wendy A; Tate, Robyn L

2016-10-01

Computerised cognitive training (CCT) is an increasingly popular intervention for people experiencing cognitive symptoms. This systematic review evaluated the evidence for CCT in adults with acquired brain injury (ABI), focusing on how outcome measures used reflect efficacy across components of the International Classification of Functioning, Disability and Health. Database searches were conducted of studies investigating CCT to treat cognitive symptoms in adult ABI. Scientific quality was rated using the PEDro-P and RoBiNT Scales. Ninety-six studies met the criteria. Most studies examined outcomes using measures of mental functions (93/96, 97%); fewer studies included measures of activities/participation (41/96, 43%) or body structures (8/96, 8%). Only 14 studies (15%) provided Level 1 evidence (randomised controlled trials with a PEDro-P score ≥ 6/10), with these studies suggesting strong evidence for CCT improving processing speed in multiple sclerosis (MS) and moderate evidence for improving memory in MS and brain tumour populations. There is a large body of research examining the efficacy of CCT, but relatively few Level 1 studies and evidence is largely limited to body function outcomes. The routine use of outcome measures of activities/participation would provide more meaningful evidence for the efficacy of CCT. The use of body structure outcome measures (e.g., neuroimaging) is a newly emerging area, with potential to increase understanding of mechanisms of action for CCT.

Effectiveness of a Computerised Working Memory Training in Adolescents with Mild to Borderline Intellectual Disabilities

ERIC Educational Resources Information Center

Van der Molen, M. J.; Van Luit, J. E. H.; Van der Molen, M. W.; Klugkist, I.; Jongmans, M. J.

2010-01-01

Background: The goal of this study is to evaluate the effectiveness of a computerised working memory (WM) training on memory, response inhibition, fluid intelligence, scholastic abilities and the recall of stories in adolescents with mild to borderline intellectual disabilities attending special education. Method: A total of 95 adolescents with…

Evaluation of Computerised Reading-Assistance Systems for Reading Japanese Texts--From a Linguistic Point of View

ERIC Educational Resources Information Center

Toyoda, Etsuko

2016-01-01

For second-language learners to effectively and efficiently gather information from online texts in their target language, a well-designed computerised system to assist their reading is essential. While many articles and websites which introduce electronic second-language learning tools exist, evaluation of their functions in relation to the…

An Investigation of Integrative and Independent Listening Test Tasks in a Computerised Academic English Test

ERIC Educational Resources Information Center

Wei, Wei; Zheng, Ying

2017-01-01

This research provided a comprehensive evaluation and validation of the listening section of a newly introduced computerised test, Pearson Test of English Academic (PTE Academic). PTE Academic contains 11 item types assessing academic listening skills either alone or in combination with other skills. First, task analysis helped identify skills…

Using a Computerised Graphics Package to Achieve a Technology-Oriented Classroom

ERIC Educational Resources Information Center

Aladejana, Francisca; Idowu, Lanre

2009-01-01

The present situation in Nigeria involves students of fine arts, a practical-oriented subject, being exposed to poor methods of teaching with consequent poor performances. This study examined the extent to which the use of a computerised graphics package could make the classroom technology-oriented and affect the performance of learners. This is…

A New Computerised Advanced Theory of Mind Measure for Children with Asperger Syndrome: The ATOMIC

ERIC Educational Resources Information Center

Beaumont, Renae B.; Sofronoff, Kate

2008-01-01

This study examined the ability of children with Asperger Syndrome (AS) to attribute mental states to characters in a new computerised, advanced theory of mind measure: The Animated Theory of Mind Inventory for Children (ATOMIC). Results showed that children with AS matched on IQ, verbal comprehension, age and gender performed equivalently on…

Student Evaluation in Higher Education: A Comparison between Computer Assisted Assessment and Traditional Evaluation

ERIC Educational Resources Information Center

Ghilay, Yaron; Ghilay, Ruth

2012-01-01

The study examined advantages and disadvantages of computerised assessment compared to traditional evaluation. It was based on two samples of college students (n=54) being examined in computerised tests instead of paper-based exams. Students were asked to answer a questionnaire focused on test effectiveness, experience, flexibility and integrity.…

Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension.

PubMed

Calvert, Melanie; Kyte, Derek; Mercieca-Bebber, Rebecca; Slade, Anita; Chan, An-Wen; King, Madeleine T; Hunn, Amanda; Bottomley, Andrew; Regnault, Antoine; Chan, An-Wen; Ells, Carolyn; O'Connor, Daniel; Revicki, Dennis; Patrick, Donald; Altman, Doug; Basch, Ethan; Velikova, Galina; Price, Gary; Draper, Heather; Blazeby, Jane; Scott, Jane; Coast, Joanna; Norquist, Josephine; Brown, Julia; Haywood, Kirstie; Johnson, Laura Lee; Campbell, Lisa; Frank, Lori; von Hildebrand, Maria; Brundage, Michael; Palmer, Michael; Kluetz, Paul; Stephens, Richard; Golub, Robert M; Mitchell, Sandra; Groves, Trish

2018-02-06

Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.

Redactions in protocols for drug trials: what industry sponsors concealed.

PubMed

Marquardsen, Mikkel; Ogden, Michelle; Gøtzsche, Peter C

2018-04-01

Objective To describe the redactions in contemporary protocols for industry-sponsored randomised drug trials with patient relevant outcomes and to evaluate whether there was a legitimate rationale for the redactions. Design Cohort study. Under the Freedom of Information Act, we requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. We received 17 consecutive protocols, which had been redacted before we got them, and nine protocols without redactions. In five additional cases, the companies refused to let the committees give us access, and in three other cases, documents were missing. Participants Not applicable. Setting Not applicable. Main outcome measure Amount and nature of redactions in 22 predefined key protocol variables. Results The redactions were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials: data analysis, handling of missing data, detection and analysis of adverse events, definition of the outcomes, interim analyses and premature termination of the study, sponsor's access to incoming data while the study is running, ownership to the data and investigators' publication rights. The parts of the text that were redacted differed widely, both between companies and within the same company. Conclusions We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

PubMed Central

Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

2014-01-01

Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects present for a specific study phase may have been masked by combining protocols into phase groupings. Presence of informative censoring, such as withdrawal of some protocols from development if they began showing signs of lost interest among investigators, complicates interpretation of Kaplan-Meier estimates. Because this study constitutes a retrospective examination over an extended period of time, it does not allow for the precise identification of relative factors impacting timing. Conclusions Delays not only increase the time and cost to complete clinical trials, but they also diminish their usefulness by failing to answer research questions in time. We believe that research analyzing the time spent traversing defined intervals across the clinical trial protocol development and implementation continuum can stimulate business process analyses and reengineering efforts that could lead to reductions in the time from clinical trial concept to results, thereby accelerating progress in clinical research. PMID:24980279

Cognitive bias modification for social anxiety in adults who stutter: a feasibility study of a randomised controlled trial

PubMed Central

Gascoine, Sally; Carroll, Amy; Humby, Kate; Kingston, Mary; Shepstone, Lee; Risebro, Helen; Mackintosh, Bundy; Thompson, Tammy Davidson; Hodgekins, Jo

2017-01-01

Objective To determine the feasibility and acceptability of a computerised treatment for social anxiety disorder for adults who stutter including identification of recruitment, retention and completion rates, large cost drivers and selection of most appropriate outcome measure(s) to inform the design of a future definitive trial. Design Two-group parallel design (treatment vs placebo), double-blinded feasibility study. Participants: 31 adults who stutter. Intervention Attention training via an online probe detection task in which the stimuli were images of faces displaying neutral and disgusted expressions. Main outcome measures Psychological measures: Structured Clinical Interview Global Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic evaluation: resource use questionnaire; EuroQol three-dimension questionnaire. Acceptability: Likert Scale questionnaire of experience of trial, acceptability of the intervention and randomisation procedure. Results Feasibility of recruitment strategy was demonstrated. Participant feedback indicated that the intervention and definitive trial, including randomisation, would be acceptable to adults who stutter. Of the 31 participants who were randomised, 25 provided data at all three data collection points. Conclusions The feasibility study informed components of the intervention. Modifications to the design are needed before a definitive trial can be undertaken. Trial registration number I SRCTN55065978; Post-results. PMID:29061602

Template protocol for clinical trials investigating vaccines--focus on safety elements.

PubMed

Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2013-11-12

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Defining standardized protocols for determining the efficacy of a postmilking teat disinfectant following experimental exposure of teats to mastitis pathogens.

PubMed

Schukken, Y H; Rauch, B J; Morelli, J

2013-04-01

The objective of this paper was to define standardized protocols for determining the efficacy of a postmilking teat disinfectant following experimental exposure of teats to both Staphylococcus aureus and Streptococcus agalactiae. The standardized protocols describe the selection of cows and herds and define the critical points in performing experimental exposure, performing bacterial culture, evaluating the culture results, and finally performing statistical analyses and reporting of the results. The protocols define both negative control and positive control trials. For negative control trials, the protocol states that an efficacy of reducing new intramammary infections (IMI) of at least 40% is required for a teat disinfectant to be considered effective. For positive control trials, noninferiority to a control disinfectant with a published efficacy of reducing new IMI of at least 70% is required. Sample sizes for both negative and positive control trials are calculated. Positive control trials are expected to require a large trial size. Statistical analysis methods are defined and, in the proposed methods, the rate of IMI may be analyzed using generalized linear mixed models. The efficacy of the test product can be evaluated while controlling for important covariates and confounders in the trial. Finally, standards for reporting are defined and reporting considerations are discussed. The use of the defined protocol is shown through presentation of the results of a recent trial of a test product against a negative control. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Investigation of the Study Characteristics Affecting Clinical Trial Quality Using the Protocol Deviations Leading to Exclusion of Subjects From the Per Protocol Set Data in Studies for New Drug Application: A Retrospective Analysis.

PubMed

Kohara, Norihito; Kaneko, Masayuki; Narukawa, Mamoru

2018-01-01

The concept of the risk-based approach has been introduced as an effort to secure the quality of clinical trials. In the risk-based approach, identification and evaluation of risk in advance are considered important. For recently completed clinical trials, we investigated the relationship between study characteristics and protocol deviations leading to the exclusion of subjects from Per Protocol Set (PPS) efficacy analysis. New drugs approved in Japan in the fiscal year 2014-2015 were targeted in the research. The reasons for excluding subjects from the PPS efficacy analysis were described in 102 trials out of 492 in the summary of new drug application documents, which was publicly disclosed after the drug's regulatory approval. The author extracted these reasons along with the numbers of the cases and the study characteristics of each clinical trial. Then, the direct comparison, univariate regression analysis, and multivariate regression analysis was carried out based on the exclusion rate. The study characteristics for which exclusion of subjects from the PPS efficacy analysis were frequently observed was multiregional clinical trials in study region; inhalant and external use in administration route; Anti-infective for systemic use; Respiratory system, Dermatologicals, and Nervous system in therapeutic drug under the Anatomical Therapeutic Chemical Classification. In the multivariate regression analysis, the clinical trial variables of inhalant, Respiratory system, or Dermatologicals were selected as study characteristics leading to a higher exclusion rate. The characteristics of the clinical trial that is likely to cause protocol deviations that will affect efficacy analysis were suggested. These studies should be considered for specific attention and priority observation in the trial protocol or its monitoring plan and execution, such as a clear description of inclusion/exclusion criteria in the protocol, development of training materials to site staff, and/or trial subjects as specific risk-alleviating measures.

Future of computerised electrocardiography.

PubMed Central

Meijler, F L; Robles de Medina, E O; Helder, J C

1980-01-01

The advent of computerised electrocardiography has been of prime importance for the storage and retrieval of data, but none of the available systems is of universal application for analysis of patterns. Future needs require hierarchical systems of increasing degrees of complexity, depending on the source of requests, and there should be appropriate provision for review by cardiologists before the final report is issued. PMID:7000098

Review and Reward within the Computerised Peer-Assessment of Essays

ERIC Educational Resources Information Center

Davies, Phil

2009-01-01

This article details the implementation and use of a "Review Stage" within the CAP (computerised assessment by peers) tool as part of the assessment process for a post-graduate module in e-learning. It reports upon the effect of providing the students with a "second chance" in marking and commenting their peers' essays having been able to view the…

Planning and reporting of quality-of-life outcomes in cancer trials

PubMed Central

Schandelmaier, S.; Conen, K.; von Elm, E.; You, J. J.; Blümle, A.; Tomonaga, Y.; Amstutz, A.; Briel, M.; Kasenda, B.

2015-01-01

Background Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. Design Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. Results Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. Conclusions About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers. PMID:26133966

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials inmore » NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.« less

The effects of sweep numbers per average and protocol type on the accuracy of the p300-based concealed information test.

PubMed

Dietrich, Ariana B; Hu, Xiaoqing; Rosenfeld, J Peter

2014-03-01

In the first of two experiments, we compared the accuracy of the P300 concealed information test protocol as a function of numbers of trials experienced by subjects and ERP averages analyzed by investigators. Contrary to Farwell et al. (Cogn Neurodyn 6(2):115-154, 2012), we found no evidence that 100 trial based averages are more accurate than 66 or 33 trial based averages (all numbers led to accuracies of 84-94 %). There was actually a trend favoring the lowest trial numbers. The second study compared numbers of irrelevant stimuli recalled and recognized in the 3-stimulus protocol versus the complex trial protocol (Rosenfeld in Memory detection: theory and application of the concealed information test, Cambridge University Press, New York, pp 63-89, 2011). Again, in contrast to expectations from Farwell et al. (Cogn Neurodyn 6(2):115-154, 2012), there were no differences between protocols, although there were more irrelevant stimuli recognized than recalled, and irrelevant 4-digit number group stimuli were neither recalled nor recognized as well as irrelevant city name stimuli. We therefore conclude that stimulus processing in the P300-based complex trial protocol-with no more than 33 sweep averages-is adequate to allow accurate detection of concealed information.

A privacy preserving protocol for tracking participants in phase I clinical trials.

PubMed

El Emam, Khaled; Farah, Hanna; Samet, Saeed; Essex, Aleksander; Jonker, Elizabeth; Kantarcioglu, Murat; Earle, Craig C

2015-10-01

Some phase 1 clinical trials offer strong financial incentives for healthy individuals to participate in their studies. There is evidence that some individuals enroll in multiple trials concurrently. This creates safety risks and introduces data quality problems into the trials. Our objective was to construct a privacy preserving protocol to track phase 1 participants to detect concurrent enrollment. A protocol using secure probabilistic querying against a database of trial participants that allows for screening during telephone interviews and on-site enrollment was developed. The match variables consisted of demographic information. The accuracy (sensitivity, precision, and negative predictive value) of the matching and its computational performance in seconds were measured under simulated environments. Accuracy was also compared to non-secure matching methods. The protocol performance scales linearly with the database size. At the largest database size of 20,000 participants, a query takes under 20s on a 64 cores machine. Sensitivity, precision, and negative predictive value of the queries were consistently at or above 0.9, and were very similar to non-secure versions of the protocol. The protocol provides a reasonable solution to the concurrent enrollment problems in phase 1 clinical trials, and is able to ensure that personal information about participants is kept secure. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Computerised lung sound analysis to improve the specificity of paediatric pneumonia diagnosis in resource-poor settings: protocol and methods for an observational study

PubMed Central

Gilman, Robert H; Tielsch, James M; Steinhoff, Mark; Figueroa, Dante; Rodriguez, Shalim; Caffo, Brian; Tracey, Brian; Elhilali, Mounya; West, James; Checkley, William

2012-01-01

Introduction WHO case management algorithm for paediatric pneumonia relies solely on symptoms of shortness of breath or cough and tachypnoea for treatment and has poor diagnostic specificity, tends to increase antibiotic resistance. Alternatives, including oxygen saturation measurement, chest ultrasound and chest auscultation, exist but with potential disadvantages. Electronic auscultation has potential for improved detection of paediatric pneumonia but has yet to be standardised. The authors aim to investigate the use of electronic auscultation to improve the specificity of the current WHO algorithm in developing countries. Methods This study is designed to test the hypothesis that pulmonary pathology can be differentiated from normal using computerised lung sound analysis (CLSA). The authors will record lung sounds from 600 children aged ≤5 years, 100 each with consolidative pneumonia, diffuse interstitial pneumonia, asthma, bronchiolitis, upper respiratory infections and normal lungs at a children's hospital in Lima, Peru. The authors will compare CLSA with the WHO algorithm and other detection approaches, including physical exam findings, chest ultrasound and microbiologic testing to construct an improved algorithm for pneumonia diagnosis. Discussion This study will develop standardised methods for electronic auscultation and chest ultrasound and compare their utility for detection of pneumonia to standard approaches. Utilising signal processing techniques, the authors aim to characterise lung sounds and through machine learning, develop a classification system to distinguish pathologic sounds. Data will allow a better understanding of the benefits and limitations of novel diagnostic techniques in paediatric pneumonia. PMID:22307098

Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial.

PubMed

Mir, Fatima; Quadri, Farheen; Mach, Ondrej; Ahmed, Imran; Bhatti, Zaid; Khan, Asia; Rehman, Najeeb Ur; Durry, Elias; Salama, Maha; Oberste, Steven M; Weldon, William C; Sutter, Roland W; Zaidi, Anita K M

2015-08-01

Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72·4-86·1) with mOPV1-1 week, 108/135 (80%, 73·2-86·8) with mOPV1-2 weeks, 129/148 (87%, 80·9-92·0) with mOPV1-4 weeks, and 107/136 (79%, 71·8-85·6) with bOPV-4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis. We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict--eg, during cease-fire periods. In such situations, we recommend shortening the interval between OPV doses to 7 days. World Health Organization. Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

Site visits to initiate recruitment in a clinical trial: does it matter who conducts the visit? Protocol for implementation in trials.

PubMed

Nollett, Claire; Kelson, Mark; Hood, Kerenza

2016-11-01

The Study Within a Trial (SWAT) program exists to 'embed research within research, so as to resolve uncertainties about the different ways of designing, conducting, analyzing, and interpreting evaluations of health and social care' (1). Published in this journal in 2013, a template for the first SWAT protocol outlined an investigation into the effects of site visits by the principal investigator on recruitment in multicentre randomized controlled trials (1). We have now designed a SWAT protocol to extend this question and ask 'does it matter who conducts the site visit?' Our aim is to provide a protocol that trials can implement to address this research question. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Decision tools in health care: focus on the problem, not the solution.

PubMed

Liu, Joseph; Wyatt, Jeremy C; Altman, Douglas G

2006-01-20

Systematic reviews or randomised-controlled trials usually help to establish the effectiveness of drugs and other health technologies, but are rarely sufficient by themselves to ensure actual clinical use of the technology. The process from innovation to routine clinical use is complex. Numerous computerised decision support systems (DSS) have been developed, but many fail to be taken up into actual use. Some developers construct technologically advanced systems with little relevance to the real world. Others did not determine whether a clinical need exists. With NHS investing 5 billion pounds sterling in computer systems, also occurring in other countries, there is an urgent need to shift from a technology-driven approach to one that identifies and employs the most cost-effective method to manage knowledge, regardless of the technology. The generic term, 'decision tool' (DT), is therefore suggested to demonstrate that these aids, which seem different technically, are conceptually the same from a clinical viewpoint. Many computerised DSSs failed for various reasons, for example, they were not based on best available knowledge; there was insufficient emphasis on their need for high quality clinical data; their development was technology-led; or evaluation methods were misapplied. We argue that DSSs and other computer-based, paper-based and even mechanical decision aids are members of a wider family of decision tools. A DT is an active knowledge resource that uses patient data to generate case specific advice, which supports decision making about individual patients by health professionals, the patients themselves or others concerned about them. The identification of DTs as a consistent and important category of health technology should encourage the sharing of lessons between DT developers and users and reduce the frequency of decision tool projects focusing only on technology. The focus of evaluation should become more clinical, with the impact of computer-based DTs being evaluated against other computer, paper- or mechanical tools, to identify the most cost effective tool for each clinical problem. We suggested the generic term 'decision tool' to demonstrate that decision-making aids, such as computerised DSSs, paper algorithms, and reminders are conceptually the same, so the methods to evaluate them should be the same.

Demonstrating the effectiveness of body armour: a pilot prospective computerised surface wound mapping trial performed at the Role 3 hospital in Afghanistan.

PubMed

Breeze, Johno; Allanson-Bailey, L S; Hepper, A E; Midwinter, M J

2015-03-01

Modern body armour clearly reduces injury incidence and severity, but evidence to actually objectively demonstrate this effect is scarce. Although the Joint Theatre Trauma Registry (JTTR) alone cannot relate injury pattern to body armour coverage, the addition of computerised Surface Wound Mapping (SWM) may enable this utility. Surface wound locations of all UK and NATO coalition soldiers, Afghan National Army and Police and local nationals injured by explosively propelled fragments and treated in the Role 3 UK-led Field Hospital in Camp Bastion, Afghanistan, between 8 July and 20 October 2012 were prospectively recorded. The Abbreviated Injury Scores (AIS) and relative risk of casualties sustaining injuries under a type of body armour were compared with those that did not wear that armour. Casualties wearing a combat helmet were 2.7 times less likely to sustain a fragmentation wound to the head than those that were unprotected (mean AIS of 2.9 compared with 4.1). Casualties wearing a body armour vest were 4.1 times less likely to sustain a fragmentation wound to the chest or abdomen than those that were unprotected (mean AIS of 2.9 compared with 3.9). Casualties wearing pelvic protection were 10 times less likely to sustain a fragmentation wound to the pelvis compared with those that were unprotected (mean AIS of 3.4 compared with 3.9). Computerised SWM has objectively demonstrated the ability of body armour worn on current operations in Afghanistan to reduce wound incidence and severity. We recognise this technique is limited in that it only records the surface wound location and may be specific to this conflict. However, gathering electronic SWM at the same time as recording injuries for the JTTR was simple, required little extra time and therefore we would recommend its collection during future conflicts. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

ASCOT: a text mining-based web-service for efficient search and assisted creation of clinical trials

PubMed Central

2012-01-01

Clinical trials are mandatory protocols describing medical research on humans and among the most valuable sources of medical practice evidence. Searching for trials relevant to some query is laborious due to the immense number of existing protocols. Apart from search, writing new trials includes composing detailed eligibility criteria, which might be time-consuming, especially for new researchers. In this paper we present ASCOT, an efficient search application customised for clinical trials. ASCOT uses text mining and data mining methods to enrich clinical trials with metadata, that in turn serve as effective tools to narrow down search. In addition, ASCOT integrates a component for recommending eligibility criteria based on a set of selected protocols. PMID:22595088

ASCOT: a text mining-based web-service for efficient search and assisted creation of clinical trials.

PubMed

Korkontzelos, Ioannis; Mu, Tingting; Ananiadou, Sophia

2012-04-30

Clinical trials are mandatory protocols describing medical research on humans and among the most valuable sources of medical practice evidence. Searching for trials relevant to some query is laborious due to the immense number of existing protocols. Apart from search, writing new trials includes composing detailed eligibility criteria, which might be time-consuming, especially for new researchers. In this paper we present ASCOT, an efficient search application customised for clinical trials. ASCOT uses text mining and data mining methods to enrich clinical trials with metadata, that in turn serve as effective tools to narrow down search. In addition, ASCOT integrates a component for recommending eligibility criteria based on a set of selected protocols.

The effects of 2 weeks of interval vs continuous walking training on glycaemic control and whole-body oxidative stress in individuals with type 2 diabetes: a controlled, randomised, crossover trial.

PubMed

Karstoft, Kristian; Clark, Margaret A; Jakobsen, Ida; Müller, Ida A; Pedersen, Bente K; Solomon, Thomas P J; Ried-Larsen, Mathias

2017-03-01

The aim of this study was to evaluate the effects of oxygen consumption-matched short-term interval walking training (IWT) vs continuous walking training (CWT) on glycaemic control, including glycaemic variability, in individuals with type 2 diabetes. We also assessed whether any training-induced improvements in glycaemic control were associated with systemic oxidative stress levels. Participants (n = 14) with type 2 diabetes completed a crossover trial using three interventions (control intervention [CON], CWT and IWT), each lasting 2 weeks. These were performed in a randomised order (computerised generated randomisation) and separated by washout periods of 4 or 8 weeks after CON or training interventions, respectively. Training included ten supervised treadmill sessions, lasting 60 min/session, and was performed at the research facility. CWT was performed at moderate walking speed (75.6% ± 2.5% of walking peak oxygen consumption [[Formula: see text

Standardized patient walkthroughs in the National Drug Abuse Treatment Clinical Trials Network: common challenges to protocol implementation.

PubMed

Fussell, Holly E; Kunkel, Lynn E; McCarty, Dennis; Lewy, Colleen S

2011-09-01

Training research staff to implement clinical trials occurring in community-based addiction treatment programs presents unique challenges. Standardized patient walkthroughs of study procedures may enhance training and protocol implementation. Examine and discuss cross-site and cross-study challenges of participant screening and data collection procedures identified during standardized patient walkthroughs of multi-site clinical trials. Actors portrayed clients and "walked through" study procedures with protocol research staff. The study completed 57 walkthroughs during implementation of 4 clinical trials. Observers and walkthrough participants identified three areas of concern (consent procedures, screening and assessment processes, and protocol implementation) and made suggestions for resolving the concerns. Standardized patient walkthroughs capture issues with study procedures previously unidentified with didactic training or unscripted rehearsals. Clinical trials within the National Drug Abuse Treatment Clinical Trials Network are conducted in addiction treatment centers that vary on multiple dimensions. Based on walkthrough observations, the national protocol team and local site leadership modify standardized operating procedures and resolve cross-site problems prior to recruiting study participants. The standardized patient walkthrough improves consistency across study sites and reduces potential site variation in study outcomes.

Clinical Trials Management | Division of Cancer Prevention

Cancer.gov

Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded

A Computerized Wear Particle Atlas for Ferrogram and Filtergram Analyses

DTIC Science & Technology

1998-01-01

A Computerised Wear Particle Atlas for Ferrogram and Filtergram Analyses Jian G. Ding Lubrosoft P/L P 0 Box 2368, Rowville Melbourne VIC 3178...Australia (61-3) 9759-9083 Abstract: A new computerised wear particle atlas has been developed for identification of solid particles and...differentiation of wear severity of lubricated equipment. This atlas contains 892 images of representative solid particles selected from thousands of filtergram

A systematic review of computerised serious educational games about alcohol and other drugs for adolescents.

PubMed

Rodriguez, Daniel M; Teesson, Maree; Newton, Nicola C

2014-03-01

Serious educational games (SEG) have been shown to be effective in educating young people about a range of topics, including languages and maths. This paper identifies the use of computerised SEGs in education about alcohol and other drugs and reviews their impact on the prevention of alcohol and drug use. The Cochrane Library, EMBASE, MEDLINE, ERIC, Scopus, psychINFO, pubMED and DRUG databases were searched in February 2013. Additional publications were obtained from the reference lists of the relevant papers. Studies were included if they described an evaluation of a computerised SEG that targeted alcohol and/or other drugs and had been trialled with adolescents. Eight SEGs were identified targeting tobacco, alcohol, cannabis, methamphetamine, ecstasy, inhalants, cocaine and opioids. Six reported positive outcomes in terms of increased content knowledge and two reported increased negative attitudes towards the targeted drugs. Only one reported a decrease in the frequency of drug use. This is the first review of the efficacy of computerised SEGs for alcohol and other drugs for adolescents. Results suggest that SEGs can increase content knowledge of alcohol and other drugs. Evidence concerning impacts on negative attitudes and alcohol and drug use is limited, with few studies examining these outcomes. © 2013 Australasian Professional Society on Alcohol and other Drugs.

Optimization of protocol design: a path to efficient, lower cost clinical trial execution

PubMed Central

Malikova, Marina A

2016-01-01

Managing clinical trials requires strategic planning and efficient execution. In order to achieve a timely delivery of important clinical trials’ outcomes, it is useful to establish standardized trial management guidelines and develop robust scoring methodology for evaluation of study protocol complexity. This review will explore the challenges clinical teams face in developing protocols to ensure that the right patients are enrolled and the right data are collected to demonstrate that a drug is safe and efficacious, while managing study costs and study complexity based on proposed comprehensive scoring model. Key factors to consider when developing protocols and techniques to minimize complexity will be discussed. A methodology to identify processes at planning phase, approaches to increase fiscal return and mitigate fiscal compliance risk for clinical trials will be addressed. PMID:28031939

A computer decision aid for medical prevention: a pilot qualitative study of the Personalized Estimate of Risks (EsPeR) system

PubMed Central

Colombet, Isabelle; Dart, Thierry; Leneveut, Laurence; Zunino, Sylvain; Ménard, Joël; Chatellier, Gilles

2003-01-01

Background Many preventable diseases such as ischemic heart diseases and breast cancer prevail at a large scale in the general population. Computerized decision support systems are one of the solutions for improving the quality of prevention strategies. Methods The system called EsPeR (Personalised Estimate of Risks) combines calculation of several risks with computerisation of guidelines (cardiovascular prevention, screening for breast cancer, colorectal cancer, uterine cervix cancer, and prostate cancer, diagnosis of depression and suicide risk). We present a qualitative evaluation of its ergonomics, as well as it's understanding and acceptance by a group of general practitioners. We organised four focus groups each including 6–11 general practitioners. Physicians worked on several structured clinical scenari os with the help of EsPeR, and three senior investigators leaded structured discussion sessions. Results The initial sessions identified several ergonomic flaws of the system that were easily corrected. Both clinical scenarios and discussion sessions identified several problems related to the insufficient comprehension (expression of risks, definition of familial history of disease), and difficulty for the physicians to accept some of the recommendations. Conclusion Educational, socio-professional and organisational components (i.e. time constraints for training and use of the EsPeR system during consultation) as well as acceptance of evidence-based decision-making should be taken into account before launching computerised decision support systems, or their application in randomised trials. PMID:14641924

Recruitment of patients into head and neck clinical trials: acceptability of studies to patients from perspective of the research team.

PubMed

Ho, M W; Pick, A S; Sutton, D N; Dyker, K; Cardale, K; Gilbert, K; Johnson, J; Quantrill, J; McCaul, J A

2018-05-01

We reviewed longitudinal recruitment data to assess recruitment into head and neck cancer trials, and to identify factors that could influence this and affect their acceptability to patients. We retrieved data from the prospective computerised database (2009-2016) to measure acceptability to patients using the recruitment:screening ratio, and compared observational with interventional studies, single specialty (or site) with multispecialty (or site) studies, and "step-up" randomisation with "non-inferiority" randomisation designs. A total of 1283 patients were screened and 583 recruited. The recruitment:screening ratio for all National Institute for Health Research (NIHR) portfolio studies combined was 0.47 (486/1133). Studies that involved treatment by several specialties or at several sites had a significantly adverse impact on acceptability (p=0.01). Recruitment into non-inferiority randomised controlled studies was lower than that into step-up randomised studies (p=0.06). The complexity of a study's design did not compromise recruitment. Treatment across several specialties or several sites and perceived non-inferiority designs, reduced the acceptability of some trials. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

[A computerised clinical decision-support system for the management of depression in Primary Care].

PubMed

Aragonès, Enric; Comín, Eva; Cavero, Myriam; Pérez, Víctor; Molina, Cristina; Palao, Diego

Despite its clinical relevance and its importance as a public health problem, there are major gaps in the management of depression. Evidence-based clinical guidelines are useful to improve processes and clinical outcomes. In order to make their implementation easier these guidelines have been transformed into computerised clinical decision support systems. In this article, a description is presented on the basics and characteristics of a new computerised clinical guideline for the management of major depression, developed in the public health system in Catalonia. This tool helps the clinician to establish reliable and accurate diagnoses of depression, to choose the best treatment a priori according to the disease and the patient characteristics. It also emphasises the importance of systematic monitoring to assess the clinical course, and to adjust therapeutic interventions to the patient's needs at all times. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

The Melbourne East Monash General Practice Database (MAGNET): Using data from computerised medical records to create a platform for primary care and health services research.

PubMed

Mazza, Danielle; Pearce, Christopher; Turner, Lyle Robert; De Leon-Santiago, Maria; McLeod, Adam; Ferriggi, Jason; Shearer, Marianne

2016-07-04

The Melbourne East MonAsh GeNeral PracticE DaTabase (MAGNET) research platform was launched in 2013 to provide a unique data source for primary care and health services research in Australia.  MAGNET contains information from the computerised records of 50 participating general practices and includes data from the computerised medical records of more than 1,100,000 patients.  The data extracted is patient-level episodic information and includes a variety of fields related to patient demographics and historical clinical information, along with the characteristics of the participating general practices.  While there are limitations to the data that is currently available, the MAGNET research platform continues to investigate other avenues for improving the breadth and quality of data, with the aim of providing a more comprehensive picture of primary care in Australia.

Computerised electronic foetal heart rate monitoring in labour: automated contraction identification.

PubMed

Georgieva, A; Payne, S J; Redman, C W G

2009-12-01

The foetal heart rate (FHR) response to uterine contractions is crucial to detect foetal distress by electronic FHR monitoring during labour. We are developing a new automated system (OxSys) for decision support in labour, using the Oxford database of intrapartum FHR records. We describe here a novel technique for automated detection of uterus contractions. In addition, we present a comparison of the new method with four other computerised approaches. During training, OxSys achieved sensitivity above 95% and positive predictive value (PPV) of up to 90% for traces of good quality. During testing, OxSys achieved sensitivity = 87% and PPV = 75%. For comparison, a second clinical expert obtained sensitivity = 93% and PPV = 80%, and all other computerised approaches achieved lower values. It was concluded that the proposed method can be employed with confidence in our study on foetal health assessment in labour and future OxSys development.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

PubMed Central

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-01-01

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. PMID:26811365

Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.

PubMed

Grant, Aileen; Dreischulte, Tobias; Treweek, Shaun; Guthrie, Bruce

2012-08-28

Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.

Improving Conduct and Feasibility of Clinical Trials to Evaluate Antibacterial Drugs to Treat Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team.

PubMed

Knirsch, Charles; Alemayehu, Demissie; Botgros, Radu; Comic-Savic, Sabrina; Friedland, David; Holland, Thomas L; Merchant, Kunal; Noel, Gary J; Pelfrene, Eric; Reith, Christina; Santiago, Jonas; Tiernan, Rosemary; Tenearts, Pamela; Goldsack, Jennifer C; Fowler, Vance G

2016-08-15

The etiology of hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is often multidrug-resistant infections. The evaluation of new antibacterial drugs for efficacy in this population is important, as many antibacterial drugs have demonstrated limitations when studied in this population. HABP/VABP trials are expensive and challenging to conduct due to protocol complexity and low patient enrollment, among other factors. The Clinical Trials Transformation Initiative (CTTI) seeks to advance antibacterial drug development by streamlining HABP/VABP clinical trials to improve efficiency and feasibility while maintaining ethical rigor, patient safety, information value, and scientific validity. In 2013, CTTI engaged a multidisciplinary group of experts to discuss challenges impeding the conduct of HABP/VABP trials. Separate workstreams identified challenges associated with HABP/VABP protocol complexity. The Project Team developed potential solutions to streamline HABP/VABP trials using a Quality by Design approach. CTTI recommendations focus on 4 key areas to improve HABP/VABP trials: informed consent processes/practices, protocol design, choice of an institutional review board (IRB), and trial outcomes. Informed consent processes should include legally authorized representatives. Protocol design decisions should focus on eligibility criteria, prestudy antibacterial therapy considerations, use of new diagnostics, and sample size. CTTI recommends that sponsors use a central IRB and discuss trial endpoints with regulators, including defining a clinical failure and evaluating the impact of concomitant antibacterial drugs. Streamlining HABP/VABP trials by addressing key protocol elements can improve trial startup and patient recruitment/retention, reduce trial complexity and costs, and ensure patient safety while advancing antibacterial drug development. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Guidelines for randomized clinical trial protocol content: a systematic review

PubMed Central

2012-01-01

Background All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. Methods We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Results Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Conclusions Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed. PMID:23006870

Guidelines for randomized clinical trial protocol content: a systematic review.

PubMed

Tetzlaff, Jennifer M; Chan, An-Wen; Kitchen, Jessica; Sampson, Margaret; Tricco, Andrea C; Moher, David

2012-09-24

All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed.

Impairment of facial recognition in patients with right cerebral infarcts quantified by computer aided "morphing".

PubMed Central

Rösler, A; Lanquillon, S; Dippel, O; Braune, H J

1997-01-01

OBJECTIVE: To investigate where facial recognition is located anatomically and to establish whether there is a graded transition from unimpaired recognition of faces to complete prosopagnosia after infarctions in the territory of the middle cerebral artery. METHODS: A computerised morphing program was developed which shows 30 frames gradually changing from portrait photographs of unfamiliar persons to those of well known persons. With a standardised protocol, 31 patients with right and left sided infarctions in the territory of the middle cerebral artery and an age and sex matched control group were compared by non-parametric tests. RESULTS AND CONCLUSION: Facial recognition in patients with right sided lesions was significantly impaired compared with controls and with patients with left sided lesions. A graded impairment in facial recognition in patients with right sided ischaemic infarcts in the territory of the middle cerebral artery seems to exist. Images PMID:9069481

Implementing security in a distributed web-based EHCR.

PubMed

Sucurovic, Snezana

2007-01-01

In many countries there are initiatives for building an integrated patient-centric electronic health record. There are also initiatives for transnational integrations. These growing demands for integration result from the fact that it can provide improving healthcare treatments and reducing the cost of healthcare services. While in European highly developed countries computerisation in healthcare sector began in the 1970s and reached a high level, some developing countries, and Serbia among them, have started computerisation recently. This is why MEDIS (MEDical Information System) is aimed at integration itself from the very beginning instead of integration of heterogeneous information systems on a middle layer or using HL7 protocol. The implementation of a national healthcare information system requires using standards as integrated and widely accepted solutions. Therefore, we have started building MEDIS to meet the requirements of CEN ENV 13606 and CEN ENV 13729 standards. The prototype version has a distributed component-based architecture with modern security solutions applied. MEDIS has been implemented as a federated system where the central server hosts basic EHCR information about a patient, and clinical servers contain their own part of patients' EHCR. At present, there is an initial version of prototype planned to be deployed at first in a small community. In particular, open source API for X.509 authentication and authorisation has been developed. Our project meets the requirements for education in health informatics, including appropriate knowledge and skills on EHCR. The points included in this article have been presented on several national conferences and widely discussed. MEDIS has explored a federated, component-based EHCR architecture and related security aspects. In its initial version it shows acceptable performances and administrative simplicity. It emphasizes the importance of using standards in building EHCR in our country, in order to prepare it for future integrations.

Medical communication and technology: a video-based process study of the use of decision aids in primary care consultations.

PubMed

Kaner, Eileen; Heaven, Ben; Rapley, Tim; Murtagh, Madeleine; Graham, Ruth; Thomson, Richard; May, Carl

2007-01-10

Much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial. A video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour. Median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19-26) minutes to work through compared to 31 (16-41) minutes for the implicit tool; and 44 (39-55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58-66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversation Irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary care.

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

PubMed

Devereux, Graham; Cotton, Seonaidh; Barnes, Peter; Briggs, Andrew; Burns, Graham; Chaudhuri, Rekha; Chrystyn, Henry; Davies, Lisa; De Soyza, Anthony; Fielding, Shona; Gompertz, Simon; Haughney, John; Lee, Amanda J; McCormack, Kirsty; McPherson, Gladys; Morice, Alyn; Norrie, John; Sullivan, Anita; Wilson, Andrew; Price, David

2015-06-10

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014.

Ghost Authorship in Industry-Initiated Randomised Trials

PubMed Central

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2007-01-01

Background Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. Methods and Findings We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994–1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%–87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%–98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Conclusions Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available. PMID:17227134

Ghost authorship in industry-initiated randomised trials.

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2007-01-01

Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994-1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%-87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%-98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available.

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

PubMed

DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

2011-06-30

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Understanding the acceptability of e-mental health--attitudes and expectations towards computerised self-help treatments for mental health problems.

PubMed

Musiat, Peter; Goldstone, Philip; Tarrier, Nicholas

2014-04-11

E-mental health and m-mental health include the use of technology in the prevention, treatment and aftercare of mental health problems. With the economical pressure on mental health services increasing, e-mental health and m-mental health could bridge treatment gaps, reduce waiting times for patients and deliver interventions at lower costs. However, despite the existence of numerous effective interventions, the transition of computerised interventions into care is slow. The aim of the present study was to investigate the acceptability of e-mental health and m-mental health in the general population. An advisory group of service users identified dimensions that potentially influence an individual's decision to engage with a particular treatment for mental health problems. A large sample (N = 490) recruited through email, flyers and social media was asked to rate the acceptability of different treatment options for mental health problems on these domains. Results were analysed using repeated measures MANOVA. Participants rated the perceived helpfulness of an intervention, the ability to motivate users, intervention credibility, and immediate access without waiting time as most important dimensions with regard to engaging with a treatment for mental health problems. Participants expected face-to-face therapy to meet their needs on most of these dimensions. Computerised treatments and smartphone applications for mental health were reported to not meet participants' expectations on most domains. However, these interventions scored higher than face-to-face treatments on domains associated with the convenience of access. Overall, participants reported a very low likelihood of using computerised treatments for mental health in the future. Individuals in this study expressed negative views about computerised self-help intervention and low likelihood of use in the future. To improve the implementation and uptake, policy makers need to improve the public perception of such interventions.

Understanding the acceptability of e-mental health - attitudes and expectations towards computerised self-help treatments for mental health problems

PubMed Central

2014-01-01

Background E-mental health and m-mental health include the use of technology in the prevention, treatment and aftercare of mental health problems. With the economical pressure on mental health services increasing, e-mental health and m-mental health could bridge treatment gaps, reduce waiting times for patients and deliver interventions at lower costs. However, despite the existence of numerous effective interventions, the transition of computerised interventions into care is slow. The aim of the present study was to investigate the acceptability of e-mental health and m-mental health in the general population. Methods An advisory group of service users identified dimensions that potentially influence an individual’s decision to engage with a particular treatment for mental health problems. A large sample (N = 490) recruited through email, flyers and social media was asked to rate the acceptability of different treatment options for mental health problems on these domains. Results were analysed using repeated measures MANOVA. Results Participants rated the perceived helpfulness of an intervention, the ability to motivate users, intervention credibility, and immediate access without waiting time as most important dimensions with regard to engaging with a treatment for mental health problems. Participants expected face-to-face therapy to meet their needs on most of these dimensions. Computerised treatments and smartphone applications for mental health were reported to not meet participants’ expectations on most domains. However, these interventions scored higher than face-to-face treatments on domains associated with the convenience of access. Overall, participants reported a very low likelihood of using computerised treatments for mental health in the future. Conclusions Individuals in this study expressed negative views about computerised self-help intervention and low likelihood of use in the future. To improve the implementation and uptake, policy makers need to improve the public perception of such interventions. PMID:24725765

Targeted full energy and protein delivery in critically ill patients: a study protocol for a pilot randomised control trial (FEED Trial).

PubMed

Fetterplace, Kate; Deane, Adam M; Tierney, Audrey; Beach, Lisa; Knight, Laura D; Rechnitzer, Thomas; Forsyth, Adrienne; Mourtzakis, Marina; Presneill, Jeffrey; MacIsaac, Christopher

2018-01-01

Current guidelines for the provision of protein for critically ill patients are based on incomplete evidence, due to limited data from randomised controlled trials. The present pilot randomised controlled trial is part of a program of work to expand knowledge about the clinical effects of protein delivery to critically ill patients. The primary aim of this pilot study is to determine whether an enteral feeding protocol using a volume target, with additional protein supplementation, delivers a greater amount of protein and energy to mechanically ventilated critically ill patients than a standard nutrition protocol. The secondary aims are to evaluate the potential effects of this feeding strategy on muscle mass and other patient-centred outcomes. This prospective, single-centred, pilot, randomised control trial will include 60 participants who are mechanically ventilated and can be enterally fed. Following informed consent, the participants receiving enteral nutrition in the intensive care unit (ICU) will be allocated using a randomisation algorithm in a 1:1 ratio to the intervention (high-protein daily volume-based feeding protocol, providing 25 kcal/kg and 1.5 g/kg protein) or standard care (hourly rate-based feeding protocol providing 25 kcal/kg and 1 g/kg protein). The co-primary outcomes are the average daily protein and energy delivered to the end of day 15 following randomisation. The secondary outcomes include change in quadriceps muscle layer thickness (QMLT) from baseline (prior to randomisation) to ICU discharge and other nutritional and patient-centred outcomes. This trial aims to examine whether a volume-based feeding protocol with supplemental protein increases protein and energy delivery. The potential effect of such increases on muscle mass loss will be explored. These outcomes will assist in formulating larger randomised control trials to assess mortality and morbidity. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: 12615000876594 UTN: U1111-1172-8563.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

PubMed

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-04-01

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A quality analysis of clinical anaesthesia study protocols from the Chinese clinical trials registry according to the SPIRIT statement.

PubMed

Yang, Lei; Chen, Shouming; Yang, Di; Li, Jiajin; Wu, Taixiang; Zuo, Yunxia

2018-05-15

To learn about the overall quality of clinical anaesthesia study protocols from the Chinese Clinical Trials Registry and to discuss the way to improve study protocol quality. We defined completeness of each sub-item in SPIRIT as N/A (not applicable) or with a score of 0, 1, or 2. For each protocol, we calculated the proportion of adequately reported items (score = 2 and N/A) and unreported items (score = 0). Protocol quality was determined according to the proportion of reported items, with values >50% indicating high quality. Protocol quality was determined according to the proportion of reported items. For each sub-item in SPIRIT, we calculated the adequately reported rate (percentage of all protocols with score 2 and NA on one sub-item) as well as the unreported rate (percentage of all protocols with score 0 on one sub-item). Total 126 study protocols were available for assessment. Among these, 88.1% were assessed as being of low quality. By comparison, the percentage of low-quality protocols was 88.9% after the publication of the SPIRIT statement. Among the 51 SPIRIT sub-items, 18 sub-items had an unreported rate above 90% while 16 had a higher adequately reported rate than an unreported rate. The overall quality of clinical anaesthesia study protocols registered in the ChiCTR was poor. A mandatory protocol upload and self-check based on the SPIRIT statement during the trial registration process may improve protocol quality in the future.

INRstar: computerised decision support software for anticoagulation management in primary care.

PubMed

Jones, Robert Treharne; Sullivan, Mark; Barrett, David

2005-01-01

Computerised decision support software (CDSS) for anticoagulation management has become established practice in the UK, offering significant advantages for patients and clinicians over traditional methods of dose calculation. The New GMS Contract has been partly responsible for this shift of management from secondary to primary care, in which INRstar has been the market leader for many years. In September 2004, INRstar received the John Perry Prize, awarded by the PHCSG for excellence and innovation in medical applications of information technology.

A comparison of VO2max and metabolic variables between treadmill running and treadmill skating.

PubMed

Koepp, Kriston K; Janot, Jeffrey M

2008-03-01

The purpose of this study was to determine differences in VO2max and metabolic variables between treadmill running and treadmill skating. This study also examined VO2max responses during a continuous skating treadmill protocol and a discontinuous skating treadmill protocol. Sixteen male high school hockey players, who had a mean age of 16 +/- 1 years and were of an above-average fitness level, participated in this study. All subjects completed 4 exercise trials: a 1-hour skating treadmill familiarization trial, a treadmill running trial, and 2 randomized skating treadmill trials. Minute ventilation (VE), oxygen consumption VO2), carbon dioxide production VCO2), respiratory exchange ratio (RER), and heart rate were averaged every 15 seconds up to VO2max for each exercise test. The results showed that there was a significant difference (P < 0.05) for VO2max (mL.kg.min) and maximal VCO2 (L.min) between the running treadmill protocol and discontinuous skating treadmill protocol. There was also a significant difference for maximal RER between the discontinuous and continuous skating treadmill protocol and between the discontinuous skating treadmill protocol and running treadmill protocol. In conclusion, the running treadmill elicited a greater VO2max (mL.kg.min) than the skating treadmill did, but when it comes to specificity of ice skating, the skating treadmill may be ideal. Also, there was no significant difference between the discontinuous and continuous skating treadmill protocols. Therefore, a continuous protocol is possible on the skating treadmill without compromising correct skating position and physiologic responses. However, the continuous skating treadmill protocol should undergo validation before other scientists, coaches, and strength and conditioning professionals can apply it correctly.

Trends in the number and the quality of trial protocols involving children submitted to a French Institutional Review Board.

PubMed

Gautier, Isabelle; Janiaud, Perrine; Rollet, Nelly; André, Nicolas; Tsimaratos, Michel; Cornu, Catherine; Malik, Salma; Gentile, Stéphanie; Kassaï, Behrouz

2017-08-23

There is a great need for high quality clinical research for children. The European Pediatric Regulation aimed to improve the quality of clinical trials in order to increase the availability of treatments for children. The main purpose of this study was to assess the evolution of both the number and the quality of pediatric trial protocols that were submitted to a French Institutional Review Board (IRB00009118) before and after the initiation of the EU Pediatric Regulation. All protocols submitted to the IRB00009118 between 2003 and 2014 and conducting research on subjects under eighteen years of age were eligible. The quality of randomized clinical trials was assessed according to the guidelines developed by the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network and ranked using the Jadad score. Out of 622 protocols submitted to the Institutional Review Board (IRB), 21% (133/622) included children. Among these 133 pediatric protocols, the number of submitted pediatric protocols doubled between the two studied periods. From 2003 to 2008, 47 protocols including 21 institutionally sponsored were submitted to the IRB and from 2009 until 2014, 86 protocols including 48 institutionally sponsored were submitted. No significant trend was observed on the quality of RCTs. The overall median score of RCTs on the Jadad scale was high (3.5), 70.0% of protocols had a Jadad score ≥ 3, and 30.0% had a score < 3. Following the EU Pediatric Regulation, the number of pediatric protocols submitted to the IRB00009118 tends to increase, but no change was noticed regarding their quality.

Dual sensory loss: development of a dual sensory loss protocol and design of a randomized controlled trial

PubMed Central

2013-01-01

Background Dual sensory loss (DSL) has a negative impact on health and wellbeing and its prevalence is expected to increase due to demographic aging. However, specialized care or rehabilitation programs for DSL are scarce. Until now, low vision rehabilitation does not sufficiently target concurrent impairments in vision and hearing. This study aims to 1) develop a DSL protocol (for occupational therapists working in low vision rehabilitation) which focuses on optimal use of the senses and teaches DSL patients and their communication partners to use effective communication strategies, and 2) describe the multicenter parallel randomized controlled trial (RCT) designed to test the effectiveness and cost-effectiveness of the DSL protocol. Methods/design To develop a DSL protocol, literature was reviewed and content was discussed with professionals in eye/ear care (interviews/focus groups) and DSL patients (interviews). A pilot study was conducted to test and confirm the DSL protocol. In addition, a two-armed international multi-center RCT will evaluate the effectiveness and cost-effectiveness of the DSL protocol compared to waiting list controls, in 124 patients in low vision rehabilitation centers in the Netherlands and Belgium. Discussion This study provides a treatment protocol for rehabilitation of DSL within low vision rehabilitation, which aims to be a valuable addition to the general low vision rehabilitation care. Trial registration Netherlands Trial Register (NTR) identifier: NTR2843 PMID:23941667

Young people with higher social anxiety are less likely to adopt the perspective of another: Data from the Director task.

PubMed

Pile, Victoria; Haller, Simone P W; Hiu, Chii Fen; Lau, Jennifer Y F

2017-06-01

Young people with social anxiety display poor social functioning but it is unclear whether this is underscored by difficulties in key social cognitive abilities, such as perspective taking. Here, we examined whether increased social anxiety is associated with reduced accuracy on a perspective taking task and whether this relationship is stronger at particular periods within adolescence. Fifty-nine adolescents aged 11-19 years completed the computerised Director Task (DT) and the Social Anxiety Scale for Adolescence. In the DT, participants virtually move objects by following either instructions given by the 'Director' (who can see only some objects), or a simple rule to ignore certain objects. Participants who scored above the clinical cut-off for social anxiety (n = 17) were less accurate when they had to take the perspective of the Director into account than those scoring below cut-off, yet performed similarly on control trials. Preliminary analysis indicated that poorer performance was most strongly associated with social anxiety in mid-adolescence (14-16.5 years). The DT has been used previously to measure online perspective taking but the underlying cognitive mechanisms have not been fully elucidated. Extending these findings using additional measures of perspective taking would be valuable. Adolescents with higher social anxiety were less accurate at taking the perspective of a computerised character, with some suggestion that this relationship is strongest during mid-adolescence. If replicated, these findings highlight the importance of addressing specific social cognitive abilities in the assessment and treatment of adolescent social anxiety. Copyright © 2016. Published by Elsevier Ltd.

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis.

PubMed

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-04-12

Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. NCT023528702; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Variability among electronic cigarettes in the pressure drop, airflow rate, and aerosol production.

PubMed

Williams, Monique; Talbot, Prue

2011-12-01

This study investigated the performance of electronic cigarettes (e-cigarettes), compared different models within a brand, compared identical copies of the same model within a brand, and examined performance using different protocols. Airflow rate required to generate aerosol, pressure drop across e-cigarettes, and aerosol density were examined using three different protocols. First 10 puff protocol: The airflow rate required to produce aerosol and aerosol density varied among brands, while pressure drop varied among brands and between the same model within a brand. Total air hole area correlated with pressure drop for some brands. Smoke-out protocol: E-cigarettes within a brand generally performed similarly when puffed to exhaustion; however, there was considerable variation between brands in pressure drop, airflow rate required to produce aerosol, and the total number of puffs produced. With this protocol, aerosol density varied significantly between puffs and gradually declined. CONSECUTIVE TRIAL PROTOCOL: Two copies of one model were subjected to 11 puffs in three consecutive trials with breaks between trials. One copy performed similarly in each trial, while the second copy of the same model produced little aerosol during the third trial. The different performance properties of the two units were attributed to the atomizers. There was significant variability between and within brands in the airflow rate required to produce aerosol, pressure drop, length of time cartridges lasted, and production of aerosol. Variation in performance properties within brands suggests a need for better quality control during e-cigarette manufacture.

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service.

PubMed

Debruyne, Philip R; Johnson, Philip J; Pottel, Lies; Daniels, Susanna; Greer, Rachel; Hodgkinson, Elizabeth; Kelly, Stephen; Lycke, Michelle; Samol, Jens; Mason, Julie; Kimber, Donna; Loucaides, Eileen; Parmar, Mahesh Kb; Harvey, Sally

2015-06-01

Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research. © The Author(s) 2015.

Oncosurgical Management of Liver Limited Stage IV Colorectal Cancer: Preliminary Data and Protocol for a Randomized Controlled Trial.

PubMed

Sutton, Paul; Vimalachandran, Dale; Poston, Graeme; Fenwick, Stephen; Malik, Hassan

2018-05-09

Colorectal cancer is the fourth commonest cancer and second commonest cause of cancer-related death in the United Kingdom. Almost 15% of patients have metastases on presentation. An increasing number of surgical strategies and better neoadjuvant treatment options are responsible for more patients undergoing resection of liver metastases, with prolonged survival in a select group of patients who present with synchronous disease. It is clear that the optimal strategy for the management of these patients remains unclear, and there is certainly a complete absence of Level 1 evidence in the literature. The objective of this study is to undertake preliminary work and devise an outline trial protocol to inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We have undertaken some preliminary work and begun the process of designing a randomized controlled trial and present a draft trial protocol here. This study is at the protocol development stage only, and as such no results are available. There is no funding in place for this study, and no anticipated start date. We have presented preliminary work and an outline trial protocol which we anticipate will inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We do not believe that the trial we have designed will answer the most significant clinical questions, nor that it is feasible to be delivered within the United Kingdom's National Health Service at this current time. ©Paul Sutton, Dale Vimalachandran, Graeme Poston, Stephen Fenwick, Hassan Malik. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.05.2018.

A quality analysis of clinical anaesthesia study protocols from the Chinese clinical trials registry according to the SPIRIT statement

PubMed Central

Yang, Lei; Chen, Shouming; Yang, Di; Li, Jiajin; Wu, Taixiang; Zuo, Yunxia

2018-01-01

Objective To learn about the overall quality of clinical anaesthesia study protocols from the Chinese Clinical Trials Registry and to discuss the way to improve study protocol quality. Methods We defined completeness of each sub-item in SPIRIT as N/A (not applicable) or with a score of 0, 1, or 2. For each protocol, we calculated the proportion of adequately reported items (score = 2 and N/A) and unreported items (score = 0). Protocol quality was determined according to the proportion of reported items, with values >50% indicating high quality. Protocol quality was determined according to the proportion of reported items. For each sub-item in SPIRIT, we calculated the adequately reported rate (percentage of all protocols with score 2 and NA on one sub-item) as well as the unreported rate (percentage of all protocols with score 0 on one sub-item). Results Total 126 study protocols were available for assessment. Among these, 88.1% were assessed as being of low quality. By comparison, the percentage of low-quality protocols was 88.9% after the publication of the SPIRIT statement. Among the 51 SPIRIT sub-items, 18 sub-items had an unreported rate above 90% while 16 had a higher adequately reported rate than an unreported rate. Conclusions The overall quality of clinical anaesthesia study protocols registered in the ChiCTR was poor. A mandatory protocol upload and self-check based on the SPIRIT statement during the trial registration process may improve protocol quality in the future. PMID:29872509

Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

PubMed

Sevransky, Jonathan E; Checkley, William; Herrera, Phabiola; Pickering, Brian W; Barr, Juliana; Brown, Samuel M; Chang, Steven Y; Chong, David; Kaufman, David; Fremont, Richard D; Girard, Timothy D; Hoag, Jeffrey; Johnson, Steven B; Kerlin, Mehta P; Liebler, Janice; O'Brien, James; O'Keefe, Terence; Park, Pauline K; Pastores, Stephen M; Patil, Namrata; Pietropaoli, Anthony P; Putman, Maryann; Rice, Todd W; Rotello, Leo; Siner, Jonathan; Sajid, Sahul; Murphy, David J; Martin, Greg S

2015-10-01

Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. A total of 6,179 critically ill patients. Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. None. The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15-21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

[Development of clinical trial education program for pharmaceutical science students through small group discussion and role-playing using protocol].

PubMed

Imakyure, Osamu; Shuto, Hideki; Nishikawa, Fumi; Hagiwara, Yoshifuka; Inoue, Sachiko; Koyanagi, Taeko; Hirakawa, Masaaki; Kataoka, Yasufumi

2010-08-01

The acquirement of basic knowledge of clinical trials and professional attitude in their practices is a general instructional objective in the Model Core Curriculum for Pharmaceutical Education. Unfortunately, the previous program of clinical trial education was not effective in the acquirement of a professional attitude in their practices. Then, we developed the new clinical trial education program using protocol through small group discussion (SGD) and roll-playing. Our program consists of 7 steps of practical training. In step 1, the students find some problems after presentation of the protocol including case and prescription. In step 2, they analyse the extracted problems and share the information obtained in SGD. In steps 3 and 5, five clinical case scenarios are presented to the students and they discuss which case is suitable for entry to the clinical trial or which case corresponds to the discontinuance criteria in the present designed protocol. In steps 4 and 6, the roll-playing is performed by teachers and students as doctors and clinical research coordinators (CRC) respectively. Further, we conducted a trial practice based on this program for the students. In the student's self-evaluation into five grades, the average score of the skill acquisition level in each step was 3.8-4.7 grade. Our clinical trial education program could be effective in educating the candidates for CRC or clinical pharmacists.

Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration

PubMed Central

Shadmehr, Reza; Ohminami, Shinya; Tsutsumi, Ryosuke; Shirota, Yuichiro; Shimizu, Takahiro; Tanaka, Nobuyuki; Terao, Yasuo; Tsuji, Shoji; Ugawa, Yoshikazu; Uchimura, Motoaki; Inoue, Masato; Kitazawa, Shigeru

2015-01-01

Cerebellar damage can profoundly impair human motor adaptation. For example, if reaching movements are perturbed abruptly, cerebellar damage impairs the ability to learn from the perturbation-induced errors. Interestingly, if the perturbation is imposed gradually over many trials, people with cerebellar damage may exhibit improved adaptation. However, this result is controversial, since the differential effects of gradual vs. abrupt protocols have not been observed in all studies. To examine this question, we recruited patients with pure cerebellar ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled, making it possible to impose the full perturbation abruptly in one trial, or build up the perturbation gradually over many trials. To control visual feedback, we employed shutter glasses that removed visual feedback during the reach, allowing us to measure trial-by-trial learning from error (termed error-sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We found that the patients benefited significantly from the gradual protocol, improving their performance with respect to the abrupt protocol by exhibiting smaller errors during the exposure block, and producing larger aftereffects during the postexposure block. Trial-by-trial analysis suggested that this improvement was due to increased error-sensitivity in the gradual protocol. Therefore, cerebellar patients exhibited an improved ability to learn from error if they experienced those errors gradually. This improvement coincided with increased error-sensitivity and was present in both groups of subjects, suggesting that control of error-sensitivity may be spared despite cerebellar damage. PMID:26311179

Application of computerised penile arterial waveform analysis in the diagnosis of arteriogenic impotence. An initial study in potent and impotent men.

PubMed

Desai, K M; Gingell, J C; Skidmore, R; Follett, D H

1987-11-01

A new method is described for evaluating arteriogenic impotence by means of noninvasive quantification of penile Doppler arterial waveforms using computerised analysis based on the Laplace Transform model. The haemodynamic changes occurring during a papaverine-induced erection in healthy potent volunteers have been recorded by this technique, which has also been shown to be capable of discriminating between a normal and an abnormal penile arterial supply in an initial study of potent and impotent men.

Comparison of two progressive treadmill tests in patients with peripheral arterial disease.

PubMed

Riebe, D; Patterson, R B; Braun, C M

2001-11-01

In a vascular rehabilitation program, 28% of our frail elderly patients are unable to be tested with traditional progressive exercise protocols at program entry due to the high (2.0 miles/h or 3.2 km/h) initial treadmill speeds. The purpose of this investigation was to compare a new progressive treadmill protocol which has a reduced initial speed (1.0 mile/h or 1.6 km/h) to an established protocol performed at 2.0 miles/h (3.2 km/h) to determine the comparability and reproducibility of the new protocol. Eleven patients with arterial claudication performed three symptom-limited exercise tests in random order. Two tests used the new protocol while the remaining trial used the established protocol. Claudication pain was measured using a 5-point scale. Oxygen consumption, heart rate, minute ventilation, respiratory exchange ratio and blood pressure at peak exercise were similar among the three trials. There were strong intraclass correlations for peak oxygen consumption (r = 0.97), onset of claudication (r = 0.96) and maximum walking time (r = 0.98) between the two trials using the new protocol. There was also a significant correlation between the new protocol and the established protocol for peak oxygen consumption (r = 0.90) and maximum walking time (r = 0.89). The new progressive treadmill protocol represents a valid, reliable protocol for patients with arterial claudication. This protocol may be useful for testing patients with a low functional capacity so that clinically appropriate exercise prescriptions can be established and the efficacy of treatments can be determined.

A randomized trial of protocol-based care for early septic shock.

PubMed

Yealy, Donald M; Kellum, John A; Huang, David T; Barnato, Amber E; Weissfeld, Lisa A; Pike, Francis; Terndrup, Thomas; Wang, Henry E; Hou, Peter C; LoVecchio, Frank; Filbin, Michael R; Shapiro, Nathan I; Angus, Derek C

2014-05-01

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support. We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.

PubMed

Llewellyn-Bennett, Rebecca; Bowman, Louise; Bulbulia, Richard

2016-12-15

Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials. A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial. Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs. Not applicable for PROSPERO registration.

Protocols and Hospital Mortality in Critically ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study

PubMed Central

Sevransky, Jonathan E.; Checkley, William; Herrera, Phabiola; Pickering, Brian W.; Barr, Juliana; Brown, Samuel M; Chang, Steven Y; Chong, David; Kaufman, David; Fremont, Richard D; Girard, Timothy D; Hoag, Jeffrey; Johnson, Steven B; Kerlin, Mehta P; Liebler, Janice; O'Brien, James; O'Keefe, Terence; Park, Pauline K; Pastores, Stephen M; Patil, Namrata; Pietropaoli, Anthony P; Putman, Maryann; Rice, Todd W.; Rotello, Leo; Siner, Jonathan; Sajid, Sahul; Murphy, David J; Martin, Greg S

2015-01-01

Objective Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized intensive care units have superior patient outcomes compared with less highly protocolized intensive care units. Design Observational study in which participating intensive care units completed a general assessment and enrolled new patients one day each week. Setting and Patients 6179 critically ill patients across 59 intensive care units in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study Interventions: None Measurements and Main Results The primary exposure was the number of intensive care unit protocols; the primary outcome was hospital mortality. 5809 participants were followed prospectively and 5454 patients in 57 intensive care units had complete outcome data. The median number of protocols per intensive care unit was 19 (IQR 15 to 21.5). In single variable analyses, there were no differences in intensive care unit and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in intensive care units with a high vs. low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p=0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between intensive care units with high vs. low numbers of protocols for lung protective ventilation in ARDS (47% vs. 52%; p=0.28) and for spontaneous breathing trials (55% vs. 51%; p=0.27). Conclusions Clinical protocols are highly prevalent in United States intensive care units. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality. PMID:26110488

The design, construction and implementation of a computerised trauma registry in a developing South African metropolitan trauma service.

PubMed

Laing, G L; Bruce, J L; Aldous, C; Clarke, D L

2014-01-01

The Pietermaritzburg Metropolitan Trauma Service formerly lacked a robust computerised trauma registry. This made surgical audit difficult for the purpose of quality of care improvement and development. We aimed to design, construct and implement a computerised trauma registry within our service. Twelve months following its implementation, we sought to examine and report on the quality of the registry. Formal ethical approval to maintain a computerised trauma registry was obtained prior to undertaking any design and development. Appropriate commercial software was sourced to develop this project. The registry was designed as a flat file. A flat file is a plain text or mixed text and binary file which usually contains one record per line or physical record. Thereafter the registry file was launched onto a secure server. This provided the benefits of access security and automated backups. Registry training was provided to clients by the developer. The exercise of data capture was then integrated into the process of service delivery, taking place at the endpoint of patient care (discharge, transfer or death). Twelve months following its implementation, the compliance rates of data entry were measured. The developer of this project managed to design, construct and implement an electronic trauma registry into the service. Twelve months following its implementation the data were extracted and audited to assess the quality. A total of 2640 patient entries were captured onto the registry. Compliance rates were in the order of eighty percent and client satisfaction rates were high. A number of deficits were identified. These included the omission of weekend discharges and underreporting of deaths. The construction and implementation of the computerised trauma registry was the beginning of an endeavour to continue improvements in the quality of care within our service. The registry provided a reliable audit at twelve months post implementation. Deficits and limitations were identified and new strategies have been planned to overcome these problems and integrate the trauma registry into the process of clinical care. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial.

PubMed

Hershberg, Julie A; Rose, Dorian K; Tilson, Julie K; Brutsch, Bettina; Correa, Anita; Gallichio, Joann; McLeod, Molly; Moore, Craig; Wu, Sam; Duncan, Pamela W; Behrman, Andrea L

2017-01-01

Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice. Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making. In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation. Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).

Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

2016-03-22

To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

Randomised controlled trial to evaluate the efficacy and usability of a computerised phone-based lifestyle coaching system for primary and secondary prevention of stroke.

PubMed

Spassova, Lübomira; Vittore, Debora; Droste, Dirk W; Rösch, Norbert

2016-02-09

One of the most effective current approaches to preventing stroke events is the reduction of lifestyle risk factors, such as unhealthy diet, physical inactivity and smoking. In this study, we assessed the efficacy and usability of the phone-based Computer-aided Prevention System (CAPSYS) in supporting the reduction of lifestyle-related risk factors. A single-centre two-arm clinical trial was performed between January 2013 and February 2014, based on individual follow-up periods of six months with 94 patients at high risk of stroke, randomly assigned to an intervention group (IC: 48; advised to use the CAPSYS system) or a standard care group (SC: 46). Study parameters, such as blood pressure, blood values (HDL, LDL, HbA1c, glycaemia and triglycerides), weight, height, physical activity as well as nutrition and smoking habits were captured through questionnaires and medical records at baseline and post-intervention and analysed to detect significant changes. The usability of the intervention was assessed based on the standardised System Usability Scale (SUS) complemented by a more system-specific user satisfaction and feedback questionnaire. The statistical evaluation of primary measures revealed significant decreases of systolic blood pressure (mean of the differences = -9 mmHg; p = 0.03; 95% CI = [-17.29, -0.71]), LDL (pseudo-median of the differences = -7.9 mg/dl; p = 0.04; 95% CI = [-18.5, -0.5]) and triglyceride values (pseudo-median of the differences = -12.5 mg/dl; p = 0.04; 95% CI = [-26, -0.5]) in the intervention group, while no such changes could be observed in the control group. Furthermore, we detected a statistically significant increase in self-reported fruit and vegetable consumption (pseudo-median of the differences = 5.4 servings/week; p = 0.04; 95% CI = [0.5, 10.5]) and a decrease in sweets consumption (pseudo-median of the differences = -2 servings/week; p = 0.04; 95% CI = [-4, -0.00001]) in the intervention group. The usability assessment showed that the CAPSYS system was, in general, highly accepted by the users (average SUS score: 80.1). The study provided encouraging results indicating that a computerised phone-based lifestyle coaching system, such as CAPSYS, can support the usual treatment in reducing cerebro-cardiovascular risk factors and that such an approach is well applicable in practice. ClinicalTrials.gov Identifier: NCT02444715.

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

PubMed Central

Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

2015-01-01

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

Features Associated with Successful Recruitment of Diverse Patients onto Cancer Clinical Trials: Report from the American College of Surgeons Oncology Group

PubMed Central

Diehl, Kathleen M.; Green, Erin M.; Weinberg, Armin; Frederick, Wayne A.; Holmes, Dennis R.; Green, Bettye; Morris, Arden; Kuerer, Henry M.; Beltran, Robert A.; Mendez, Jane; Gines, Venus; Ota, David M.; Nelson, Heidi; Newman, Lisa A.

2018-01-01

Background The clinical trials mechanism of standardized treatment and follow-up for cancer patients with similar stages and patterns of disease is the most powerful approach available for evaluating the efficacy of novel therapies, and clinical trial participation should protect against delivery of care variations associated with racial/ethnic identity and/or socioeconomic status. Unfortunately, disparities in clinical trial accrual persist, with African Americans (AA) and Hispanic/Latino Americans (HA) underrepresented in most studies. Study Design We evaluated the accrual patterns for ten clinical trials conducted by the American College of Surgeons Oncology Group (ACOSOG) 1999–2009, and analyzed results by race/ethnicity as well as study design. Results Eight of ten protocols were successful in recruiting AA and/or HA participants; three of four randomized trials were successful. Features that were present among all of the successfully-recruiting protocols were: (i) studies designed to recruit patients with regional or advanced-stage disease (2/2 protocols); and (ii) studies that involved some investigational systemic therapy (3/3 protocols). Discussion AA and HA cancer patients can be successfully accrued onto randomized clinical trials, but study design affects recruitment patterns. Increased socioeconomic disadvantages observed within minority-ethnicity communities results in barriers to screening and more advanced cancer stage distribution. Improving cancer early detection is critical in the effort to eliminate outcome disparities but existing differences in disease burden results in diminished eligibility for early-stage cancer clinical trials among minority-ethnicity patients. PMID:21681382

Effects of early augmentation of labour with amniotomy and oxytocin in nulliparous women: a meta-analysis.

PubMed

Fraser, W; Vendittelli, F; Krauss, I; Bréart, G

1998-02-01

To estimate the effects among nulliparae of early augmentation with amniotomy and oxytocin on caesarean delivery, and on other indicators of maternal and neonatal morbidity including transfusion. Apgar score < 7 at 5 minutes, and admission to the special care nursery. Meta-analysis. Published studies were identified through manual and computerised searches. Two unpublished studies were identified through direct communication with the investigators. Twelve trials were identified which compared a policy of early labour augmentation including amniotomy followed by oxytocin with a less active form of management. Two methodologically unacceptable studies were excluded. Studies were grouped according to whether they admitted only women with abnormal progress (therapy trials: n = 3) or accepted women with normal labour (prevention trials: n = 7). Unstratified analysis did not provide support for the hypothesis that early augmentation reduces the risk of caesarean section (typical odds ratio [OR] 0.9; 95% CI 0.7-1.1). The typical odds ratio for prevention trials was similar to that obtained in the unstratified analysis (typical OR 0.9, 95% CI 0.7-1.2). Although only a small number of women have been randomised in therapy trials, a trend toward a reduction in the rate of caesarean section with early intervention was seen in this group (typical OR 0.6, 95% CI 0.2-1.4). Early augmentation does not appear to provide benefit over a more conservative form of management in the context of care of nulliparous women with mild delays in the progress of labour. In the context of established delay in labour, an active policy of augmentation may reduce the risk of caesarean section. However, only three small trials have been performed in this context, and they do not have adequate power to allow firm conclusions to be drawn.

Reporting of methods was better in the Clinical Trials Registry-India than in Indian journal publications.

PubMed

Tharyan, Prathap; George, Aneesh Thomas; Kirubakaran, Richard; Barnabas, Jabez Paul

2013-01-01

We sought to evaluate if editorial policies and the reporting quality of randomized controlled trials (RCTs) had improved since our 2004-05 survey of 151 RCTs in 65 Indian journals, and to compare reporting quality of protocols in the Clinical Trials Registry-India (CTRI). An observational study of endorsement of Consolidated Standards for the Reporting of Trials (CONSORT) and International Committee of Medical Journal Editors (ICMJE) requirements in the instructions to authors in Indian journals, and compliance with selected requirements in all RCTs published during 2007-08 vs. our previous survey and between all RCT protocols in the CTRI on August 31, 2010 and published RCTs from both surveys. Journal policies endorsing the CONSORT statement (22/67, 33%) and ICMJE requirements (35/67, 52%) remained suboptimal, and only 4 of 13 CONSORT items were reported in more than 50% of the 145 RCTs assessed. Reporting of ethical issues had improved significantly, and that of methods addressing internal validity had not improved. Adequate methods were reported significantly more frequently in 768 protocols in the CTRI, than in the 296 published trials. The CTRI template facilitates the reporting of valid methods in registered trial protocols. The suboptimal compliance with CONSORT and ICMJE requirements in RCTs published in Indian journals reduces credibility in the reliability of their results. Copyright © 2013 Elsevier Inc. All rights reserved.

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Moler, Frank W; Silverstein, Faye S; Meert, Kathleen L; Clark, Amy E; Holubkov, Richard; Browning, Brittan; Slomine, Beth S; Christensen, James R; Dean, J Michael

2013-09-01

To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Multicenter randomized controlled trials. Pediatric intensive care and cardiac ICUs in the United States and Canada. Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Therapeutic hypothermia or therapeutic normothermia. From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

Update in mild traumatic brain injury.

PubMed

Freire-Aragón, María Dolores; Rodríguez-Rodríguez, Ana; Egea-Guerrero, Juan José

2017-08-10

There has been concern for many years regarding the identification of patients with mild traumatic brain injury (TBI) at high risk of developing an intracranial lesion (IL) that would require neurosurgical intervention. The small percentage of patients with these characteristics and the exceptional mortality associated with mild TBI with IL have led to the high use of resources such as computerised tomography (CT) being reconsidered. The various protocols developed for the management of mild TBI are based on the identification of risk factors for IL, which ultimately allows more selective indication or discarding both the CT application and the hospital stay for neurological monitoring. Finally, progress in the study of brain injury biomarkers with prognostic utility in different clinical categories of TBI has recently been incorporated by several clinical practice guidelines, which has allowed, together with clinical assessment, a more accurate prognostic approach for these patients to be established. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Blockchain protocols in clinical trials: Transparency and traceability of consent.

PubMed

Benchoufi, Mehdi; Porcher, Raphael; Ravaud, Philippe

2017-01-01

Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a consistent step toward reproducibility.

Blockchain protocols in clinical trials: Transparency and traceability of consent

PubMed Central

Benchoufi, Mehdi; Porcher, Raphael; Ravaud, Philippe

2018-01-01

Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a consistent step toward reproducibility. PMID:29167732

Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications.

PubMed

De Placido, S; De Angelis, C; Giuliano, M; Pizzi, C; Ruocco, R; Perrone, V; Bruzzese, D; Tommasielli, G; De Laurentiis, M; Cammarota, S; Arpino, G; Arpino, G

2017-03-14

Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays ('routine tests'), and costs was unchanged. However, the number of CT, PET scans and MRI ('new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (P<0.0001). New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

Involving American Indians and medically underserved rural populations in cancer clinical trials.

PubMed

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Fox Dunn, Emily; Patnaik, Asha

2009-12-01

To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7-11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69-75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4-7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3-16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5-17%). Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group.

Involving American Indians and medically underserved rural populations in cancer clinical trials

PubMed Central

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Dunn, Emily Fox; Patnaik, Asha

2010-01-01

Purpose To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. Methods We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Results Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7–11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69–75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4–7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3–16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5–17%). Limitations Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Conclusion Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group. PMID:19933720

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT)

PubMed Central

Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-01

Introduction Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. Methods and analysis A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver ‘active’ interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to ‘active’ intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. Ethics and dissemination The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. Trial registration number ISRCTN 71002650; Pre-results. PMID:26781504

The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation.

PubMed

Lelijveld, Natasha; Bailey, Jeanette; Mayberry, Amy; Trenouth, Lani; N'Diaye, Dieynaba S; Haghparast-Bidgoli, Hassan; Puett, Chloe

2018-04-24

Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. ISRCTN 30393230 , date: 16/03/2017.

Results of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial.

PubMed

Jameson, Michael G; McNamara, Jo; Bailey, Michael; Metcalfe, Peter E; Holloway, Lois C; Foo, Kerwyn; Do, Viet; Mileshkin, Linda; Creutzberg, Carien L; Khaw, Pearly

2016-08-01

Protocol deviations in Randomised Controlled Trials have been found to result in a significant decrease in survival and local control. In some cases, the magnitude of the detrimental effect can be larger than the anticipated benefits of the interventions involved. The implementation of appropriate quality assurance of radiotherapy measures for clinical trials has been found to result in fewer deviations from protocol. This paper reports on a benchmarking study conducted in preparation for the PORTEC-3 trial in Australasia. A benchmarking CT dataset was sent to each of the Australasian investigators, it was requested they contour and plan the case according to trial protocol using local treatment planning systems. These data was then sent back to Trans-Tasman Oncology Group for collation and analysis. Thirty three investigators from eighteen institutions across Australia and New Zealand took part in the study. The mean clinical target volume (CTV) volume was 383.4 (228.5-497.8) cm(3) and the mean dose to a reference gold standard CTV was 48.8 (46.4-50.3) Gy. Although there were some large differences in the contouring of the CTV and its constituent parts, these did not translate into large variations in dosimetry. Where individual investigators had deviations from the trial contouring protocol, feedback was provided. The results of this study will be used to compare with the international study QA for the PORTEC-3 trial. © 2016 The Royal Australian and New Zealand College of Radiologists.

Computerised pathology test order entry reduces laboratory turnaround times and influences tests ordered by hospital clinicians: a controlled before and after study

PubMed Central

Westbrook, J I; Georgiou, A; Dimos, A; Germanos, T

2006-01-01

Objective To assess the impact of a computerised pathology order entry system on laboratory turnaround times and test ordering within a teaching hospital. Methods A controlled before and after study compared test assays ordered from 11 wards two months before (n = 97 851) and after (n = 113 762) the implementation of a computerised pathology order entry system (Cerner Millennium Powerchart). Comparisons were made of laboratory turnaround times, frequency of tests ordered and specimens taken, proportions of patients having tests, average number per patient, and percentage of gentamicin and vancomycin specimens labelled as random. Results Intervention wards experienced an average decrease in turnaround of 15.5 minutes/test assay (range 73.8 to 58.3 minutes; p<0.001). Reductions were significant for prioritised and non‐prioritised tests, and for those done within and outside business hours. There was no significant change in the average number of tests (p = 0.228), or specimens per patient (p = 0.324), and no change in turnaround time for the control ward (p = 0.218). Use of structured order screens enhanced data provided to laboratories. Removing three test assays from the liver function order set resulted in significantly fewer of these tests being done. Conclusions Computerised order entry systems are an important element in achieving faster test results. These systems can influence test ordering patterns through structured order screens, manipulation of order sets, and analysis of real time data to assess the impact of such changes, not possible with paper based systems. The extent to which improvements translate into improved patient outcomes remains to be determined. A potentially limiting factor is clinicians' capacity to respond to, and make use of, faster test results. PMID:16461564

Practices to prevent venous thromboembolism: a brief review

PubMed Central

Lau, Brandyn D; Haut, Elliott R

2014-01-01

Background Venous thromboembolism (VTE) is a common cause of preventable harm for hospitalised patients. Over the past decade, numerous intervention types have been implemented in attempts to improve the prescription of VTE prophylaxis in hospitals, with varying degrees of success. We reviewed key articles to assess the efficacy of different types of interventions to improve prescription of VTE prophylaxis for hospitalised patients. Methods We conducted a search of MEDLINE for key studies published between 2001 and 2012 of interventions employing education, paper based tools, computerised tools, real time audit and feedback, or combinations of intervention types to improve prescription of VTE prophylaxis for patients in hospital settings. Process outcomes of interest were prescription of any VTE prophylaxis and best practice VTE prophylaxis. Clinical outcomes of interest were any VTE and potentially preventable VTE, defined as VTE occurring in patients not prescribed appropriate prophylaxis. Results 16 articles were included in this review. Two studies employed education only, four implemented paper based tools, four used computerised tools, two evaluated audit and feedback strategies, and four studies used combinations of intervention types. Individual modalities result in improved prescription of VTE prophylaxis; however, the greatest and most sustained improvements were those that combined education with computerised tools. Conclusions Many intervention types have proven effective to different degrees in improving VTE prevention. Provider education is likely a required additional component and should be combined with other intervention types. Active mandatory tools are likely more effective than passive ones. Information technology tools that are well integrated into provider workflow, such as alerts and computerised clinical decision support, can improve best practice prophylaxis use and prevent patient harm resulting from VTE. PMID:23708438

Lessons from the Johns Hopkins Multi-Disciplinary Venous Thromboembolism (VTE) Prevention Collaborative

PubMed Central

Streiff, Michael B; Carolan, Howard T; Hobson, Deborah B; Kraus, Peggy S; Holzmueller, Christine G; Demski, Renee; Lau, Brandyn D; Biscup-Horn, Paula; Pronovost, Peter J

2012-01-01

Problem Venous thromboembolism (VTE) is a common cause of potentially preventable mortality, morbidity, and increased medical costs. Risk-appropriate prophylaxis can prevent most VTE events, but only a small fraction of patients at risk receive this treatment. Design Prospective quality improvement programme. Setting Johns Hopkins Hospital, Baltimore, Maryland, USA. Strategies for change A multidisciplinary team established a VTE Prevention Collaborative in 2005. The collaborative applied the four step TRIP (translating research into practice) model to develop and implement a mandatory clinical decision support tool for VTE risk stratification and risk-appropriate VTE prophylaxis for all hospitalised adult patients. Initially, paper based VTE order sets were implemented, which were then converted into 16 specialty-specific, mandatory, computerised, clinical decision support modules. Key measures for improvement VTE risk stratification within 24 hours of hospital admission and provision of risk-appropriate, evidence based VTE prophylaxis. Effects of change The VTE team was able to increase VTE risk assessment and ordering of risk-appropriate prophylaxis with paper based order sets to a limited extent, but achieved higher compliance with a computerised clinical decision support tool and the data feedback which it enabled. Risk-appropriate VTE prophylaxis increased from 26% to 80% for surgical patients and from 25% to 92% for medical patients in 2011. Lessons learnt A computerised clinical decision support tool can increase VTE risk stratification and risk-appropriate VTE prophylaxis among hospitalised adult patients admitted to a large urban academic medical centre. It is important to ensure the tool is part of the clinician’s normal workflow, is mandatory (computerised forcing function), and offers the requisite modules needed for every clinical specialty. PMID:22718994

Evaluating and improving recruitment and retention in an mHealth clinical trial: an example of iterating methods during a trial.

PubMed

Pfammatter, Angela Fidler; Mitsos, Alexa; Wang, Shirlene; Hood, Susan Hammett; Spring, Bonnie

2017-01-01

Recruitment and retention strategy investigations in mHealth clinical trials are rare. Technology presents an opportunity to intensely and remotely evaluate recruitment, use of mobile apps, and retention, leading to new insights for continuous improvement of mHealth trials. The objective of this paper is to present a case study in which a trial evaluated and changed strategies during a clinical trial to improve recruitment, adherence to study protocols, and retention in the mHealth trial. In Fall 2015, the NUYou trial enrolled 150 college freshmen in an mHealth protocol. Three months after study initiation, NUYou struggled to meet recruitment goals and maintain anticipated usage levels of the study smartphone application. Two sets of data were collected to improve recruitment and retention: a survey about recruitment was sent to the target population and surveys regarding usability of the app was sent to the study sample. Survey results informed improvements in recruitment strategies, the study retention protocol, and the smartphone application. Survey results revealed several insights including misunderstanding components of the trial by potential participants, low perceived usefulness of the app, and little recall or impact of the incentive structure. After implementation of user-centered improvements, the second cohort of NUYou recruitment in the fall of 2016 produced an equal sample size in 4 weeks less time. Winter quarter of 2016 compared to 2017 demonstrated an improvement in retention via app use and completion of weekly in-app surveys. Recruitment and retention in clinical trials continues to be a critical challenge and mHealth trials may present both unique challenges and opportunities. To our knowledge, this is the first study to describe a systematic evaluation followed by changes and further evaluation to recruitment, use of the mHealth application, adherence to study protocol, and retention during an mHealth clinical trial. Future work should adopt and explicitly study these processes to optimize both enrollment and retention in these types of trials to preserve validity and reliability of research results.

Tailoring implementation strategies for evidence-based recommendations using computerised clinical decision support systems: protocol for the development of the GUIDES tools.

PubMed

Van de Velde, Stijn; Roshanov, Pavel; Kortteisto, Tiina; Kunnamo, Ilkka; Aertgeerts, Bert; Vandvik, Per Olav; Flottorp, Signe

2016-03-05

A computerised clinical decision support system (CCDSS) is a technology that uses patient-specific data to provide relevant medical knowledge at the point of care. It is considered to be an important quality improvement intervention, and the implementation of CCDSS is growing substantially. However, the significant investments do not consistently result in value for money due to content, context, system and implementation issues. The Guideline Implementation with Decision Support (GUIDES) project aims to improve the impact of CCDSS through optimised implementation based on high-quality evidence-based recommendations. To achieve this, we will develop tools that address the factors that determine successful CCDSS implementation. We will develop the GUIDES tools in four steps, using the methods and results of the Tailored Implementation for Chronic Diseases (TICD) project as a starting point: (1) a review of research evidence and frameworks on the determinants of implementing recommendations using CCDSS; (2) a synthesis of a comprehensive framework for the identified determinants; (3) the development of tools for use of the framework and (4) pilot testing the utility of the tools through the development of a tailored CCDSS intervention in Norway, Belgium and Finland. We selected the conservative management of knee osteoarthritis as a prototype condition for the pilot. During the process, the authors will collaborate with an international expert group to provide input and feedback on the tools. This project will provide guidance and tools on methods of identifying implementation determinants and selecting strategies to implement evidence-based recommendations through CCDSS. We will make the GUIDES tools available to CCDSS developers, implementers, researchers, funders, clinicians, managers, educators, and policymakers internationally. The tools and recommendations will be generic, which makes them scalable to a large spectrum of conditions. Ultimately, the better implementation of CCDSS may lead to better-informed decisions and improved care and patient outcomes for a wide range of conditions. PROSPERO, CRD42016033738.

Evolution of practice during the Interventional Management of Stroke III Trial and implications for ongoing trials.

PubMed

Broderick, Joseph P; Palesch, Yuko Y; Demchuk, Andrew M; Yeatts, Sharon D; Khatri, Pooja; Hill, Michael D; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Mazighi, Mikael; Schonewille, Wouter J; Engelter, Stefan T; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Janis, L Scott; Foster, Lydia D; Tomsick, Thomas A

2014-12-01

We explored changes in the patient population and practice of endovascular therapy during the course of the Interventional Management of Stroke (IMS) III Trial. Changes in baseline characteristics, use of baseline CT angiography, treatment times and specifics, and outcomes were compared between the first 4 protocols and the fifth and final protocol. Compared with subjects treated in the first 4 protocol versions (n=610), subjects treated in fifth and final protocol (n=46) were older (75 versus 68 years, P<0.0002) and less likely to have a pretreatment Rankin of 0 (76% versus 89%, P=0.01), were more likely to have a pretreatment CT angiography (65% versus 45%, P=0.009), had quicker median times in the endovascular arm from onset to start of intra-arterial therapy (209 versus 250 minutes, P=0.002) and to reperfusion (269 versus 344 minutes, P<0.0001), had a higher mean dose of total tissue-type plasminogen activator in the endovascular arm (74.0 versus 63.7 mg, P<0.0001), and were less likely to receive intra-arterial tissue-type plasminogen activator as part of the endovascular procedure (16% versus 44%, P=0.015). There were no significant differences in functional and safety outcomes between subjects treated in the 2 treatments arms in either the first 4 protocols or fifth protocol although the small sample size in the fifth protocol provided limited power. Endovascular technology and diagnostic approaches to acute stroke patients changed substantially during the IMS III Trial. Efforts to decrease the time to delivery of endovascular therapy were successful. © 2014 American Heart Association, Inc.

Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial

PubMed Central

Wall, Peter DH; Dickenson, Edward J; Robinson, David; Hughes, Ivor; Realpe, Alba; Hobson, Rachel; Griffin, Damian R; Foster, Nadine E

2016-01-01

Introduction Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility. Methods In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events. Results The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12–26 weeks in 6–10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events. Conclusion PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839). Trial registration number ISRCTN 09754699. PMID:27629405

Development of a dynamic quality assurance testing protocol for multisite clinical trial DCE-CT accreditation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Driscoll, B.; Keller, H.; Jaffray, D.

2013-08-15

Purpose: Credentialing can have an impact on whether or not a clinical trial produces useful quality data that is comparable between various institutions and scanners. With the recent increase of dynamic contrast enhanced-computed tomography (DCE-CT) usage as a companion biomarker in clinical trials, effective quality assurance, and control methods are required to ensure there is minimal deviation in the results between different scanners and protocols at various institutions. This paper attempts to address this problem by utilizing a dynamic flow imaging phantom to develop and evaluate a DCE-CT quality assurance (QA) protocol.Methods: A previously designed flow phantom, capable of producingmore » predictable and reproducible time concentration curves from contrast injection was fully validated and then utilized to design a DCE-CT QA protocol. The QA protocol involved a set of quantitative metrics including injected and total mass error, as well as goodness of fit comparison to the known truth concentration curves. An additional region of interest (ROI) sensitivity analysis was also developed to provide additional details on intrascanner variability and determine appropriate ROI sizes for quantitative analysis. Both the QA protocol and ROI sensitivity analysis were utilized to test variations in DCE-CT results using different imaging parameters (tube voltage and current) as well as alternate reconstruction methods and imaging techniques. The developed QA protocol and ROI sensitivity analysis was then applied at three institutions that were part of clinical trial involving DCE-CT and results were compared.Results: The inherent specificity of robustness of the phantom was determined through calculation of the total intraday variability and determined to be less than 2.2 ± 1.1% (total calculated output contrast mass error) with a goodness of fit (R{sup 2}) of greater than 0.99 ± 0.0035 (n= 10). The DCE-CT QA protocol was capable of detecting significant deviations from the expected phantom result when scanning at low mAs and low kVp in terms of quantitative metrics (Injected Mass Error 15.4%), goodness of fit (R{sup 2}) of 0.91, and ROI sensitivity (increase in minimum input function ROI radius by 146 ± 86%). These tests also confirmed that the ASIR reconstruction process was beneficial in reducing noise without substantially increasing partial volume effects and that vendor specific modes (e.g., axial shuttle) did not significantly affect the phantom results. The phantom and QA protocol were finally able to quickly (<90 min) and successfully validate the DCE-CT imaging protocol utilized at the three separate institutions of a multicenter clinical trial; thereby enhancing the confidence in the patient data collected.Conclusions: A DCE QA protocol was developed that, in combination with a dynamic multimodality flow phantom, allows the intrascanner variability to be separated from other sources of variability such as the impact of injection protocol and ROI selection. This provides a valuable resource that can be utilized at various clinical trial institutions to test conformance with imaging protocols and accuracy requirements as well as ensure that the scanners are performing as expected for dynamic scans.« less

Delivering prevention for alcohol and cannabis using the Internet: a cluster randomised controlled trial.

PubMed

Newton, Nicola C; Andrews, Gavin; Teesson, Maree; Vogl, Laura E

2009-06-01

To establish the efficacy of an internet based prevention program to reduce alcohol and cannabis use in adolescents. A cluster randomised controlled trial was conducted with 764 13-year olds from ten Australian secondary schools in 2007-2008. Half the schools were randomly allocated to the computerised prevention program (n=397), and half to their usual health classes (n=367). The Climate Schools: Alcohol and Cannabis prevention course is facilitated by the internet and consists of novel, evidence-based, curriculum consistent lessons aimed at reducing alcohol and cannabis use. Participants were assessed at baseline, immediately post, and at six months following the intervention. Compared to the control group, students in the intervention group showed significant improvements in alcohol and cannabis knowledge at the end of the course and the six month follow-up. In addition, the intervention group showed a reduction in average weekly alcohol consumption and frequency of cannabis use at the six month follow-up. No differences between groups were found on alcohol expectancies, cannabis attitudes, or alcohol and cannabis related harms. The course is acceptable, scalable and fidelity is assured. It increased knowledge regarding alcohol and cannabis, and decreased use of these drugs.

Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis.

PubMed

Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C

2016-08-01

Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials. We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that "all adverse events were recorded." For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs. In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles.

Rationale, Timeline, Study Design, and Protocol Overview of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials

PubMed Central

Moler, Frank W.; Silverstein, Faye S.; Meert, Kathleen L.; Clark, Amy E.; Holubkov, Richard; Browning, Brittan; Slomine, Beth S.; Christensen, James R.; Dean, Michael

2014-01-01

Objective To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Design Multicenter randomized controlled trials. Setting Pediatric intensive care and cardiac ICUs in the United States and Canada. Patients Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Interventions Therapeutic hypothermia or therapeutic normothermia. Measurements and Main Results From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Conclusions Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials. PMID:23842585

Quality assurance of the SCOPE 1 trial in oesophageal radiotherapy.

PubMed

Wills, Lucy; Maggs, Rhydian; Lewis, Geraint; Jones, Gareth; Nixon, Lisette; Staffurth, John; Crosby, Tom

2017-11-15

SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims: 1. To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial. 2. To support the trial's clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. A detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre's equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins. 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8-67.8cm 3 ; and PTV volumes 221.9-513.3 cm 3 . For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial. Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a result of their participation in the SCOPE1 trial. The SCOPE 1 QA programme outcomes lend support to the trial's clinical conclusions. The range of patient planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource for this to be addressed within future trials. As indicated in questionnaire responses, the QA exercise as a whole has contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of elements of the protocol. The SCOPE1 trial is an International Standard Randomized Controlled Trial, ISRCTN47718479 .

Quality assurance of data collection in the multi-site community randomized trial and prevalence survey of the children's healthy living program.

PubMed

Yamanaka, Ashley; Fialkowski, Marie Kainoa; Wilkens, Lynne; Li, Fenfang; Ettienne, Reynolette; Fleming, Travis; Power, Julianne; Deenik, Jonathan; Coleman, Patricia; Leon Guerrero, Rachael; Novotny, Rachel

2016-09-02

Quality assurance plays an important role in research by assuring data integrity, and thus, valid study results. We aim to describe and share the results of the quality assurance process used to guide the data collection process in a multi-site childhood obesity prevalence study and intervention trial across the US Affiliated Pacific Region. Quality assurance assessments following a standardized protocol were conducted by one assessor in every participating site. Results were summarized to examine and align the implementation of protocol procedures across diverse settings. Data collection protocols focused on food and physical activity were adhered to closely; however, protocols for handling completed forms and ensuring data security showed more variability. Quality assurance protocols are common in the clinical literature but are limited in multi-site community-based studies, especially in underserved populations. The reduction in the number of QA problems found in the second as compared to the first data collection periods for the intervention study attest to the value of this assessment. This paper can serve as a reference for similar studies wishing to implement quality assurance protocols of the data collection process to preserve data integrity and enhance the validity of study findings. NIH clinical trial #NCT01881373.

Physiological, Perceptual, and Affective Responses to Six High-Intensity Interval Training Protocols.

PubMed

Follador, Lucio; Alves, Ragami C; Ferreira, Sandro Dos S; Buzzachera, Cosme F; Andrade, Vinicius F Dos S; Garcia, Erick D S de A; Osiecki, Raul; Barbosa, Sara C; de Oliveira, Letícia M; da Silva, Sergio G

2018-04-01

This study examined the extent to which different high-intensity interval training (HIIT) and sprint interval training (SIT) protocols could influence psychophysiological responses in moderately active young men. Fourteen participants completed, in a randomized order, three cycling protocols (SIT: 4 × 30-second all-out sprints; Tabata: 7 × 20 seconds at 170% ⋮O 2max ; and HIIT: 10 × 60 seconds at 90% HR max ) and three running HIIT protocols (4 × 4 minutes at 90%-95% HR max , 5 × at v⋮O 2max , and 4 × 1,000 meters at a rating of perceived exertion (RPE) of 8, from the OMNI-Walk/Run scale). Oxygen uptake (⋮O 2 ), heart rate, and RPE were recorded during each interval. Affective responses were assessed before and after each trial. The Tabata protocol elicited the highest ⋮O 2 and RPE responses, and the least pleasant session-affect among the cycling trials. The v⋮O 2max elicited the highest ⋮O 2 and RPE responses and the lowest mean session-affect among the running trials. Findings highlight the limited application of SIT and some HIIT protocols to individuals with low fitness levels.

Adjuvant and induction chemotherapy in non-small cell lung cancer.

PubMed

Pirker, R; Malayeri, R; Huber, H

1999-01-01

About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.

System requirements for a computerised patient record information system at a busy primary health care clinic.

PubMed

Blignaut, P J; McDonald, T; Tolmie, C J

2001-05-01

A prototyping approach was used to determine the essential system requirements of a computerised patient record information system for a typical township primary health care clinic. A pilot clinic was identified and the existing manual system and business processes in this clinic was studied intensively before the first prototype was implemented. Interviews with users, incidental observations and analysis of actual data entered were used as primary techniques to refine the prototype system iteratively until a system with an acceptable data set and adequate functionalities were in place. Several non-functional and user-related requirements were also discovered during the prototyping period.

The effect of maternal methadone use on the fetal heart pattern: a computerised CTG analysis.

PubMed

Navaneethakrishnan, R; Tutty, S; Sinha, C; Lindow, S W

2006-08-01

Using a computerised analysis, the cardiotocograph (CTG) from women who use methadone (n= 25) when compared with women who do not use methadone (n= 25) showed a significant reduction in the fetal heart baseline rate, with a significant reduction in number of accelerations and episodes of high variation. The short-term variation, number of decelerations and episodes of low variation were not different between the two groups. The time taken to meet the standardised criteria was not different, and it is possible that a computer-assisted CTG analysis could be more accurate than a naked eye interpretation.

Low-cost printing of computerised tomography (CT) images where there is no dedicated CT camera.

PubMed

Tabari, Abdulkadir M

2007-01-01

Many developing countries still rely on conventional hard copy images to transfer information among physicians. We have developed a low-cost alternative method of printing computerised tomography (CT) scan images where there is no dedicated camera. A digital camera is used to photograph images from the CT scan screen monitor. The images are then transferred to a PC via a USB port, before being printed on glossy paper using an inkjet printer. The method can be applied to other imaging modalities like ultrasound and MRI and appears worthy of emulation elsewhere in the developing world where resources and technical expertise are scarce.

[Survey on computerized immunization registries in Italy].

PubMed

Alfonsi, V; D'Ancona, F; Ciofi degli Atti, M L

2008-01-01

Computerized immunization registries are essential for conducting and monitoring vaccination programs. In fact, they enable to improve vaccine offering to target population, generating needed-immunization lists and assessing levels of vaccination coverage. In 2007, a national survey on immunization registries was conducted in Italy. In February 2007, all the 21 Regional Health Authorities (RHAs) completed and returned an ad hoc questionnaire. In June 2007, RHAs were further contacted by telephone in order to verify and update the information provided in questionnaires. In 9 Italian Regions (42.8%), vaccination registries are computerized in all Local Health Units (LHUs). In five of these Regions, all LHUs use the same software, while in the remaining four Regions, different softwares are in use. In six additional Regions (28.6%), only some LHUs use computerized immunization registries (range 61.5%-95%). In the remaining 6 Regions (28.6%), which are all in Southern Italy, there are no computerised immunization registries at all. In total, computerised immunization registries cover 126/180 Italian LHUs (70%); in 76/126 (60%) of these LUHs, immunization registries are linked with population registries. This survey shows the need to improve the implementation of computerised immunization registries in Italy, especially in Southern Regions.

Computerised analysis of facial emotion expression in eating disorders.

PubMed

Leppanen, Jenni; Dapelo, Marcela Marin; Davies, Helen; Lang, Katie; Treasure, Janet; Tchanturia, Kate

2017-01-01

Problems with social-emotional processing are known to be an important contributor to the development and maintenance of eating disorders (EDs). Diminished facial communication of emotion has been frequently reported in individuals with anorexia nervosa (AN). Less is known about facial expressivity in bulimia nervosa (BN) and in people who have recovered from AN (RecAN). This study aimed to pilot the use of computerised facial expression analysis software to investigate emotion expression across the ED spectrum and recovery in a large sample of participants. 297 participants with AN, BN, RecAN, and healthy controls were recruited. Participants watched film clips designed to elicit happy or sad emotions, and facial expressions were then analysed using FaceReader. The finding mirrored those from previous work showing that healthy control and RecAN participants expressed significantly more positive emotions during the positive clip compared to the AN group. There were no differences in emotion expression during the sad film clip. These findings support the use of computerised methods to analyse emotion expression in EDs. The findings also demonstrate that reduced positive emotion expression is likely to be associated with the acute stage of AN illness, with individuals with BN showing an intermediate profile.

Exploring the impact of instructional approaches on the learning and transfer of medication dosage calculation competency.

PubMed

Glaister, Karen

2005-09-01

The ability of nurses to perform accurate drug dosage calculations has repercussions for patients' well-being. How best to assist nurses develop competency in this area is paramount. This paper presents findings of a study conducted with undergraduate nurses to determine the effect of three instructional approaches on the learning of this skill. The quasi-experimental study exposed participants to one of three instructional approaches: integrative learning, computerised learning and a combination of integrative and computerised learning. Quantitative and qualitative approaches were used to explore differences in the instructional approaches and gain further understanding of the learning process. There was no statistical difference between the three instructional approaches on knowledge acquisition and transfer measures, other than measures for procedural knowledge, which was significant (F(2,47) = 3.33 at p < .044). A least-significant difference post hoc test (alpha = 0. 10) indicated computerised learning was significantly more effective in developing procedural knowledge. The provision of instructional strategies, which facilitate development of conditional knowledge and automaticity, is necessary for competency development in dosage calculations. Furthermore, the curriculum must incorporate authentic tasks and permit time to support competency attainment.

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

PubMed

Bruce, Julie; Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-18

Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. ISRCTN 71002650; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Barriers and enablers to implementing clinical treatment protocols for fever, hyperglycaemia, and swallowing dysfunction in the Quality in Acute Stroke Care (QASC) Project--a mixed methods study.

PubMed

Dale, Simeon; Levi, Christopher; Ward, Jeanette; Grimshaw, Jeremy M; Jammali-Blasi, Asmara; D'Este, Catherine; Griffiths, Rhonda; Quinn, Clare; Evans, Malcolm; Cadilhac, Dominique; Cheung, N Wah; Middleton, Sandy

2015-02-01

The Quality in Acute Stroke Care (QASC) trial evaluated systematic implementation of clinical treatment protocols to manage fever, sugar, and swallow (FeSS protocols) in acute stroke care. This cluster-randomised controlled trial was conducted in 19 stroke units in Australia. To describe perceived barriers and enablers preimplementation to the introduction of the FeSS protocols and, postimplementation, to determine which of these barriers eventuated as actual barriers. Preimplementation: Workshops were held at the intervention stroke units (n = 10). The first workshop involved senior clinicians who identified perceived barriers and enablers to implementation of the protocols, the second workshop involved bedside clinicians. Postimplementation, an online survey with stroke champions from intervention sites was conducted. A total of 111 clinicians attended the preimplementation workshops, identifying 22 barriers covering four main themes: (a) need for new policies, (b) limited workforce (capacity), (c) lack of equipment, and (d) education and logistics of training staff. Preimplementation enablers identified were: support by clinical champions, medical staff, nursing management and allied health staff; easy adaptation of current protocols, care-plans, and local policies; and presence of specialist stroke unit staff. Postimplementation, only five of the 22 barriers identified preimplementation were reported as actual barriers to adoption of the FeSS protocols, namely, no previous use of insulin infusions; hyperglycaemic protocols could not be commenced without written orders; medical staff reluctance to use the ASSIST swallowing screening tool; poor level of engagement of medical staff; and doctors' unawareness of the trial. The process of identifying barriers and enablers preimplementation allowed staff to take ownership and to address barriers and plan for change. As only five of the 22 barriers identified preimplementation were reported to be actual barriers at completion of the trial, this suggests that barriers are often overcome whilst some are only ever perceived rather than actual barriers. © 2015 Sigma Theta Tau International.

Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.

PubMed

Yeh, Hsin-Chieh; Clark, Jeanne M; Emmons, Karen E; Moore, Reneé H; Bennett, Gary G; Warner, Erica T; Sarwer, David B; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A; Wells, Barbara; Wadden, Thomas A; Colditz, Graham A; Appel, Lawrence J

2010-08-01

The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.

Head Tilt Posturography to Enhance Balance Control Assessment for Astronauts: A Case Study

NASA Technical Reports Server (NTRS)

Hwang, E. Y.; Paloski, W. H.

2006-01-01

For many years, we have used a standard clinical computerized dynamic posturography (CDP) protocol to assess recovery of integrated sensory-motor function in astronauts returning from space flight. The most reliable indications of postflight crew performance capabilities have been obtained from the sensory organization tests (SOTs) within the CDP protocol, particularly SOTs 5 (eyes closed, surface support sway referenced) and 6 (eyes open, surface support and visual surround sway referenced), which are sensitive to changes in availability and/or utilization of vestibular cues. We have observed, however, that some astronauts exhibiting visible signs of incomplete sensory-motor recovery are able to score within clinical norms on standard SOTs 5 and 6 trials, perhaps as a result of cognitive strategies driven by their naturally competitive natures. To improve the sensitivity of the CDP protocol for assessing recovery of integrated sensory-motor function and fitness to return to duties and/or activities of daily living, we have introduced pitch plane head tilt SOT trials to our protocol. In a preliminary study of 5 short duration (11day missions) astronauts, we showed that they were unable to maintain balance on landing day when performing dynamic head tilt trials, despite scoring within the clinically normal range on the standard SOT trials. The present case report illustrates the advantages of including head tilt trials for assessing sensory-motor recovery in long duration crewmembers.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery

PubMed Central

Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-01-01

Introduction Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions—physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. Methods and analysis This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. Ethics and dissemination This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. Trial registration number NCT02921932 (ClinicalTrials.gov) PMID:28778994

Randomized trial for answers to clinical questions: evaluating a pre-appraised versus a MEDLINE search protocol.

PubMed

Patel, Manesh R; Schardt, Connie M; Sanders, Linda L; Keitz, Sheri A

2006-10-01

The paper compares the speed, validity, and applicability of two different protocols for searching the primary medical literature. A randomized trial involving medicine residents was performed. An inpatient general medicine rotation was used. Thirty-two internal medicine residents were block randomized into four groups of eight. Success rate of each search protocol was measured by perceived search time, number of questions answered, and proportion of articles that were applicable and valid. Residents randomized to the MEDLINE-first (protocol A) group searched 120 questions, and residents randomized to the MEDLINE-last (protocol B) searched 133 questions. In protocol A, 104 answers (86.7%) and, in protocol B, 117 answers (88%) were found to clinical questions. In protocol A, residents reported that 26 (25.2%) of the answers were obtained quickly or rated as "fast" (<5 minutes) as opposed to 55 (51.9%) in protocol B, (P = 0.0004). A subset of questions and articles (n = 79) were reviewed by faculty who found that both protocols identified similar numbers of answer articles that addressed the questions and were felt to be valid using critical appraisal criteria. For resident-generated clinical questions, both protocols produced a similarly high percentage of applicable and valid articles. The MEDLINE-last search protocol was perceived to be faster. However, in the MEDLINE-last protocol, a significant portion of questions (23%) still required searching MEDLINE to find an answer.

THE RELIABILITY OF HAND-WRITTEN AND COMPUTERISED RECORDS OF BIRTH DATA COLLECTED AT BARAGWANATH HOSPITAL IN SOWETO

PubMed Central

Ellison, GTH; Richter, LM; de Wet, T; Harris, HE; Griesel, RD; McIntyre, JA

2007-01-01

This study examined the reliability of hand-written and computerised records of birth data collected during the Birth to Ten study at Baragwanath Hospital in Soweto. The reliability of record-keeping in hand-written obstetric and neonatal files was assessed by comparing duplicate records of six different variables abstracted from six different sections in these files. The reliability of computerised record-keeping was assessed by comparing the original hand-written record of each variable with records contained in the hospital’s computerised database. These data sets displayed similar levels of reliability which suggests that similar errors occurred when data were transcribed from one section of the files to the next, and from these files to the computerised database. In both sets of records reliability was highest for the categorical variable infant sex, and for those continuous variables (such as maternal age and gravidity) recorded with unambiguous units. Reliability was lower for continuous variables that could be recorded with different levels of precision (such as birth weight), those that were occasionally measured more than once, and those that could be measured using more than one measurement technique (such as gestational age). Reducing the number of times records are transcribed, categorising continuous variables, and standardising the techniques used for measuring and recording variables would improve the reliability of both hand-written and computerised data sets. OPSOMMING In hierdie studie is die betroubaarheid van handgeskrewe en gerekenariseerde rekords van ge boortedata ondersoek, wat versamel is gedurende die ‘Birth to Ten’ -studie aan die Baragwanath hospitaal in Soweto. Die betroubaarheid van handgeskrewe verloskundige en pasgeboortelike rekords is beoordeel deur duplikaatrekords op ses verskillende verander likes te vergelyk, wat onttrek is uit ses verskillende dele van die betrokke lêers. Die gerekenariseerde rekords se betroubaarheid is beoordeel deur die oorspronklike geskrewe rekord van elke veranderlike te vergelyk met rekords wat beskikbaar is in die hospitaal se gerekenariseerde databasis Hierdie datastelle her vergelykbare vlakke van betroubaarheid getoon, waaruit afgelei kan word dat soortgelyke foute voorkom warmeer data oorgeplaas word vaneen deeivan ’n lêer na ’n ander, en vanaf die lêer na die gerekenariseerde databasis. In albei stelle rekords was die betroubaarheid die hoogste vir die kategoriese veranderlike suigeling se geslag, en vir daardie kontinue veranderlikes (soos moeder se ouderdom en gravida) wat in terme van ondubbelsinmge eenhede gekodeer kan word. Kontinue veranderlikes wat op wisselende vlakke van akkuratheid gemeet word (soos gewig met geboorte), veranderlikes wat soms meer as een keer gemeet is, en veranderlikes wat voigens meer as een metingstegniek bepaal is (soos draagtydsouderdom), was minder betroubaar Deur die aantal kere wat rekords oorgeskryf moet word te verminder, kontinue veranderlikes tat kategoriese veranderlikes te wysig. en tegnieke vir meting en aantekening van veranderlikes te standardiseer, kan die betroubaarheid van sowel handgeskrewe as gerekenariseerde datastelle verbeter word. PMID:9287552

Activity Increase Despite Arthritis (AIDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946].

PubMed

Williams, Nefyn H; Amoakwa, Elvis; Burton, Kim; Hendry, Maggie; Belcher, John; Lewis, Ruth; Hood, Kerenza; Jones, Jeremy; Bennett, Paul; Edwards, Rhiannon T; Neal, Richard D; Andrew, Glynne; Wilkinson, Clare

2009-09-04

Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity. This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months. We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial. Current Controlled Trials ISRCTN24554946.

Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

Cancer.gov

A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

PubMed

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D; Wildey, Carol; Versace, Vincent L; Hagger, Virginia; Asproloupos, Dino; O'Reilly, Sharleen L; Phillips, Paddy A; Ackland, Michael; Skinner, Timothy; Oats, Jeremy; Carter, Rob; Best, James D; Dunbar, James A

2014-06-30

The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

Effectiveness of conventional versus virtual reality based vestibular rehabilitation in the treatment of dizziness, gait and balance impairment in adults with unilateral peripheral vestibular loss: a randomised controlled trial.

PubMed

Meldrum, Dara; Herdman, Susan; Moloney, Roisin; Murray, Deirdre; Duffy, Douglas; Malone, Kareena; French, Helen; Hone, Stephen; Conroy, Ronan; McConn-Walsh, Rory

2012-03-26

Unilateral peripheral vestibular loss results in gait and balance impairment, dizziness and oscillopsia. Vestibular rehabilitation benefits patients but optimal treatment remains unknown. Virtual reality is an emerging tool in rehabilitation and provides opportunities to improve both outcomes and patient satisfaction with treatment. The Nintendo Wii Fit Plus® (NWFP) is a low cost virtual reality system that challenges balance and provides visual and auditory feedback. It may augment the motor learning that is required to improve balance and gait, but no trials to date have investigated efficacy. In a single (assessor) blind, two centre randomised controlled superiority trial, 80 patients with unilateral peripheral vestibular loss will be randomised to either conventional or virtual reality based (NWFP) vestibular rehabilitation for 6 weeks. The primary outcome measure is gait speed (measured with three dimensional gait analysis). Secondary outcomes include computerised posturography, dynamic visual acuity, and validated questionnaires on dizziness, confidence and anxiety/depression. Outcome will be assessed post treatment (8 weeks) and at 6 months. Advances in the gaming industry have allowed mass production of highly sophisticated low cost virtual reality systems that incorporate technology previously not accessible to most therapists and patients. Importantly, they are not confined to rehabilitation departments, can be used at home and provide an accurate record of adherence to exercise. The benefits of providing augmented feedback, increasing intensity of exercise and accurately measuring adherence may improve conventional vestibular rehabilitation but efficacy must first be demonstrated. Clinical trials.gov identifier: NCT01442623.

To eat or not to eat. The effects of expectancy on reactivity to food cues.

PubMed

Hardman, Charlotte A; Scott, Jade; Field, Matt; Jones, Andrew

2014-05-01

Cue reactivity may be determined by the ability of cues to evoke expectations that a reward will be imminently received. To test this possibility, the current study examined the effects of manipulating expectations about the receipt of food (pizza) on self-reported and physiological responses to pizza cues, and attentional bias to pizza pictures. It was predicted that expecting to eat pizza would increase salivation, self-reported measures of motivation and attentional bias to pizza cues relative to conditions where there was no eating expectancy. In a within-subjects counterbalanced design, 42 hungry participants completed two pizza-cue exposures in a single experimental session during which their expectation of consuming the pizza was manipulated (i.e., expectancy of eating imminently vs. no eating expectancy). They also completed a computerised attentional bias task during which the probability of receiving pizza (0%, 50% or 100%) was manipulated on a trial-by-trial basis. Participants showed reliable increases in hunger and salivation in response to the pizza cues, as well as a bias in attentional maintenance on pizza pictures. However, these responses were not influenced by eating expectancy. Contrastingly, expectancy did influence early attentional processing (initial orientation of attention) in that participants directed their first gaze towards pizza pictures more often on 100% and 50% probability trials relative to 0% trials. Overall, our findings indicate that exposure to food cues triggers appetitive responses regardless of explicit expectancy information. Methodological features of the study that may account for these findings are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

How blockchain-timestamped protocols could improve the trustworthiness of medical science

PubMed Central

Irving, Greg; Holden, John

2017-01-01

Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Methods for using blockchain to provide proof of pre-specified endpoints in clinical trial protocols were first reported by Carlisle. We wished to empirically test such an approach using a clinical trial protocol where outcome switching has previously been reported. Here we confirm the use of blockchain as a low cost, independently verifiable method to audit and confirm the reliability of scientific studies. PMID:27239273

How blockchain-timestamped protocols could improve the trustworthiness of medical science.

PubMed

Irving, Greg; Holden, John

2016-01-01

Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Methods for using blockchain to provide proof of pre-specified endpoints in clinical trial protocols were first reported by Carlisle. We wished to empirically test such an approach using a clinical trial protocol where outcome switching has previously been reported. Here we confirm the use of blockchain as a low cost, independently verifiable method to audit and confirm the reliability of scientific studies.

Informed Consent to Study Purpose in Randomized Clinical Trials of Antibiotics, 1991 Through 2011.

PubMed

Doshi, Peter; Hur, Peter; Jones, Mark; Albarmawi, Husam; Jefferson, Tom; Morgan, Daniel J; Spears, Patricia A; Powers, John H

2017-10-01

Potential research participants may assume that randomized trials comparing new interventions with older interventions always hypothesize greater efficacy for the new intervention, as in superiority trials. However, antibiotic trials frequently use "noninferiority" hypotheses allowing a degree of inferior efficacy deemed "clinically acceptable" compared with an older effective drug, in exchange for nonefficacy benefits (eg, decreased adverse effects). Considering these different benefit-harm trade-offs, proper informed consent necessitates supplying different information on the purposes of superiority and noninferiority trials. To determine the degree to which the study purpose is explained to potential participants in randomized clinical trials of antibiotics and the degree to which study protocols justify their selection of noninferiority hypotheses and amount of "clinically acceptable" inferiority. Cross-sectional analysis of study protocols, statistical analysis plans (SAPs), and informed consent forms (ICFs) from clinical study reports submitted to the European Medicines Agency. The ICFs were read by both methodologists and patient investigators. Protocols and SAPs were used as the reference standard to determine prespecified primary hypothesis and record rationale for selection of noninferiority hypotheses and noninferiority margins. This information was cross-referenced against ICFs to determine whether ICFs explained the study purpose. We obtained trial documents from 78 randomized trials with prespecified efficacy hypotheses (6 superiority, 72 noninferiority) for 17 antibiotics conducted between 1991 and 2011 that enrolled 39 407 patients. Fifty were included in the ICF analysis. All ICFs contained sections describing study purpose; however, none consistently conveyed study hypothesis to both methodologists and patient investigators. Methodologists found that 1 of 50 conveyed a study purpose. Patient investigators found that 11 of 50 conveyed a study purpose, 7 accurately and 4 inaccurately compared with the reference standard. Seventy-one of 72 noninferiority trial protocols or SAPs provided no rationale for selection of noninferiority hypothesis. None provided a clinical rationale for the chosen amount of decreased efficacy. Patients were not accurately informed of study purpose, which raises questions regarding the ethics of informed consent in antibiotic trials. Noninferiority and superiority trials entail different benefit-harm trade-offs that must be conveyed for ethical informed consent.

Time to publication for publicly funded clinical trials in Australia: an observational study.

PubMed

Strand, Linn Beate; Clarke, Philip; Graves, Nicholas; Barnett, Adrian G

2017-03-22

To examine the length of time between receiving funding and publishing the protocol and main paper for randomised controlled trials. An observational study using survival analysis. Publicly funded health and medical research in Australia. Randomised controlled trials funded by the National Health and Medical Research Council of Australia between 2008 and 2010. Time from funding to the protocol paper and main results paper. Multiple variable survival models examining whether study characteristics predicted publication times. We found 77 studies with a total funding of $A59 million. The median time to publication of the protocol paper was 6.4 years after funding (95% CI 4.1 to 8.1). The proportion with a published protocol paper 8 years after funding was 0.61 (95% CI 0.48 to 0.74). The median time to publication of the main results paper was 7.1 years after funding (95% CI 6.3 to 7.6). The proportion with a published main results paper 8 years after funding was 0.72 (95% CI 0.56 to 0.87). The HRs for how study characteristics might influence timing were generally close to one with narrow CIs, the notable exception was that a longer study length lengthened the time to the main paper (HR=0.62 per extra study year, 95% CI 0.43 to 0.89). Despite the widespread registration of clinical trials, there remain serious concerns of trial results not being published or being published with a long delay. We have found that these same concerns apply to protocol papers, which should be publishable soon after funding. Funding agencies could set a target of publishing the protocol paper within 18 months of funding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The second Symptom Management Research Trial in Oncology (SMaRT Oncology-2): a randomised trial to determine the effectiveness and cost-effectiveness of adding a complex intervention for major depressive disorder to usual care for cancer patients.

PubMed

Walker, Jane; Cassidy, Jim; Sharpe, Michael

2009-03-30

Depression Care for People with Cancer is a complex intervention delivered by specially trained cancer nurses, under the supervision of a psychiatrist. It is given as a supplement to the usual care for depression, which patients receive from their general practitioner and cancer service. In a 'proof of concept' trial (Symptom Management Research Trials in Oncology-1) Depression Care for People with Cancer improved depression more than usual care alone. The second Symptom Management Research Trial in Oncology (SMaRT Oncology-2 Trial) will test its effectiveness and cost-effectiveness in a 'real world' setting. A two arm parallel group multi-centre randomised controlled trial. TRIAL PROCEDURES: 500 patients will be recruited through established systematic Symptom Monitoring Services, which screen patients for depression. Patients will have: a diagnosis of cancer (of various types); an estimated life expectancy of twelve months or more and a diagnosis of Major Depressive Disorder. Patients will be randomised to usual care or usual care plus Depression Care for People with Cancer. Randomisation will be carried out by telephoning a secure computerised central randomisation system or by using a secure web interface. The primary outcome measure is 'treatment response' measured at 24 week outcome data collection. 'Treatment response' will be defined as a reduction of 50% or more in the patient's baseline depression score, measured using the 20-item Symptom Checklist (SCL-20D). Secondary outcomes include remission of major depressive disorder, depression severity and patients' self-rated improvement of depression. Current controlled trials ISRCTN40568538 TRIAL HYPOTHESES: (1) Depression Care for People with Cancer as a supplement to usual care will be more effective than usual care alone in achieving a 50% reduction in baseline SCL-20D score at 24 weeks. (2) Depression Care for People with Cancer as a supplement to usual care will cost more than usual care alone but will be more cost effective in achieving improvements in patients' depression and quality of life.

A Method of Managing Severe Traumatic Brain Injury in the Absence of Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol.

PubMed

Chesnut, Randall M; Temkin, Nancy; Dikmen, Sureyya; Rondina, Carlos; Videtta, Walter; Petroni, Gustavo; Lujan, Silvia; Alanis, Victor; Falcao, Antonio; de la Fuenta, Gustavo; Gonzalez, Luis; Jibaja, Manuel; Lavarden, Arturo; Sandi, Freddy; Mérida, Roberto; Romero, Ricardo; Pridgeon, Jim; Barber, Jason; Machamer, Joan; Chaddock, Kelley

2018-01-01

The imaging and clinical examination (ICE) algorithm used in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial is the only prospectively investigated clinical protocol for traumatic brain injury management without intracranial pressure (ICP) monitoring. As the default literature standard, it warrants careful evaluation. We present the ICE protocol in detail and analyze the demographics, outcome, treatment intensity, frequency of intervention usage, and related adverse events in the ICE-protocol cohort. The 167 ICE protocol patients were young (median 29 years) with a median Glasgow Coma Scale motor score of 4 but with anisocoria or abnormal pupillary reactivity in 40%. This protocol produced outcomes not significantly different from those randomized to the monitor-based protocol (favorable 6-month extended Glasgow Outcome Score in 39%; 41% mortality rate). Agents commonly employed to treat suspected intracranial hypertension included low-/moderate-dose hypertonic saline (72%) and mannitol (57%), mild hyperventilation (adjusted partial pressure of carbon dioxide 30-35 mm Hg in 73%), and pressors to maintain cerebral perfusion (62%). High-dose hyperosmotics or barbiturates were uncommonly used. Adverse event incidence was low and comparable to the BEST TRIP monitored group. Although this protocol should produce similar/acceptable results under circumstances comparable to those in the trial, influences such as longer pre-hospital times and non-specialist transport personnel, plus an intensive care unit model of aggressive physician-intensive care by small groups of neurotrauma-focused intensivists, which differs from most high-resource models, support caution in expecting the same results in dissimilar settings. Finally, this protocol's ICP-titration approach to suspected intracranial hypertension (vs. crisis management for monitored ICP) warrants further study.

Participation in Pediatric Oncology Research Protocols: Racial/ethnic, Language and Age-based Disparities

PubMed Central

Aristizabal, Paula; Singer, Jenelle; Cooper, Renee; Wells, Kristen J.; Nodora, Jesse; Milburn, Mehrzad; Gahagan, Sheila; Schiff, Deborah E.; Martinez, Maria Elena

2015-01-01

Background Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio-demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type and insurance status. Procedure Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children’s Hospital. Results Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyses revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; p=0.021) and among children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; p=0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; p<0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately. Conclusions There was significant underrepresentation in protocol participation for Hispanics, children of Spanish-speaking parents, and patients ages 15–21. Research is urgently needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. PMID:25755225

Bridging the gap in complementary and alternative medicine research: manualization as a means of promoting standardization and flexibility of treatment in clinical trials of acupuncture.

PubMed

Schnyer, Rosa N; Allen, John J B

2002-10-01

An important methodological challenge encountered in acupuncture clinical research involves the design of treatment protocols that help ensure standardization and replicability while allowing for the necessary flexibility to tailor treatments to each individual. Manualization of protocols used in clinical trials of acupuncture and other traditionally-based complementary and alternative medicine (CAM) systems facilitates the systematic delivery of replicable and standardized, yet individually-tailored treatments. To facilitate high-quality CAM acupuncture research by outlining a method for the systematic design and implementation of protocols used in CAM clinical trials based on the concept of treatment manualization. A series of treatment manuals was developed to systematically articulate the Chinese medical theoretical and clinical framework for a given Western-defined illness, to increase the quality and consistency of treatment, and to standardize the technical aspects of the protocol. In all, three manuals were developed for National Institutes of Health (NIH)-funded clinical trials of acupuncture for depression, spasticity in cerebral palsy, and repetitive stress injury. In Part I, the rationale underlying these manuals and the challenges encountered in creating them are discussed, and qualitative assessments of their utility are provided. In Part II, a methodology to develop treatment manuals for use in clinical trials is detailed, and examples are given. A treatment manual provides a precise way to train and supervise practitioners, enable evaluation of conformity and competence, facilitate the training process, and increase the ability to identify the active therapeutic ingredients in clinical trials of acupuncture.

IL-6, Antioxidant Capacity and Muscle Damage Markers Following High-Intensity Interval Training Protocols.

PubMed

Cipryan, Lukas

2017-02-01

The aim of this study was to investigate changes of interleukin-6 (IL-6), total antioxidant capacity (TAC) and muscle damage markers (creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH)) in response to three different high-intensity interval training (HIIT) protocols of identical external work. Twelve moderately-trained males participated in the three HIIT trials which consisted of a warm-up, followed by 12 min of 15 s, 30 s or 60 s HIIT sequences with the work/rest ratio 1. The biochemical markers of inflammation, oxidative stress and muscle damage were analysed POST, 3 h and 24 h after the exercise. All HIIT protocols caused an immediate increase in IL-6, TAC, CK, myoglobin and LDH. The most pronounced between-trials differences were found for the POST-exercise changes in IL-6 (Effect size ± 90% confidence interval: 1.51 ± 0.63, 0.84 ± 0.34 and 1.80 ± 0.60 for the 15s/15s, 30s/30s and 60s/60s protocol, respectively) and myoglobin (1.11 ± 0.29, 0.45 ± 0.48 and 1.09 ± 0.22 for the 15s/15s, 30s/30s and 60s/60s protocol, respectively). There were no substantial between-trial differences in other biochemical variables. In conclusion, the 15s/15s and 60s/60s protocols might be preferred to the 30s/30s protocols in order to maximize the training stimulus.

Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

PubMed Central

Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

2010-01-01

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

How to customize a bona fide psychotherapy for generalized anxiety disorder? A two-arms, patient blinded, ABAB crossed-therapist randomized clinical implementation trial design [IMPLEMENT 2.0].

PubMed

Flückiger, Christoph; Wolfer, Christine; Held, Judith; Hilpert, Peter; Rubel, Julian; Allemand, Mathias; Zinbarg, Richard E; Vîslă, Andreea

2018-04-03

Bona fide psychotherapy approaches are effective treatments for generalized anxiety disorder (GAD) compared to no-treatment conditions. Treatment manuals and protocols allow a relatively high degree of freedom for the way therapists implement these overall treatment packages and there is a systematic lack of knowledge on how therapists should customize these treatments. The present study experimentally examines two implementation strategies of customizing a bona fide psychotherapy approach based on a 16 session time-limited cognitive-behavioral therapy (CBT) protocol and their relation to the post-session and ultimate treatment outcomes. This trial contrasts two different implementation strategies of how to customize the in-session structure of a manual-based CBT-protocol for GAD. The patients will be randomly assigned to two implementation conditions: (1) a systematic focus on subtle changes lasting from 7 to 20 min at the check-in phase of every psychotherapy session and (2) a state-of-the-art (SOTA) check-in phase lasting several minutes mainly focused on the session goals. Potential therapist effects will be examined based on an ABAB crossed-therapist design. Treatment outcomes will be assessed at the following times: post-session outcomes, treatment outcome at post assessment and 6- as well as 12-month follow-up. The proposed randomized clinical implementation trial addresses the clinically relevant question of how to customize a bona fide psychotherapy protocol experimentally contrasting two implementation strategies. Through the development and testing of the proposed implementation design, this trial has the potential to inform therapists about efficacious implementation strategies of how to customize a manual-based treatment protocol in respect to the timing of the in-session structure. This trial was registered at ClinicalTrials.gov ( NCT03079336 ) at March 14, 2017.

The implementation and adherence to evidence-based protocols for psychotherapy for depression: the perspective of therapists in Dutch specialized mental healthcare.

PubMed

Bruijniks, Sanne J E; Franx, Gerdien; Huibers, Marcus J H

2018-06-14

Although psychotherapy is an effective treatment for depression, a large number of patients still do not receive care according to the protocols that are used in clinical trials. Instead, patients often receive a modified version of the original intervention. It is not clear how and when treatment protocols are used or modified in the Dutch specialized mental health care and whether these changes lead to suboptimal adherence to treatment protocols. In the context of an ongoing multicenter trial that investigates whether twice-weekly sessions of protocolized interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) for depression lead to better treatment outcomes compared to once-weekly sessions, two focus groups using semi-structured interviews were organized. Aims were to increase insight in the adherence to and modifications of CBT and IPT protocols in the Dutch specialized mental health care for depression. Participants were fifteen therapists from seven mental health locations part of five mental health organizations. Verbatim transcripts were coded and analyzed using qualitative software. Three themes emerged: modification as the common practice, professional and patient factors influencing the adherence to protocols and organizational boundaries and flexibility. Treatment modification appeared to happen on a frequent basis, even in the context of a trial. Definitions of treatment modifications were multiple and varied from using intuition to flexible use of the same protocol. Therapist training and supervision, the years of work experience and individual characteristics of the therapist and the patient were mentioned to influence the adherence to protocols. Modifications of the therapists depended very much on the culture within the mental health locations, who differed in terms of the flexibility offered to therapists to choose and modify treatment protocols. Not all treatment modifications were in line with existing evidence or guidelines. Regular supervision, team meetings and a shared vision were identified as crucial factors to increase adherence to treatment protocols, whereas additional organizational factors, among which a change of mindset, may facilitate adequate implementation.

Improving delirium care in the intensive care unit: The design of a pragmatic study

PubMed Central

2011-01-01

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608 PMID:21645330

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

Dry needling in a manual physiotherapy and therapeutic exercise protocol for patients with chronic mechanical shoulder pain of unspecific origin: a protocol for a randomized control trial.

PubMed

Tejera-Falcón, Emma; Toledo-Martel, Nuria Del Carmen; Sosa-Medina, Francisco Manuel; Santana-González, Fátima; Quintana-de la Fe, Miriam Del Pino; Gallego-Izquierdo, Tomás; Pecos-Martín, Daniel

2017-09-18

Shoulder pain of musculoskeletal origin is the main cause of upper limb pain of non-traumatic origin. Despite being one of the most common reasons for consultation, there is no established protocol for treatment due to the complexity of its etiology. However, it has been shown that the presence of myofascial trigger points on the shoulder muscles is a common condition associated with patients suffering from shoulder pain. This protocol has been created which describes the design of a randomized controlled trial to evaluate the effectiveness of the inclusion of dry needling (DN) within a protocol of manual physiotherapy and therapeutic exercise in the treatment of chronic shoulder pain of unspecific origin. Thirty-six participants aged 18-65 years will be recruited having mechanical chronic shoulder pain on unspecific origin and meeting the inclusion criteria. These will be randomized to one of two interventions, (i) DN, manual physiotherapy and therapeutic exercise or (ii) sham DN, manual physiotherapy and therapeutic exercise. The protocol will cover 6 weeks of treatment, with a 6-month follow-up. Our main outcome measure will be the Visual Analogue Scale for pain. This is the first study to combine the use of DN, manual physiotherapy and an exercise program with a 6-month follow-up, thus becoming a new contribution to the treatment of chronic shoulder pain, while new lines of research may be established to help determine the effects of DN on chronic shoulder pain and the frequency and proper dosage. International Standard Randomized Controlled Trial Number Register: ISRCTN30604244 ( http://www.controlled-trials.com ) 29 June 2016.

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Neurofeedback, sham neurofeedback, and cognitive-behavioural group therapy in adults with attention-deficit hyperactivity disorder: a triple-blind, randomised, controlled trial.

PubMed

Schönenberg, Michael; Wiedemann, Eva; Schneidt, Alexander; Scheeff, Jonathan; Logemann, Alexander; Keune, Philipp M; Hautzinger, Martin

2017-09-01

Many studies suggest that electroencephalographic (EEG) neurofeedback might be beneficial in the treatment of attention-deficit hyperactivity disorder (ADHD). However, numbers of well controlled studies are low and neurofeedback techniques are regarded as highly controversial. The present trial examined the efficacy (compared with sham neurofeedback) and efficiency (compared with meta-cognitive therapy) of a standard EEG neurofeedback protocol in adults with ADHD. We did a concurrent, triple-blind, randomised, controlled trial using authorised deception in adults with ADHD from one centre (University of Tübingen) in Tübingen, Germany. Participants were eligible if they fulfilled the DSM-IV-TR criteria for ADHD, were aged between 18 years and 60 years, and had no or stable use of medication for at least 2 months with no intention to change. We excluded participants who had comorbid schizophrenia or schizoaffective disorder, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury; substance abuse or dependence; or current or planned other psychological treatment. Those eligible were randomly assigned to three groups: a neurofeedback group which received 30 verum θ-to-β neurofeedback sessions over 15 weeks, a sham neurofeedback group which received 15 sham followed by 15 verum θ-to-β neurofeedback sessions over 15 weeks, or a meta-cognitive group therapy group which received 12 sessions over 12 weeks. Participants were assigned equally to one of the three interventions through a computerised minimisation randomisation procedure stratified by sex, age, and baseline symptom severity of ADHD. Participants were masked as to whether they were receiving neurofeedback or sham neurofeedback, but those receiving meta-cognitive therapy were aware of their treatment. Clinical assessors (ie, those assessing outcomes) and research staff who did the neurofeedback training were masked to participants' randomisation status only for neurofeedback and sham neurofeedback. The primary outcome was symptom score on the Conners' adult ADHD rating scale, assessed before treatment, at midtreatment (after 8 weeks), after treatment (after 16 weeks), and 6 months later. All individuals with at least one observation after randomisation were included in the analyses. This trial is registered with ClinicalTrials.gov, number NCT01883765. Between Feb 1, 2013, and Dec 1, 2015, 761 people were assessed for eligibility. 656 (86%) were excluded and 118 (15%) were eligible for participation in this study. Eligible participants were randomly assigned to neurofeedback (38 [32%]), sham neurofeedback (39 [33%]), or meta-cognitive therapy (41 [35%]). 37 (97%) individuals for neurofeedback, 38 (97%) for sham neurofeedback, and 38 (93%) for meta-cognitive therapy were included in analyses. Self-reported ADHD symptoms decreased substantially for all treatment groups (B=-2·58 [95% CI -3·48 to -1·68]; p<0·0001) between pretreatment and the end of 6 month follow-up, independent of treatment condition (neurofeedback vs sham neurofeedback B=-0·89 [95% CI -2·14 to 0·37], p=0·168; neurofeedback vs meta-cognitive therapy -0·30 [-1·55 to 0·95], p=0·639). No treatment-related or trial-related serious adverse events were reported. Our findings suggest that neurofeedback training is not superior to a sham condition or group psychotherapy. All three treatments were equivalently effective in reducing ADHD symptoms. This first randomised, sham-controlled trial did not show any specific effects of neurofeedback on ADHD symptoms in adults. German Research Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cauda equina syndrome complicating ankylosing spondylitis: use of electromyography and computerised tomography in diagnosis.

PubMed

Young, A; Dixon, A; Getty, J; Renton, P; Vacher, H

1981-06-01

A case of the cauda equina syndrome complicating ankylosing spondylitis (AS) is described. An unusual feature of this case was the relapsing and remitting nature of the condition, but there is sufficient evidence to explain the clinical picture on the basis of a recurrent intraspinal inflammatory process. The clinical and radiological features are similar to those of a further 28 reported in the literature. An electromyogram (EMG) proved important in defining the extent of neurological involvement. Computerised tomography (CT) showed marked laminar erosion and no bony exit foramen encroachment. We believe that the clinical diagnosis of this condition can be adequately confirmed with plain radiology, EMG, and CT scan.

Developing the Coach Analysis and Intervention System (CAIS): establishing validity and reliability of a computerised systematic observation instrument.

PubMed

Cushion, Christopher; Harvey, Stephen; Muir, Bob; Nelson, Lee

2012-01-01

We outline the evolution of a computerised systematic observation tool and describe the process for establishing the validity and reliability of this new instrument. The Coach Analysis and Interventions System (CAIS) has 23 primary behaviours related to physical behaviour, feedback/reinforcement, instruction, verbal/non-verbal, questioning and management. The instrument also analyses secondary coach behaviour related to performance states, recipient, timing, content and questioning/silence. The CAIS is a multi-dimensional and multi-level mechanism able to provide detailed and contextualised data about specific coaching behaviours occurring in complex and nuanced coaching interventions and environments that can be applied to both practice sessions and competition.

Assessing and Managing Risk with Suicidal Individuals

ERIC Educational Resources Information Center

Linehan, Marsh M.; Comtois, Katherine A.; Ward-Ciesielski, Erin F.

2012-01-01

The University of Washington Risk Assessment Protocol (UWRAP) and Risk Assessment and Management Protocol (UWRAMP) have been used in numerous clinical trials treating high-risk suicidal individuals over several years. These protocols structure assessors and treatment providers to provide a thorough suicide risk assessment, review standards of care…

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

PubMed Central

Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

2017-01-01

Introduction Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. Methods and analysis The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. Ethics and dissemination This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11–1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty. Trial registration number ClinicalTrials.gov (NCT02768025); pre-results. PMID:28576892

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: Is Cognitive Measurement State-of-the-Art?

PubMed

Elias, Merrill F; Torres, Rachael V; Davey, Adam

2018-05-07

Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.

Strengthening of the Hip and Core Versus Knee Muscles for the Treatment of Patellofemoral Pain: A Multicenter Randomized Controlled Trial

PubMed Central

Ferber, Reed; Bolgla, Lori; Earl-Boehm, Jennifer E.; Emery, Carolyn; Hamstra-Wright, Karrie

2015-01-01

Context: Patellofemoral pain (PFP) is the most common injury in running and jumping athletes. Randomized controlled trials suggest that incorporating hip and core strengthening (HIP) with knee-focused rehabilitation (KNEE) improves PFP outcomes. However, no randomized controlled trials have, to our knowledge, directly compared HIP and KNEE programs. Objective: To compare PFP pain, function, hip- and knee-muscle strength, and core endurance between KNEE and HIP protocols after 6 weeks of rehabilitation. We hypothesized greater improvements in (1) pain and function, (2) hip strength and core endurance for patients with PFP involved in the HIP protocol, and (3) knee strength for patients involved in the KNEE protocol. Design: Randomized controlled clinical trial. Setting: Four clinical research laboratories in Calgary, Alberta; Chicago, Illinois; Milwaukee, Wisconsin; and Augusta, Georgia. Patients or Other Participants: Of 721 patients with PFP screened, 199 (27.6%) met the inclusion criteria (66 men [31.2%], 133 women [66.8%], age = 29.0 ± 7.1 years, height = 170.4 ± 9.4 cm, weight = 67.6 ± 13.5 kg). Intervention(s): Patients with PFP were randomly assigned to a 6-week KNEE or HIP protocol. Main Outcome Measure(s): Primary variables were self-reported visual analog scale and Anterior Knee Pain Scale measures, which were conducted weekly. Secondary variables were muscle strength and core endurance measured at baseline and at 6 weeks. Results: Compared with baseline, both the visual analog scale and the Anterior Knee Pain Scale improved for patients with PFP in both the HIP and KNEE protocols (P < .001), but the visual analog scale scores for those in the HIP protocol were reduced 1 week earlier than in the KNEE group. Both groups increased in strength (P < .001), but those in the HIP protocol gained more in hip-abductor (P = .01) and -extensor (P = .01) strength and posterior core endurance (P = .05) compared with the KNEE group. Conclusions: Both the HIP and KNEE rehabilitation protocols produced improvements in PFP, function, and strength over 6 weeks. Although outcomes were similar, the HIP protocol resulted in earlier resolution of pain and greater overall gains in strength compared with the KNEE protocol. PMID:25365133

Establishing an effective TMS protocol for craving in substance addiction: Is it possible?

PubMed

Enokibara, Mailu; Trevizol, Alisson; Shiozawa, Pedro; Cordeiro, Quirino

2016-01-01

Repetitive transcranial magnetic stimulation (TMS) is a non-invasive tool with known therapeutic efficacy in various neuropsychiatric disorders, such as depression, schizophrenia, mania, and anxiety disorders. We hereby, briefly present a brief review and meta-analysis on the use of TMS for craving in substance addiction. We present our brief review and meta-analysis following the recommendations of the Cochrane group. A total of eight randomized controlled trials fulfilled eligibility criteria and were selected. A total of 199 patients were studied. We found active stimulation to be superior than sham protocols only for trials focused on right DLPFC (with Hedge's g = 1.48; ES (95%CI: 0.126-2.834), p = 0.032. Main meta-analysis limitations include small number of studies, high heterogeneity among studies, and high publication bias. However challenging, our exploratory analysis underscored the amelioration of craving in substance addiction for trials using high frequency TMS protocols over the right DLPFC. We hereby, propose the use of this particular TMS protocol as a promising tool in clinical research. © American Academy of Addiction Psychiatry.

Study protocol of a randomized controlled trial comparing integrative body-mind-spirit intervention and cognitive behavioral therapy in fostering quality of life of patients with lung cancer and their family caregivers.

PubMed

Lau, Bobo Hi-Po; Chow, Amy Y M; Wong, Daniel F K; Chan, Jessie S M; Chan, Celia H Y; Ho, Rainbow T H; So, Tsz-Him; Lam, Tai-Chung; Lee, Victor Ho-Fun; Lee, Anne W M; Chow, Sau Fong; Chan, Cecilia L W

2018-01-01

Compared to cancers at other sites, lung cancer often results in greater psychosocial distress to both the patients and their caregivers, due to the poor prognosis and survival rate, as well as the heavy symptom burden. In recent years, making protocols of proposed or on-going studies publicly available via clinical trial registries and/or peer-reviewed journals has benefited health sciences with timely communication of the latest research trends and improved transparency in reporting. However, such practice is yet to be a common sight in evidence-informed social work. Hence, this paper discusses the value of publishing protocols in social work research and presents the protocol of a randomized controlled trial that compares the effectiveness of integrative body-mind-spirit intervention with cognitive behavioral therapy for enhancing quality of life of patients with lung cancer and their family caregivers. The data collection process was still on-going at the time of manuscript submission.

The SMile Card: a computerised data card for multiple sclerosis patients. SMile Card Scientific Board.

PubMed

Mancardi, G L; Uccelli, M M; Sonnati, M; Comi, G; Milanese, C; De Vincentiis, A; Battaglia, M A

2000-04-01

The SMile Card was developed as a means for computerising clinical information for the purpose of transferability, accessibility, standardisation and compilation of a national database of demographic and clinical information about multiple sclerosis (MS) patients. In many European countries, centres for MS are organised independently from one another making collaboration, consultation and patient referral complicated. Only the more highly advanced clinical centres, generally located in large urban areas, have had the possibility to utilise technical possibilities for improving the organisation of patient clinical and research information, although independently from other centres. The information system, developed utilising the Visual Basic language for Microsoft Windows 95, stores information via a 'smart card' in a database which is initiated and updated utilising a microprocessor, located at each neurological clinic. The SMile Card, currently being tested in Italy, permits patients to carry with them all relevant medical information without limitations. Neurologists are able to access and update, via the microprocessor, the patient's entire medical history and MS-related information, including the complete neurological examination and laboratory test results. The SMile Card provides MS patients and neurologists with a complete computerised archive of clinical information which is accessible throughout the country. In addition, data from the SMile Card system can be exported to other database programs.

Computerised analysis of facial emotion expression in eating disorders

PubMed Central

2017-01-01

Background Problems with social-emotional processing are known to be an important contributor to the development and maintenance of eating disorders (EDs). Diminished facial communication of emotion has been frequently reported in individuals with anorexia nervosa (AN). Less is known about facial expressivity in bulimia nervosa (BN) and in people who have recovered from AN (RecAN). This study aimed to pilot the use of computerised facial expression analysis software to investigate emotion expression across the ED spectrum and recovery in a large sample of participants. Method 297 participants with AN, BN, RecAN, and healthy controls were recruited. Participants watched film clips designed to elicit happy or sad emotions, and facial expressions were then analysed using FaceReader. Results The finding mirrored those from previous work showing that healthy control and RecAN participants expressed significantly more positive emotions during the positive clip compared to the AN group. There were no differences in emotion expression during the sad film clip. Discussion These findings support the use of computerised methods to analyse emotion expression in EDs. The findings also demonstrate that reduced positive emotion expression is likely to be associated with the acute stage of AN illness, with individuals with BN showing an intermediate profile. PMID:28575109

Quality assurance audit: a prospective non-randomised trial of chemotherapy and radiotherapy for osteolymphoma (TROG 99.04/ALLG LY02).

PubMed

Christie, D; Le, T; Watling, K; Cornes, D; O'Brien, P; Hitchins, R

2009-04-01

A quality assurance (QA) audit of the Trans Tasman Radiation Oncology Group and Australasian Lymphoma and Leukaemia Group trial (TROG 99.04/ALLG LY02) began after accrual of 25 patients. The trial is a prospective non-randomized study of standard treatment for osteolymphoma. Data relating to informed consent, eligibility, chemotherapy and radiotherapy were reviewed. The audit showed a relatively low level of major variations from the protocol, with an overall rate of 3.6%. As this trial has accrued slowly over a long period, the concept of QA has also developed. Amendments were made to the protocol accordingly. In the future, QA procedures should be predetermined, conducted rapidly in real time, and appropriately funded in order to be relevant to the ongoing conduct of the trial.

The OPERA trial: a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

PubMed Central

2011-01-01

Background The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation. Trial Registration ISRCTN No: ISRCTN43769277 PMID:21288341

Vaccine Immunotherapy for Prostate Cancer

DTIC Science & Technology

2012-05-01

adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA...this award is to conduct a Phase II clinical trial (Study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols...suddenly prior to study treatment . And one patient previously reported as a screen failure became eligible and was treated. This subject was not

A data grid for imaging-based clinical trials

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

Chewing gum for the treatment of postoperative nausea and vomiting: a pilot randomized controlled trial.

PubMed

Darvall, J N; Handscombe, M; Leslie, K

2017-01-01

A novel treatment, chewing gum, may be non-inferior to ondansetron in inhibiting postoperative nausea and vomiting (PONV) in female patients after laparoscopic or breast surgery. In this pilot study, we tested the feasibility of a large randomized controlled trial. We randomized 94 female patients undergoing laparoscopic or breast surgery to ondansetron 4 mg i.v. or chewing gum if PONV was experienced in the postanaesthesia care unit (PACU). The primary outcome was full resolution of PONV, with non-inferiority defined as a difference between groups of <15% in a per protocol analysis. Secondary outcomes were PACU stay duration, anti-emetic rescue use, and acceptability of anti-emetic treatment. The feasibility of implementing the protocol in a larger trial was assessed. Postoperative nausea and vomiting in the PACU occurred in 13 (28%) ondansetron patients and 15 (31%) chewing gum patients (P=0.75). Three chewing gum patients could not chew gum when they developed PONV. On a per protocol basis, full resolution of PONV occurred in five of 13 (39%) ondansetron vs nine of 12 (75%) chewing gum patients [risk difference 37% (6.3-67%), P=0.07]. There was no difference in secondary outcomes between groups. Recruitment was satisfactory, the protocol was acceptable to anaesthetists and nurses, and data collection was complete. In this pilot trial, chewing gum was not inferior to ondansetron for treatment of PONV after general anaesthesia for laparoscopic or breast surgery in female patients. Our findings demonstrate the feasibility of a larger, multicentred randomized controlled trial to investigate this novel therapy. Australian New Zealand Clinical Trials Registry: ACTRN12615001327572. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery.

PubMed

Abdullah, Hairil Rizal; Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-08-04

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. NCT02921932 (ClinicalTrials.gov). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improving specialist drug prescribing in primary care using task and error analysis: an observational study.

PubMed

Chana, Narinder; Porat, Talya; Whittlesea, Cate; Delaney, Brendan

2017-03-01

Electronic prescribing has benefited from computerised clinical decision support systems (CDSSs); however, no published studies have evaluated the potential for a CDSS to support GPs in prescribing specialist drugs. To identify potential weaknesses and errors in the existing process of prescribing specialist drugs that could be addressed in the development of a CDSS. Semi-structured interviews with key informants followed by an observational study involving GPs in the UK. Twelve key informants were interviewed to investigate the use of CDSSs in the UK. Nine GPs were observed while performing case scenarios depicting requests from hospitals or patients to prescribe a specialist drug. Activity diagrams, hierarchical task analysis, and systematic human error reduction and prediction approach analyses were performed. The current process of prescribing specialist drugs by GPs is prone to error. Errors of omission due to lack of information were the most common errors, which could potentially result in a GP prescribing a specialist drug that should only be prescribed in hospitals, or prescribing a specialist drug without reference to a shared care protocol. Half of all possible errors in the prescribing process had a high probability of occurrence. A CDSS supporting GPs during the process of prescribing specialist drugs is needed. This could, first, support the decision making of whether or not to undertake prescribing, and, second, provide drug-specific parameters linked to shared care protocols, which could reduce the errors identified and increase patient safety. © British Journal of General Practice 2017.

CPOE in Iran--a viable prospect? Physicians' opinions on using CPOE in an Iranian teaching hospital.

PubMed

Kazemi, Alireza; Ellenius, Johan; Tofighi, Shahram; Salehi, Aref; Eghbalian, Fatemeh; Fors, Uno G

2009-03-01

In recent years, the theory that on-line clinical decision support systems can improve patients' safety among hospitalised individuals has gained greater acceptance. However, the feasibility of implementing such a system in a middle or low-income country has rarely been studied. Understanding the current prescription process and a proper needs assessment of prescribers can act as the key to successful implementation. The aim of this study was to explore physicians' opinions on the current prescription process, and the expected benefits and perceived obstacles to employ Computerised Physician Order Entry in an Iranian teaching hospital. Initially, the interview guideline was developed through focus group discussions with eight experts. Then semi-structured interviews were held with 19 prescribers. After verbatim transcription, inductive thematic analysis was performed on empirical data. Forty hours of on-looker observations were performed in different wards to explore the current prescription process. The current prescription process was identified as a physician-centred, top-down, model, where prescribers were found to mostly rely on their memories as well as being overconfident. Some errors may occur during different paper-based registrations, transcriptions and transfers. Physician opinions on Computerised Physician Order Entry were categorised into expected benefits and perceived obstacles. Confidentiality issues, reduction of medication errors and educational benefits were identified as three themes in the expected benefits category. High cost, social and cultural barriers, data entry time and problems with technical support emerged as four themes in the perceived obstacles category. The current prescription process has a high possibility of medication errors. Although there are different barriers confronting the implementation and continuation of Computerised Physician Order Entry in Iranian hospitals, physicians have a willingness to use them if these systems provide significant benefits. A pilot study in a limited setting and a comprehensive analysis of health outcomes and economic indicators should be performed, to assess the merits of introducing Computerised Physician Order Entry with decision support capabilities in Iran.

Effects of a Delphi consensus acupuncture treatment protocol on the levels of stress and vascular tone in women undergoing in-vitro fertilization: a randomized clinical trial protocol.

PubMed

Zhang, Yan; Phy, Jennifer; Scott-Johnson, Chris; Garos, Sheila; Orlando, Jennie; Prien, Samuel; Huang, Jaou-Chen

2017-04-04

The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture's impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to assess the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients' IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. ClinicalTrials NCT02591186 registered on October 7, 2015.

IL-6, Antioxidant Capacity and Muscle Damage Markers Following High-Intensity Interval Training Protocols

PubMed Central

2017-01-01

Abstract The aim of this study was to investigate changes of interleukin-6 (IL-6), total antioxidant capacity (TAC) and muscle damage markers (creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH)) in response to three different high-intensity interval training (HIIT) protocols of identical external work. Twelve moderately-trained males participated in the three HIIT trials which consisted of a warm-up, followed by 12 min of 15 s, 30 s or 60 s HIIT sequences with the work/rest ratio 1. The biochemical markers of inflammation, oxidative stress and muscle damage were analysed POST, 3 h and 24 h after the exercise. All HIIT protocols caused an immediate increase in IL-6, TAC, CK, myoglobin and LDH. The most pronounced between-trials differences were found for the POST-exercise changes in IL-6 (Effect size ± 90% confidence interval: 1.51 ± 0.63, 0.84 ± 0.34 and 1.80 ± 0.60 for the 15s/15s, 30s/30s and 60s/60s protocol, respectively) and myoglobin (1.11 ± 0.29, 0.45 ± 0.48 and 1.09 ± 0.22 for the 15s/15s, 30s/30s and 60s/60s protocol, respectively). There were no substantial between-trial differences in other biochemical variables. In conclusion, the 15s/15s and 60s/60s protocols might be preferred to the 30s/30s protocols in order to maximize the training stimulus. PMID:28469752

Computerised respiratory sounds can differentiate smokers and non-smokers.

PubMed

Oliveira, Ana; Sen, Ipek; Kahya, Yasemin P; Afreixo, Vera; Marques, Alda

2017-06-01

Cigarette smoking is often associated with the development of several respiratory diseases however, if diagnosed early, the changes in the lung tissue caused by smoking may be reversible. Computerised respiratory sounds have shown to be sensitive to detect changes within the lung tissue before any other measure, however it is unknown if it is able to detect changes in the lungs of healthy smokers. This study investigated the differences between computerised respiratory sounds of healthy smokers and non-smokers. Healthy smokers and non-smokers were recruited from a university campus. Respiratory sounds were recorded simultaneously at 6 chest locations (right and left anterior, lateral and posterior) using air-coupled electret microphones. Airflow (1.0-1.5 l/s) was recorded with a pneumotachograph. Breathing phases were detected using airflow signals and respiratory sounds with validated algorithms. Forty-four participants were enrolled: 18 smokers (mean age 26.2, SD = 7 years; mean FEV 1 % predicted 104.7, SD = 9) and 26 non-smokers (mean age 25.9, SD = 3.7 years; mean FEV 1 % predicted 96.8, SD = 20.2). Smokers presented significantly higher frequency at maximum sound intensity during inspiration [(M = 117, SD = 16.2 Hz vs. M = 106.4, SD = 21.6 Hz; t(43) = -2.62, p = 0.0081, d z  = 0.55)], lower expiratory sound intensities (maximum intensity: [(M = 48.2, SD = 3.8 dB vs. M = 50.9, SD = 3.2 dB; t(43) = 2.68, p = 0.001, d z  = -0.78)]; mean intensity: [(M = 31.2, SD = 3.6 dB vs. M = 33.7,SD = 3 dB; t(43) = 2.42, p = 0.001, d z  = 0.75)] and higher number of inspiratory crackles (median [interquartile range] 2.2 [1.7-3.7] vs. 1.5 [1.2-2.2], p = 0.081, U = 110, r = -0.41) than non-smokers. Significant differences between computerised respiratory sounds of smokers and non-smokers have been found. Changes in respiratory sounds are often the earliest sign of disease. Thus, computerised respiratory sounds might be a promising measure to early detect smoking related respiratory diseases.

SU-F-P-13: NRG Oncology Medical Physics Manpower Survey Quantifying Support Demands for Multi Institutional Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monroe, J; Case Western Reserve University; Boparai, K

Purpose: A survey was taken by NRG Oncology to assess Full Time Equivalent (FTE) contributions to multi institutional clinical trials by medical physicists.No current quantification of physicists’ efforts in FTE units associated with clinical trials is available. The complexity of multi-institutional trials increases with new technologies and techniques. Proper staffing may directly impact the quality of trial data and outcomes. The demands on physics time supporting clinical trials needs to be assessed. Methods: The NRG Oncology Medical Physicist Subcommittee created a sixteen question survey to obtain this FTE data. IROC Houston distributed the survey to their list of 1802 contactmore » physicists. Results: After three weeks, 363 responded (20.1% response). 187 (51.5%) institutions reporting external beam participation were processed. There was a wide range in number of protocols active and supported at each institution. Of the 187 clinics, 134 (71.7%) participate in 0 to 10 trials, 28 (15%) in 11 to 20 trials, 10 (5.3%) in 21 to 30 trials, 9 (4.8%) had 40 to 75 trials. On average, physicist spent 2.7 hours (SD: 6.0) per week supervising or interacting with clinical trial staff. 1.25 hours (SD: 3.37), 1.83 hours (SD: 4.13), and 0.64 hours(SD: 1.13) per week were spent on patient simulation, reviewing treatment plans, and maintaining a DICOM server, respectively. For all protocol credentialing activities, physicist spent an average of 37.05 hours (SD: 96.94) yearly. To support dosimetrists, clinicians, and therapists, physicist spend on average 2.07 hours (SD: 3.52) per week just reading protocols. Physicist attended clinical trial meetings for on average 1.13 hours (SD: 1.85) per month. Conclusion: Responding physicists spend a nontrivial amount of time: 8.8 hours per week (0.22 FTE) supporting, on average, 9 active multi-institutional clinical trials.« less

Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates.

PubMed

Furness, Peter N; Philpott, Carl M; Chorbadjian, Mary T; Nicholson, Michael L; Bosmans, Jean-Louis; Corthouts, Bob L; Bogers, Johannes J P M; Schwarz, Anke; Gwinner, Wilfried; Haller, Hermann; Mengel, Michael; Seron, Daniel; Moreso, Francesc; Cañas, Conception

2003-09-27

Clinical trials in renal transplantation must use surrogate markers of long-term graft survival if conclusions are to be drawn at acceptable speed and cost. Morphologic changes in transplant biopsies provide the earliest available evidence of damage, and "protocol" biopsies from stable grafts can be used to reduce the number of patients needed in clinical trials. This approach has been inhibited by concerns over safety, but the risk of biopsy of a stable kidney, with no active inflammation or acute functional impairment, has never been formally estimated. In accordance with a predefined set of questions, a retrospective audit of a sequential series of protocol biopsies was performed in four major transplant centers. A total of 2,127 biopsy events were assessed for major complications, and 1,486 were assessed for minor ones. There were no deaths. One graft was lost, under circumstances indicating that the loss should have been prevented. Three episodes of hemorrhage required direct intervention. Three further patients required transfusion. There were two episodes of peritonitis, but one was arguably an unrelated event. All serious complications presented within 4 hr of biopsy. The incidence of clinically significant complications after protocol biopsy of a stable renal transplant is low. Direct benefits to the patients concerned (irrespective of the benefit that may accrue in clinical trials) were not formally assessed but seem likely to outweigh the risk of the procedure. We believe that it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care.

Quality assurance of research protocols conducted in the community: the National Institute on Drug Abuse Clinical Trials Network experience.

PubMed

Rosa, Carmen; Campbell, Aimee; Kleppinger, Cynthia; Sampson, Royce; Tyson, Clare; Mamay-Gentilin, Stephanie

2009-04-01

Quality assurance (QA) of clinical trials is essential to protect the welfare of trial participants and the integrity of the data collected. However, there is little detailed information available on specific procedures and outcomes of QA monitoring for clinical trials. This article describes the experience of the National Institute on Drug Abuse's (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) in devising and implementing a three-tiered QA model for rigorous multi-site randomized clinical trials implemented in community-based substance abuse treatment programs. The CTN QA model combined local and national resources and was developed to address the unique needs of clinical trial sites with limited research experience. The authors reviewed internal records maintained by the sponsor, a coordinating site (Lead Nodes), and a local site detailing procedural development, training sessions, protocol violation monitoring, and site visit reporting. Between January 2001 and September 2005, the CTN implemented 21 protocols, of which 18 were randomized clinical trials, one was a quality improvement study and two were surveys. Approximately 160 community-based treatment programs participated in the 19 studies that were monitored, with a total of 6560 participants randomized across the sites. During this time 1937 QA site visits were reported across the three tiers of monitoring and the cost depended on the location of the sites and the salaries of the staff involved. One study reported 109 protocol violations (M = 15.6). Examples are presented to highlight training, protocol violation monitoring, site visit frequency and intensity and cost considerations. : QA data from the entire network were not easily available for review as much of the data were not electronically accessible. The authors reviewed and discussed a representative sample of internal data from the studies and participating sites. The lessons learned from the CTN's experience include the need for balancing thoroughness with efficiency, monitoring early, assessing research staff abilities in order to judge the need for proactive, focused attention, providing targeted training sessions, and developing flexible tools. The CTN model can work for sponsors overseeing studies at sites with limited research experience that require more frequent, in-depth monitoring. We recommend that sponsors not develop a rigid monitoring approach, but work with the study principal investigators to determine the intensity of monitoring needed depending on trial complexity, the risks of the intervention(s), and the experience of the staff with clinical research. After careful evaluation, sponsors should then determine the best approach to site monitoring and what resources will be needed.

Quality assurance of research protocols conducted in the community: The National Institute on Drug Abuse Clinical Trials Network Experience

PubMed Central

Rosa, Carmen; Campbell, Aimee; Kleppinger, Cynthia; Sampson, Royce; Tyson, Clare; Mamay-Gentilin, Stephanie

2009-01-01

Background: Quality assurance (QA) of clinical trials is essential to protect the welfare of trial participants and the integrity of the data collected. However, there is little detailed information available on specific procedures and outcomes of QA monitoring for clinical trials. Purpose: This article describes the experience of the National Institute on Drug Abuse's (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) in devising and implementing a three-tiered QA model for rigorous multi-site randomized clinical trials implemented in community-based substance abuse treatment programs. The CTN QA model combined local and national resources and was developed to address the unique needs of clinical trial sites with limited research experience. Methods: The authors reviewed internal records maintained by the sponsor, a coordinating site (Lead Nodes), and a local site detailing procedural development, training sessions, protocol violation monitoring, and site visit reporting. Results: Between January 2001 and September 2005, the CTN implemented 21 protocols, of which 18 were randomized clinical trials, one was a quality improvement study and two were surveys. Approximately 160 community-based treatment programs participated in the 19 studies that were monitored, with a total of 6560 participants randomized across the sites. During this time 1937 QA site visits were reported across the three tiers of monitoring and the cost depended on the location of the sites and the salaries of the staff involved. One study reported 109 protocol violations (M = 15.6). Examples are presented to highlight training, protocol violation monitoring, site visit frequency and intensity and cost considerations. Limitations: QA data from the entire network were not easily available for review as much of the data were not electronically accessible. The authors reviewed and discussed a representative sample of internal data from the studies and participating sites. Conclusions: The lessons learned from the CTN's experience include the need for balancing thoroughness with efficiency, monitoring early, assessing research staff abilities in order to judge the need for proactive, focused attention, providing targeted training sessions, and developing flexible tools. The CTN model can work for sponsors overseeing studies at sites with limited research experience that require more frequent, in-depth monitoring. We recommend that sponsors not develop a rigid monitoring approach, but work with the study principal investigators to determine the intensity of monitoring needed depending on trial complexity, the risks of the intervention(s), and the experience of the staff with clinical research. After careful evaluation, sponsors should then determine the best approach to site monitoring and what resources will be needed. PMID:19342468

Standardized terminology for clinical trial protocols based on top-level ontological categories.

PubMed

Heller, B; Herre, H; Lippoldt, K; Loeffler, M

2004-01-01

This paper describes a new method for the ontologically based standardization of concepts with regard to the quality assurance of clinical trial protocols. We developed a data dictionary for medical and trial-specific terms in which concepts and relations are defined context-dependently. The data dictionary is provided to different medical research networks by means of the software tool Onto-Builder via the internet. The data dictionary is based on domain-specific ontologies and the top-level ontology of GOL. The concepts and relations described in the data dictionary are represented in natural language, semi-formally or formally according to their use.

Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial.

PubMed

Kacmarek, Robert M; Villar, Jesús; Sulemanji, Demet; Montiel, Raquel; Ferrando, Carlos; Blanco, Jesús; Koh, Younsuck; Soler, Juan Alfonso; Martínez, Domingo; Hernández, Marianela; Tucci, Mauro; Borges, Joao Batista; Lubillo, Santiago; Santos, Arnoldo; Araujo, Juan B; Amato, Marcelo B P; Suárez-Sipmann, Fernando

2016-01-01

The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. A prospective, multicenter, pilot, randomized controlled trial. A network of 20 multidisciplinary ICUs. Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2≥0.5, positive end-expiratory pressure ≥10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.

Development of Uniform Protocol for Alopecia Areata Clinical Trials.

PubMed

Solomon, James A

2015-11-01

Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies.

Computerisation of diabetic clinic records.

PubMed Central

Watkins, G B; Sutcliffe, T; Pyke, D A; Watkins, P J

1980-01-01

A simple system for putting diabetic records on a computer file is achieved by using stationery that combines the usual handwritten records (not computerised) with the minimum of essential data suitable for punching on to computer tape. The record may be brought up to date at a selected time time interval. This simple, cheap system has been in use in a busy clinic for six years. The information on about 8000 diabetics now held in the computer file is used chiefly to help research by creating registers of patients with specified characteristics, such as treatment, heredity complications, and pregnancy. A complete up-to-date index of the entire clinic population is always available, and routine clinic statistics are returned every six months. PMID:7437814

What Do We Really Know About the Safety of Tai Chi?: A Systematic Review of Adverse Event Reports in Randomized Trials

PubMed Central

Wayne, Peter M.; Berkowitz, Danielle L.; Litrownik, Daniel E.; Buring, Julie E.; Yeh, Gloria Y.

2014-01-01

Objective Systematically review frequency and quality of adverse event (AE) reports in randomized clinical trials (RCTs) of Tai Chi (TC). Data Sources Electronic searches of PubMed/MEDLINE and additional databases from inception through March 2013 of English-language RCTs. Search terms were tai chi, taiji, tai chi chuan. Data were independently extracted by two investigators. Study Selection We included all available randomized controlled trials (RCTs) that were published in English and used Tai Chi as an intervention. Inclusion and exclusion of studies were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data Extraction Eligible RCTs were categorized with respect to AE reporting: 1) No mention of protocols for monitoring AEs or reports of AEs; 2) Reports of AEs either with or without explicit protocols for monitoring AEs. Data Synthesis 153 eligible RCTs were identified, most targeting older adults. Only 50 eligible trials (33%) included reporting of AEs, and of these, only 18 trials (12% overall) also reported an explicit AE monitoring protocol. Protocols varied with respect to rigor of systematic monitoring in both Tai Chi and comparison groups. Reported AEs were typically minor and expected, and primarily musculoskeletal related (e.g., knee and back pain); no intervention-related serious AEs were reported. Conclusions Tai Chi is unlikely to result in serious adverse events, but may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of Tai Chi. PMID:24878398

Reporting guidance considerations from a statistical perspective: overview of tools to enhance the rigour of reporting of randomised trials and systematic reviews.

PubMed

Hutton, Brian; Wolfe, Dianna; Moher, David; Shamseer, Larissa

2017-05-01

Research waste has received considerable attention from the biomedical community. One noteworthy contributor is incomplete reporting in research publications. When detailing statistical methods and results, ensuring analytic methods and findings are completely documented improves transparency. For publications describing randomised trials and systematic reviews, guidelines have been developed to facilitate complete reporting. This overview summarises aspects of statistical reporting in trials and systematic reviews of health interventions. A narrative approach to summarise features regarding statistical methods and findings from reporting guidelines for trials and reviews was taken. We aim to enhance familiarity of statistical details that should be reported in biomedical research among statisticians and their collaborators. We summarise statistical reporting considerations for trials and systematic reviews from guidance documents including the Consolidated Standards of Reporting Trials (CONSORT) Statement for reporting of trials, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Statement for trial protocols, the Statistical Analyses and Methods in the Published Literature (SAMPL) Guidelines for statistical reporting principles, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement for systematic reviews and PRISMA for Protocols (PRISMA-P). Considerations regarding sharing of study data and statistical code are also addressed. Reporting guidelines provide researchers with minimum criteria for reporting. If followed, they can enhance research transparency and contribute improve quality of biomedical publications. Authors should employ these tools for planning and reporting of their research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Design of a Web-tool for diagnostic clinical trials handling medical imaging research.

PubMed

Baltasar Sánchez, Alicia; González-Sistal, Angel

2011-04-01

New clinical studies in medicine are based on patients and controls using different imaging diagnostic modalities. Medical information systems are not designed for clinical trials employing clinical imaging. Although commercial software and communication systems focus on storage of image data, they are not suitable for storage and mining of new types of quantitative data. We sought to design a Web-tool to support diagnostic clinical trials involving different experts and hospitals or research centres. The image analysis of this project is based on skeletal X-ray imaging. It involves a computerised image method using quantitative analysis of regions of interest in healthy bone and skeletal metastases. The database is implemented with ASP.NET 3.5 and C# technologies for our Web-based application. For data storage, we chose MySQL v.5.0, one of the most popular open source databases. User logins were necessary, and access to patient data was logged for auditing. For security, all data transmissions were carried over encrypted connections. This Web-tool is available to users scattered at different locations; it allows an efficient organisation and storage of data (case report form) and images and allows each user to know precisely what his task is. The advantages of our Web-tool are as follows: (1) sustainability is guaranteed; (2) network locations for collection of data are secured; (3) all clinical information is stored together with the original images and the results derived from processed images and statistical analysis that enable us to perform retrospective studies; (4) changes are easily incorporated because of the modular architecture; and (5) assessment of trial data collected at different sites is centralised to reduce statistical variance.

Shoulder function and work disability after decompression surgery for subacromial impingement syndrome: a randomised controlled trial of physiotherapy exercises and occupational medical assistance.

PubMed

Svendsen, Susanne W; Christiansen, David H; Haahr, Jens Peder; Andrea, Linda C; Frost, Poul

2014-06-21

Surgery for subacromial impingement syndrome is often performed in working age and postoperative physiotherapy exercises are widely used to help restore function. A recent Danish study showed that 10% of a nationwide cohort of patients retired prematurely within two years after surgery. Few studies have compared effects of different postoperative exercise programmes on shoulder function, and no studies have evaluated workplace-oriented interventions to reduce postoperative work disability. This study aims to evaluate the effectiveness of physiotherapy exercises and occupational medical assistance compared with usual care in improving shoulder function and reducing postoperative work disability after arthroscopic subacromial decompression. The study is a mainly pragmatic multicentre randomised controlled trial. The trial is embedded in a cohort study of shoulder patients referred to public departments of orthopaedic surgery in Central Denmark Region. Patients aged ≥18-≤63 years, who still have shoulder symptoms 8-12 weeks after surgery, constitute the study population. Around 130 participants are allocated to: 1) physiotherapy exercises, 2) occupational medical assistance, 3) physiotherapy exercises and occupational medical assistance, and 4) usual care. Intervention manuals allow individual tailoring. Primary outcome measures include Oxford Shoulder Score and sickness absence due to symptoms from the operated shoulder. Randomisation is computerised with allocation concealment by randomly permuted block sizes. Statistical analyses will primarily be performed according to the intention-to-treat principle. The paper presents the rationale, design, methods, and operational aspects of the Shoulder Intervention Project (SIP). SIP evaluates a new rehabilitation approach, where physiotherapy and occupational interventions are provided in continuity of surgical episodes of care. If successful, the project may serve as a model for rehabilitation of surgical shoulder patients. Current Controlled Trials ISRCTN55768749.

The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures.

PubMed

Wright, Melanie C; Taekman, Jeffrey M; Barber, Linda; Hobbs, Gene; Newman, Mark F; Stafford-Smith, Mark

2005-12-01

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

Contextual information management: An example of independent-checking in the review of laboratory-based bloodstain pattern analysis.

PubMed

Osborne, Nikola K P; Taylor, Michael C

2018-05-01

This article describes a New Zealand forensic agency's contextual information management protocol for bloodstain pattern evidence examined in the laboratory. In an effort to create a protocol that would have minimal impact on current work-flow, while still effectively removing task-irrelevant contextual information, the protocol was designed following an in-depth consultation with management and forensic staff. The resulting design was for a protocol of independent-checking (i.e. blind peer-review) where the checker's interpretation of the evidence is conducted in the absence of case information and the original examiner's notes or interpretation(s). At the conclusion of a ten-case trial period, there was widespread agreement that the protocol had minimal impact on the number of people required, the cost, or the time to complete an item examination. The agency is now looking to adopt the protocol into standard operating procedures and in some cases the protocol has been extended to cover other laboratory-based examinations (e.g. fabric damage, shoeprint examination, and physical fits). The protocol developed during this trial provides a useful example for agencies seeking to adopt contextual information management into their workflow. Copyright © 2018 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.

Data Acquisition for a Patient-directed Intervention Protocol in the Dynamic Intensive Care Unit Setting

PubMed Central

Chlan, Linda; Patterson, Robert P.; Heiderscheit, Annie

2011-01-01

Methods to easily, accurately, and efficiently obtain data in an ICU-based clinical trial can be challenging in this high-tech setting. Patient medical status and the dynamic nature of this clinical setting further complicates data collection. The purpose of this paper is to describe the modifications of commercially available headphones and the application of a data logging device to capture frequency and length of protocol use (music listening or headphones only for noise cancellation) without burdening participants or busy ICU nurses. With the automatic capture of protocol use by research participants, there have been no instances of lost data for this clinical trial. PMID:21382515

Data acquisition for a patient-directed intervention protocol in the dynamic intensive care unit setting.

PubMed

Chlan, Linda; Patterson, Robert P; Heiderscheit, Annie

2011-07-01

Methods to easily, accurately, and efficiently obtain data in an ICU-based clinical trial can be challenging in this high-tech setting. Patient medical status and the dynamic nature of this clinical setting further complicate data collection. The purpose of this paper is to describe the modifications of commercially available headphones and the application of a data logging device to capture frequency and length of protocol use (music listening or headphones only for noise cancellation) without burdening participants or busy ICU nurses. With the automatic capture of protocol use by research participants, there have been no instances of lost data for this clinical trial. Copyright © 2011 Elsevier Inc. All rights reserved.

Ancillary Care in South African HIV Vaccine Trials: Addressing Needs, Drafting Protocols, and Engaging Community

PubMed Central

Slack, Catherine M.

2014-01-01

There has been debate about sponsor-investigator ethical responsibilities to address participants’ medical needs in trials in resource-constrained contexts. Certain ethical guidelines make detailed recommendations. This study explored whether ethical guideline recommendations for care in HIV vaccine trials were being met, and whether stakeholders were facing difficulties addressed by guidelines. It sampled key stakeholders involved in two trials across five sites in South Africa, and reviewed relevant documentation. It concluded that sites were largely meeting guideline recommendations for addressing needs, with some exceeding these. Recommendations for writing protocols were only partially achieved. Recommendations for engaging participating community were mostly met, except for “moral negotiation” recommendations. Suggestions are made to strengthen practices, and to improve guidelines so they address empirical concerns. PMID:24572086

Ancillary care in South African HIV vaccine trials: addressing needs, drafting protocols, and engaging community.

PubMed

Slack, Catherine M

2014-02-01

There has been debate about sponsor-investigator ethical responsibilities to address participants' medical needs in trials in resource-constrained contexts. Certain ethical guidelines make detailed recommendations. This study explored whether ethical guideline recommendations for care in HIV vaccine trials were being met, and whether stakeholders were facing difficulties addressed by guidelines. It sampled key stakeholders involved in two trials across five sites in South Africa, and reviewed relevant documentation. It concluded that sites were largely meeting guideline recommendations for addressing needs, with some exceeding these. Recommendations for writing protocols were only partially achieved. Recommendations for engaging participating community were mostly met, except for "moral negotiation" recommendations. Suggestions are made to strengthen practices, and to improve guidelines so they address empirical concerns.

Osteopathic manipulative treatment and pain in preterms: study protocol for a randomised controlled trial.

PubMed

Cerritelli, Francesco; Cicchitti, Luca; Martelli, Marta; Barlafante, Gina; Renzetti, Cinzia; Pizzolorusso, Gianfranco; Lupacchini, Mariacristina; D'Orazio, Marianna; Marinelli, Benedetta; Cozzolino, Vincenzo; Fusilli, Paola; D'Incecco, Carmine

2015-03-08

Recent evidence proved the necessity to improve health care and pain management in newborns. Osteopathic manipulative treatment (OMT) has been largely used to treat painful syndromes as well as term and preterm newborns. Recent studies have demonstrated positive results of osteopathy in reducing length of stay and costs. However, no trials were carried out on pain in newborns. The aim of the present clinical trial is to explore the effectiveness of osteopathic treatment in reducing pain in a sample of preterms. A three-armed single blinded placebo-control randomised controlled trial protocol has been designed to primarily evaluate the extent to which OMT is effective in reducing pain in preterms. One hundred and twenty newborns will be enrolled from one tertiary neonatal intensive care unit in central Italy and randomised in three groups: study, sham and control. The study group will be further prospectively randomised in two subgroups: experienced osteopaths and students. All preterms will receive standard medical care. Osteopathic treatment will be applied to the study group only whilst 'soft touch' will be administer to the sham group only. Newborns will undergo manual sessions once a week for the entire period of hospitalisation. Blinding will be assured for neonatal staff and outcome assessor. Primary outcome will be the mean difference in baseline score changes of PIPP questionnaire between discharge and entry among the three groups. Secondary outcomes will be: mean difference in length of stay and costs between groups. Statistical analyses will use per-protocol analysis method. Missing data will be handled using last observation carried forward imputation technique. The present single blinded randomised controlled trial has been designed to explore potential advantages of OMT in the management of newborns' pain. Currently, based on a patient-centred need-based approach, this research will be looking at the benefit of osteopathic care rather than the efficacy of a specific technique or a pre-determined protocol. The protocol has been registered on ClinicalTrials.gov ( NCT02146677 ) on 20 May 2014.

Patient perspectives: Kundalini yoga meditation techniques for psycho-oncology and as potential therapies for cancer.

PubMed

Shannahoff-Khalsa, David S

2005-03-01

The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self-directed integrative care approach.

Efficacy of the unified protocol for the treatment of emotional disorders in the Spanish public mental health system using a group format: study protocol for a multicenter, randomized, non-inferiority controlled trial.

PubMed

Osma, Jorge; Suso-Ribera, Carlos; García-Palacios, Azucena; Crespo-Delgado, Elena; Robert-Flor, Cristina; Sánchez-Guerrero, Ana; Ferreres-Galan, Vanesa; Pérez-Ayerra, Luisa; Malea-Fernández, Amparo; Torres-Alfosea, Mª Ángeles

2018-03-12

Emotional disorders, which include both anxiety and depressive disorders, are the most prevalent psychological disorders according to recent epidemiological studies. Consequently, public costs associated with their treatment have become a matter of concern for public health systems, which face long waiting lists. Because of their high prevalence in the population, finding an effective treatment for emotional disorders has become a key goal of today's clinical psychology. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders might serve the aforementioned purpose, as it can be applied to a variety of disorders simultaneously and it can be easily performed in a group format. The study is a multicenter, randomized, non-inferiority controlled clinical trial. Participants will be 220 individuals with emotional disorders, who are randomized to either a treatment as usual (individual cognitive behavioral therapy) or to a Unified Protocol condition in group format. Depression, anxiety, and diagnostic criteria are the primary outcome measures. Secondary measures include the assessment of positive and negative affect, anxiety control, personality traits, overall adjustment, and quality of life. An analysis of treatment satisfaction is also conducted. Assessment points include baseline, post-treatment, and three follow-ups at 3, 6, and 12 months. To control for missing data and possible biases, intention-to-treat and per-protocol analyses will be performed. This is the first randomized, controlled clinical trial to test the effectiveness of a transdiagnostic intervention in a group format for the treatment of emotional disorders in public settings in Spain. Results obtained from this study may have important clinical, social, and economic implications for public mental health settings in Spain. Retrospectively registered at https://clinicaltrials.gov/ . Trial NCT03064477 (March 10, 2017). The trial is active and recruitment is ongoing. Recruitment is expected to finish by January 2020.

Radiotherapy for Prostate Cancer: is it 'what you do' or 'the way that you do it'? A UK Perspective on Technique and Quality Assurance.

PubMed

Mason, M D; Moore, R; Jones, G; Lewis, G; Donovan, J L; Neal, D E; Hamdy, F C; Lane, J A; Staffurth, J N

2016-09-01

The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history of prostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial. The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localised prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n = 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era. There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outlining review showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of the prostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints in ProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent. The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. Copyright © 2016. Published by Elsevier Ltd.

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

PubMed Central

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed. PMID:20573639

Protocol deviations before and after IV tPA in community hospitals

PubMed Central

Adelman, Eric E.; Scott, Phillip A.; Skolarus, Lesli E.; Fox, Allison K.; Frederiksen, Shirley M.; Meurer, William J.

2015-01-01

Background Protocol deviations before and after tPA treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict protocol deviations. We examined predictors of protocol deviations and the effects of protocol violations on symptomatic intracerebral hemorrhage. Methods We used data from the INSTINCT trial, a cluster-randomized, controlled trial evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use in 24 Michigan community hospitals, to review tPA treatments between 2007 and 2010. Protocol violations were defined as deviations from the standard tPA protocol, both before and after treatment. Multi-level logistic regression models were fitted to determine if patient and hospital variables were associated with pre-treatment or post-treatment protocol deviations. Results During the study, 557 patients (mean age 70; 52% male; median NIHSS 12) were treated with tPA. Protocol deviations occurred in 233 (42%) patients: 16% had pre-treatment deviations, 35% had post-treatment deviations, and 9% had both. The most common protocol deviations included elevated post-treatment blood pressure, antithrombotic agent use within 24 hours of treatment, and elevated pre-treatment blood pressure. Protocol deviations were not associated with symptomatic intracerebral hemorrhage, stroke severity, or hospital factors. Older age was associated with pre-treatment protocol deviations (adjusted OR 0.52; 95% confidence interval 0.30-0.92). Pre-treatment deviations were associated with post-treatment deviations (adjusted OR 3.20; 95% confidence interval 1.91-5.35). Conclusions Protocol deviations were not associated with symptomatic intracerebral hemorrhage. Aside from age, patient and hospital factors were not associated with protocol deviations. PMID:26419527

Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial.

PubMed

Wall, Peter Dh; Dickenson, Edward J; Robinson, David; Hughes, Ivor; Realpe, Alba; Hobson, Rachel; Griffin, Damian R; Foster, Nadine E

2016-10-01

Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility. In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events. The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12-26 weeks in 6-10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events. PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839). ISRCTN 09754699. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Comparison of Critical Power and W' Derived From 2 or 3 Maximal Tests.

PubMed

Simpson, Len Parker; Kordi, Mehdi

2017-07-01

Typically, accessing the asymptote (critical power; CP) and curvature constant (W') parameters of the hyperbolic power-duration relationship requires multiple constant-power exhaustive-exercise trials spread over several visits. However, more recently single-visit protocols and personal power meters have been used. This study investigated the practicality of using a 2-trial, single-visit protocol in providing reliable CP and W' estimates. Eight trained cyclists underwent 3- and 12-min maximal-exercise trials in a single session to derive (2-trial) CP and W' estimates. On a separate occasion a 5-min trial was performed, providing a 3rd trial to calculate (3-trial) CP and W'. There were no differences in CP (283 ± 66 vs 282 ± 65 W) or W' (18.72 ± 6.21 vs 18.27 ± 6.29 kJ) obtained from either the 2-trial or 3-trial method, respectively. After 2 familiarization sessions (completing a 3- and a 12-min trial on both occasions), both CP and W' remained reliable over additional separate measurements. The current study demonstrates that after 2 familiarization sessions, reliable CP and W' parameters can be obtained from trained cyclists using only 2 maximal-exercise trials. These results offer practitioners a practical, time-efficient solution for incorporating power-duration testing into applied athlete support.

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

PubMed Central

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-01-01

Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. Trial registration number ISRCTN03978701. PMID:26297361

Inconsistencies in quality of life data collection in clinical trials: a potential source of bias? Interviews with research nurses and trialists.

PubMed

Kyte, Derek; Ives, Jonathan; Draper, Heather; Keeley, Thomas; Calvert, Melanie

2013-01-01

Patient-reported outcomes (PROs), such as health-related quality of life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical trials, are valued by patients, and may inform important decisions in the clinical setting. It is of concern, therefore, that preliminary evidence, gained from group discussions at UK-wide Medical Research Council (MRC) quality of life training days, suggests there are inconsistent standards of HRQL data collection in trials and appropriate training and education is often lacking. Our objective was to investigate these reports, to determine if they represented isolated experiences, or were indicative of a potentially wider problem. We undertook a qualitative study, conducting 26 semi-structured interviews with research nurses, data managers, trial coordinators and research facilitators involved in the collection and entry of HRQL data in clinical trials, across one primary care NHS trust, two secondary care NHS trusts and two clinical trials units in the UK. We used conventional content analysis to analyze and interpret our data. Our study participants reported (1) inconsistent standards in HRQL measurement, both between, and within, trials, which appeared to risk the introduction of bias; (2), difficulties in dealing with HRQL data that raised concern for the well-being of the trial participant, which in some instances led to the delivery of non-protocol driven co-interventions, (3), a frequent lack of HRQL protocol content and appropriate training and education of trial staff, and (4) that HRQL data collection could be associated with emotional and/or ethical burden. Our findings suggest there are inconsistencies in the standards of HRQL data collection in some trials resulting from a general lack of HRQL-specific protocol content, training and education. These inconsistencies could lead to biased HRQL trial results. Future research should aim to develop HRQL guidelines and training programmes aimed at supporting researchers to carry out high quality data collection.

Inconsistencies in Quality of Life Data Collection in Clinical Trials: A Potential Source of Bias? Interviews with Research Nurses and Trialists

PubMed Central

Kyte, Derek; Ives, Jonathan; Draper, Heather; Keeley, Thomas; Calvert, Melanie

2013-01-01

Background Patient-reported outcomes (PROs), such as health-related quality of life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical trials, are valued by patients, and may inform important decisions in the clinical setting. It is of concern, therefore, that preliminary evidence, gained from group discussions at UK-wide Medical Research Council (MRC) quality of life training days, suggests there are inconsistent standards of HRQL data collection in trials and appropriate training and education is often lacking. Our objective was to investigate these reports, to determine if they represented isolated experiences, or were indicative of a potentially wider problem. Methods And Findings We undertook a qualitative study, conducting 26 semi-structured interviews with research nurses, data managers, trial coordinators and research facilitators involved in the collection and entry of HRQL data in clinical trials, across one primary care NHS trust, two secondary care NHS trusts and two clinical trials units in the UK. We used conventional content analysis to analyze and interpret our data. Our study participants reported (1) inconsistent standards in HRQL measurement, both between, and within, trials, which appeared to risk the introduction of bias; (2), difficulties in dealing with HRQL data that raised concern for the well-being of the trial participant, which in some instances led to the delivery of non-protocol driven co-interventions, (3), a frequent lack of HRQL protocol content and appropriate training and education of trial staff, and (4) that HRQL data collection could be associated with emotional and/or ethical burden. Conclusions Our findings suggest there are inconsistencies in the standards of HRQL data collection in some trials resulting from a general lack of HRQL-specific protocol content, training and education. These inconsistencies could lead to biased HRQL trial results. Future research should aim to develop HRQL guidelines and training programmes aimed at supporting researchers to carry out high quality data collection. PMID:24124580

Cost-effectiveness of an intensive group training protocol compared to physiotherapy guideline care for sub-acute and chronic low back pain: design of a randomised controlled trial with an economic evaluation. [ISRCTN45641649

PubMed Central

van der Roer, Nicole; van Tulder, Maurits W; Barendse, Johanna M; van Mechelen, Willem; Franken, Willemien K; Ooms, Arjan C; de Vet, Henrica CW

2004-01-01

Background Low back pain is a common disorder in western industrialised countries and the type of treatments for low back pain vary considerably. Methods In a randomised controlled trial the cost-effectiveness and cost-utility of an intensive group training protocol versus physiotherapy guideline care for sub-acute and chronic low back pain patients is evaluated. Patients with back pain for longer than 6 weeks who are referred to physiotherapy care by their general practitioner or medical specialist are included in the study. The intensive group training protocol combines exercise therapy with principles of behavioural therapy ("graded activity") and back school. This training protocol is compared to physiotherapy care according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy. Primary outcome measures are general improvement, pain intensity, functional status, work absenteeism and quality of life. The direct and indirect costs will be assessed using cost diaries. Patients will complete questionnaires at baseline and 6, 13, 26 and 52 weeks after randomisation. Discussion No trials are yet available that have evaluated the effect of an intensive group training protocol including behavioural principles and back school in a primary physiotherapy care setting and no data on cost-effectiveness and cost-utility are available. PMID:15560843

Cultural differences in distraction processing: influence of context at retrieval.

PubMed

Ngo, Ka Wai Joan; Amer, Tarek; Man, Louisa; Hasher, Lynn

2018-06-04

Cultural differences in information processing affect perceptual judgment, attention, and memory. We investigated whether cultural differences in processing patterns, specifically East Asian participants' tendency to encode holistically, compared to Western tendencies to process analytically, affect performance on an implicit memory test. First, participants completed a 1-back task on pictures with superimposed distracting words. After a delay filled with a computerised Corsi block task, they performed a word fragment task in which some fragments could be completed with the distracting words from the 1-back task. Critically, fragments were presented with the same pictures as previously seen (matched condition), with no pictures (control condition), or with pictures from other trials on the 1-back task (mismatched condition). Non-Asian Canadian participants showed virtually no priming for distraction, independent of the reinstatement of encoding context. East Asian Canadian participants showed superior priming for fragments that had been paired with their original pictures. They did not show evidence of a detriment for the mismatched, relative to control, condition.

The NIDA Methamphetamine Clinical Trials Group: a strategy to increase clinical trials research capacity.

PubMed

Elkashef, Ahmed; Rawson, Richard A; Smith, Edwina; Pearce, Valerie; Flammino, Frank; Campbell, Jan; Donovick, Roger; Gorodetzky, Charles; Haning, William; Mawhinney, Joseph; McCann, Michael; Weis, Dennis; Williams, Lorie; Ling, Walter; Vocci, Frank

2007-04-01

In order to increase the number of investigative teams and sites conducting research on pharmacological treatments for methamphetamine use disorders, the National Institute on Drug Abuse (NIDA) established an infrastructure of clinical sites in areas where methamphetamine addiction is prevalent. This multi-site infrastructure would serve to run multiple Phases II and III protocols effectively and expeditiously. NIDA collaborated with investigators from the University of California at Los Angeles (UCLA) to set up the Methamphetamine Clinical Trials Group (MCTG). This paper describes the development process, as well as data from a test trial to assess the capability of research-naive sites to recruit research participants and conduct study procedures according to research protocol. Subsequent trials are also described. A total of 151 candidates signed consent; 65 individuals were enrolled and 35 (53.8%) completed the 12 weeks' behavioral trial. Self-reported substance use report (SUR) showed comparable use of methamphetamine across sites with the individual site means ranging from 59% (site 5) to 80% (site 3). Drug use as measured by urinalysis was greatly reduced at week 13 compared to the baseline measure; the average rate of methamphetamine-free urine samples across all participants in sites at week 13 was 53%. The highest percentage of methamphetamine-free samples was 85% at site 5; the lowest was at site 1 (40%). Addiction severity index (ASI) composite scores at baseline and protocol completion for all participants demonstrated improvement in all categories over time, except for the medical composite score. The largest composite score reduction in baseline-protocol completion was in the drug domain (0.23 versus 0.15). The changes in the ASI scores from baseline to week 13 were consistent across all five sites. Outcomes of the behavioral trial indicated that the MCTG recruited well; collected study data accurately and reliably; and created a vehicle that can assess promising pharmacotherapies for methamphetamine addiction treatment medications. The MCTG strategy appears to be a feasible approach to increase NIDA's capacity to conduct clinical trials to evaluate potential pharmacotherapies for methamphetamine addiction.

Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Greene, Stephen J; Hernandez, Adrian F; Sun, Jie-Lena; Metra, Marco; Butler, Javed; Ambrosy, Andrew P; Ezekowitz, Justin A; Starling, Randall C; Teerlink, John R; Schulte, Phillip J; Voors, Adriaan A; Armstrong, Paul W; O'Connor, Christopher M; Mentz, Robert J

2016-09-01

Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear. We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled ≥1 patient, and median enrollment was 12 patients (interquartile range, 5-23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89-0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01-1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98-1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96-0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98-1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction P<0.01). In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2016 American Heart Association, Inc.

Study of Tranexamic Acid During Air Medical Prehospital Transport Trial (STAAMP trial)

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-2-0080 TITLE: Study of Tranexamic Acid During Air Medical Prehospital Transport Trial (STAAMP trial) PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Study of Tranexamic Acid During Air Medical Prehospital Transport Trial (STAAMP trial) 5b. GRANT NUMBER W81XWH...IRB approval regarding changes to the protocol language. 15. SUBJECT TERMS Prehospital; Tranexamic acid 16. SECURITY CLASSIFICATION OF: 17. LIMITATION

Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

PubMed

Martin, P; Brown, M C; Espin-Garcia, O; Cuffe, S; Pringle, D; Mahler, M; Villeneuve, J; Niu, C; Charow, R; Lam, C; Shani, R M; Hon, H; Otsuka, M; Xu, W; Alibhai, S; Jenkinson, J; Liu, G

2016-03-01

In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format. © 2015 John Wiley & Sons Ltd.

Software for computerised analysis of cardiotocographic traces.

PubMed

Romano, M; Bifulco, P; Ruffo, M; Improta, G; Clemente, F; Cesarelli, M

2016-02-01

Despite the widespread use of cardiotocography in foetal monitoring, the evaluation of foetal status suffers from a considerable inter and intra-observer variability. In order to overcome the main limitations of visual cardiotocographic assessment, computerised methods to analyse cardiotocographic recordings have been recently developed. In this study, a new software for automated analysis of foetal heart rate is presented. It allows an automatic procedure for measuring the most relevant parameters derivable from cardiotocographic traces. Simulated and real cardiotocographic traces were analysed to test software reliability. In artificial traces, we simulated a set number of events (accelerations, decelerations and contractions) to be recognised. In the case of real signals, instead, results of the computerised analysis were compared with the visual assessment performed by 18 expert clinicians and three performance indexes were computed to gain information about performances of the proposed software. The software showed preliminary performance we judged satisfactory in that the results matched completely the requirements, as proved by tests on artificial signals in which all simulated events were detected from the software. Performance indexes computed in comparison with obstetricians' evaluations are, on the contrary, not so satisfactory; in fact they led to obtain the following values of the statistical parameters: sensitivity equal to 93%, positive predictive value equal to 82% and accuracy equal to 77%. Very probably this arises from the high variability of trace annotation carried out by clinicians. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Proposal for the Development of a Standardized Protocol for Assessing the Economic Costs of HIV Prevention Interventions

PubMed Central

Pinkerton, Steven D.; Pearson, Cynthia R.; Eachus, Susan R.; Berg, Karina M.; Grimes, Richard M.

2008-01-01

Summary Maximizing our economic investment in HIV prevention requires balancing the costs of candidate interventions against their effects and selecting the most cost-effective interventions for implementation. However, many HIV prevention intervention trials do not collect cost information, and those that do use a variety of cost data collection methods and analysis techniques. Standardized cost data collection procedures, instrumentation, and analysis techniques are needed to facilitate the task of assessing intervention costs and to ensure comparability across intervention trials. This article describes the basic elements of a standardized cost data collection and analysis protocol and outlines a computer-based approach to implementing this protocol. Ultimately, the development of such a protocol would require contributions and “buy-in” from a diverse range of stakeholders, including HIV prevention researchers, cost-effectiveness analysts, community collaborators, public health decision makers, and funding agencies. PMID:18301128

Effects of different impact exercise modalities on bone mineral density in premenopausal women: a meta-analysis.

PubMed

Martyn-St James, Marrissa; Carroll, Sean

2010-05-01

Our objective was to assess the effects of differing modes of impact exercise on bone density at the hip and spine in premenopausal women through systematic review and meta-analysis. Electronic databases, key journals and reference lists were searched for controlled trials investigating the effects of impact exercise interventions on lumbar spine (LS), femoral neck (FN) and total hip (TH) bone mineral density (BMD) in premenopausal women. Exercise protocols were categorised according to impact loading characteristics. Weighted mean difference (WMD) meta-analyses were undertaken. Heterogeneity amongst trials was assessed. Fixed and random effects models were applied. Inspection of funnel plot symmetry was performed. Trial quality assessment was also undertaken. Combined protocols integrating odd- or high-impact exercise with high-magnitude loading (resistance exercises), were effective in increasing BMD at both LS and FN [WMD (fixed effect) 0.009 g cm(-2) 95% CI (0.002-0.015) and 0.007 g cm(-2) 95% CI (0.001-0.013); P = 0.011 and 0.017, respectively]. High-impact only protocols were effective on femoral neck BMD [WMD (fixed effect) 0.024 g cm(-2) 95% CI (0.002-0.027); P < 0.00001]. Funnel plots showed some asymmetry for positive BMD outcomes. Insufficient numbers of protocols assessing TH BMD were available for assessment. Exercise programmes that combine odd- or high-impact activity with high-magnitude resistance training appear effective in augmenting BMD in premenopausal women at the hip and spine. High-impact-alone protocols are effective only on hip BMD in this group. However, diverse methodological and reporting discrepancies are evident in published trials.

Study protocol for a randomized controlled trial: tongue strengthening exercises in head and neck cancer patients, does exercise load matter?

PubMed

Van Nuffelen, Gwen; Van den Steen, Leen; Vanderveken, Olivier; Specenier, Pol; Van Laer, Carl; Van Rompaey, Diane; Guns, Cindy; Mariën, Steven; Peeters, Marc; Van de Heyning, Paul; Vanderwegen, Jan; De Bodt, Marc

2015-09-04

Reduced tongue strength is an important factor contributing to early and late dysphagia in head and neck cancer patients previously treated with chemoradiotherapy. The evidence is growing that tongue strengthening exercises can improve tongue strength and swallowing function in both healthy and dysphagic subjects. However, little is known about the impact of specific features of an exercise protocol for tongue strength on the actual outcome (strength or swallowing function). Previous research originating in the fields of sports medicine and physical rehabilitation shows that the degree of exercise load is an influential factor for increasing muscle strength in the limb skeletal muscles. Since the tongue is considered a muscular hydrostat, it remains to be proven whether the same concepts will apply. This ongoing randomized controlled trial in chemoradiotherapy-treated patients with head and neck cancer investigates the effect of three tongue strengthening exercise protocols, with different degrees of exercise load, on tongue strength and swallowing. At enrollment, 51 patients whose dysphagia is primarily related to reduced tongue strength are randomly assigned to a training schedule of 60, 80, or 100% of their maximal tongue strength. Patients are treated three times a week for 8 weeks, executing 120 repetitions of the assigned exercise once per training day. Exercise load is progressively adjusted every 2 weeks. Patients are evaluated before, during and after treatment by means of tongue strength measurements, fiber-optic endoscopic evaluation of swallowing and quality-of-life questionnaires. This randomized controlled trial is the first to systematically investigate the effect of different exercise loads in tongue strengthening exercise protocols. The results will allow the development of more efficacious protocols. Current Controlled Trials ISRCTN14447678.

The evaluation of complex clinical trial protocols: resources available to research ethics committees and the use of clinical trial registries--a case study.

PubMed

Homedes, Núria; Ugalde, Antonio

2015-06-01

To assess the potential role of clinical trial (CT) registries and other resources available to research ethics committees (RECs) in the evaluation of complex CT protocols in low-income and middle-income countries. Using a case study approach, the authors examined the decision-making process of a REC in Argentina and its efforts to use available resources to decide on a complex protocol. We also analysed the information in the USA and other CT registries and consulted 24 CT experts in seven countries. Information requested by the Argentinean REC from other national RECs and ethics' experts was not useful to verify the adequacy of the REC's decision whether or not to approve the CT. The responses from the national regulatory agency and the sponsor were not helpful either. The identification of international resources that could assist was beyond the REC's capability. The information in the USA and other CT registries is limited, and at times misleading; and its accuracy is not verified by register keepers. RECs have limited access to experts and institutions that could assist them in their deliberations. Sponsors do not always answer RECs' request for information to properly conduct the ethical and methodological assessment of CT protocols. The usefulness of the CT registries is curtailed by the lack of appropriate codes and by data errors. Information about reasons for rejection, withdrawal or suspension of the trial should be included in the registries. Establishing formal channels of communication among national and foreign RECs and with independent international reference centres could strengthen the ethical review of CT protocols. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases.  CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides comprehensive clinical and administrative support to the National Cancer Institute’s Center for Cancer Research’s (CCR), Office of Regulatory Affairs for protocol development review, regulatory review, and the implementation process as well as oversees medical writing/editing, regulatory/ compliance, and protocol coordination/navigation and administration. KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL The Protocol Coordinator II: Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials Provides deployment of clinical support services for clinical research Streamlines protocol development timeline Provides data and document collection and compilation for regulatory filing with the FDA and other regulatory authorities Provides administrative coordination and general logistical support for regulatory activities Ensures the provision of training for investigators and associate staff to reinforce and enhance a GCP culture Provides quality assurance and quality control oversight Performs regulatory review of clinical protocols, informed consent and other clinical documents Tracks and facilitates a portfolio of protocols through each process step (IRB, RAC, DSMB, Office of Protocol Services) Assists clinical investigators in preparing clinical research protocols, including writing and formatting protocol documents and consent forms Prepares protocol packages for review and ensures that protocol packages include all of the required material and comply with CCR, NCI and NIH policies Collaborates with investigators to resolve any protocol/data issues Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI Institutional Review Board (IRB) and the clinical trial sponsor or the FDA Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events Attends and prepares minutes for the Branch Protocol Review Committees For protocols that are performed with other research centers: contacts coordinators at other centers to obtain review committee approvals at these centers, maintains records of these approvals at the outside centers in the protocol files, and sends protocol amendments and other reports to the participating centers Maintains a schedule of all review committee submission deadline dates and meeting dates Assists clinical investigators in understanding and complying with the entire review process Works closely with the NCI Protocol Review Office in establishing and maintaining a paperless automated document management and tracking system for NCI protocols Converts protocols from Word format to PDF with bookmarks Maintains the PDF version of the most current approved version of each active clinical protocol on a central server    This position has the option to be located in Frederick or Rockville, Maryland.

Support and assessment for fall emergency referrals (SAFER 2) research protocol: cluster randomised trial of the clinical and cost effectiveness of new protocols for emergency ambulance paramedics to assess and refer to appropriate community-based care

PubMed Central

Snooks, Helen; Anthony, Rebecca; Chatters, Robin; Cheung, Wai-Yee; Dale, Jeremy; Donohoe, Rachael; Gaze, Sarah; Halter, Mary; Koniotou, Marina; Logan, Phillippa; Lyons, Ronan; Mason, Suzanne; Nicholl, Jon; Phillips, Ceri; Phillips, Judith; Russell, Ian; Siriwardena, A Niroshan; Wani, Mushtaq; Watkins, Alan; Whitfield, Richard; Wilson, Lynsey

2012-01-01

Introduction Emergency calls to ambulance services are frequent for older people who have fallen, but ambulance crews often leave patients at the scene without ongoing care. Evidence shows that when left at home with no further support older people often experience subsequent falls which result in injury and emergency-department attendances. SAFER 2 is an evaluation of a new clinical protocol which allows paramedics to assess and refer older people who have fallen, and do not need hospital care, to community-based falls services. In this protocol paper, we report methods and progress during trial implementation. SAFER 2 is recruiting patients through three ambulance services. A successful trial will provide robust evidence about the value of this new model of care, and enable ambulance services to use resources efficiently. Design Pragmatic cluster randomised trial. Methods and analysis We randomly allocated 25 participating ambulance stations (clusters) in three services to intervention or control group. Intervention paramedics received training and clinical protocols for assessing and referring older people who have fallen to community-based falls services when appropriate, while control paramedics deliver care as usual. Patients are eligible for the trial if they are aged 65 or over; resident in a participating falls service catchment area; and attended by a trial paramedic following an emergency call coded as a fall without priority symptoms. The principal outcome is the rate of further emergency contacts (or death), for any cause and for falls. Secondary outcomes include further falls, health-related quality of life, ‘fear of falling’, patient satisfaction reported by participants through postal questionnaires at 1 and 6 months, and quality and pathways of care at the index incident. We shall compare National Health Service (NHS) and patient/carer costs between intervention and control groups and estimate quality-adjusted life years (QALYs) gained from the intervention and thus incremental cost per QALY. We shall estimate wider system effects on key-performance indicators. We shall interview 60 intervention patients, and conduct focus groups with contributing NHS staff to explore their experiences of the assessment and referral service. We shall analyse quantitative trial data by ‘treatment allocated’; and qualitative data using content analysis. Ethics and dissemination The Research Ethics Committee for Wales gave ethical approval and each participating centre gave NHS Research and Development approval. We shall disseminate study findings through peer-reviewed publications and conference presentations. Trial Registration: ISRCTN 60481756 PMID:23148348

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

NIDA’s Clinical Trials Network: An Opportunity for HIV Research in Community Substance Abuse Treatment Programs

PubMed Central

Tross, Susan; Campbell, Aimee N. C.; Calsyn, Donald A.; Metsch, Lisa R.; Sorensen, James L.; Shoptaw, Steven; Haynes, Louise; Woody, George E.; Malow, Robert M.; Brown, Lawrence S.; Feaster, Daniel J.; Booth, Robert E.; Mandler, Raul N.; Masson, Carmen; Holmes, Beverly W.; Colfax, Grant; Brooks, Audrey J.; Hien, Denise A.; Schackman, Bruce R.; Korthuis, P. Todd; Miele, Gloria M.

2012-01-01

Background/Objectives HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years. Results While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs. Conclusion/Significance While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed. PMID:21854270

NIDA's Clinical Trials Network: an opportunity for HIV research in community substance abuse treatment programs.

PubMed

Tross, Susan; Campbell, Aimee N C; Calsyn, Donald A; Metsch, Lisa R; Sorensen, James L; Shoptaw, Steven; Haynes, Louise; Woody, George E; Malow, Robert M; Brown, Lawrence S; Feaster, Daniel J; Booth, Robert E; Mandler, Raul N; Masson, Carmen; Holmes, Beverly W; Colfax, Grant; Brooks, Audrey J; Hien, Denise A; Schackman, Bruce R; Korthuis, P Todd; Miele, Gloria M

2011-09-01

HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years. While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs. While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.

Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review.

PubMed

Strojan, Primož; Vermorken, Jan B; Beitler, Jonathan J; Saba, Nabil F; Haigentz, Missak; Bossi, Paolo; Worden, Francis P; Langendijk, Johannes A; Eisbruch, Avraham; Mendenhall, William M; Lee, Anne W M; Harrison, Louis B; Bradford, Carol R; Smee, Robert; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2016-04-01

The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016. © 2015 Wiley Periodicals, Inc.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides comprehensive clinical and administrative support to the National Cancer Institute’s Center for Cancer Research’s (CCR) Protocol Support Office (PSO) for protocol development review, regulatory review, and the implementation process as well as oversees medical writing/editing, regulatory/ compliance, and protocol coordination/navigation and administration. KEY ROLES/RESPONSIBILITIES The Protocol Coordinator III: Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials. Provides deployment of clinical support services for clinical research. Streamlines the protocol development timeline. Provides data and documents collection and compilation for regulatory filing with the U.S. Food and Drug Administration (FDA) and other regulatory authorities.. Provides technical review and report preparation. Provides administrative coordination and general logistical support for regulatory activities. Ensures the provision of training for investigators and associate staff to reinforce and enhance a Good Clinical Practices (GCP) culture. Oversees quality assurance and quality control, performs regulatory review of clinical protocols, informed consent and other clinical documents. Tracks and facilitates a portfolio of protocols through each process step (Institutional Review Board [IRB], Regulatory Affairs Compliance [RAC], Data Safety Monitoring Board [DSMB], Office of Protocol Services). Assists clinical investigators in preparing clinical research protocols, including writing and formatting consent forms. Prepares protocol packages for review and ensures that protocol packages include all of the required material and comply with CCR, NCI and NIH policies. Collaborates with investigators to resolve any protocol/data issues. Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI IRB, and the clinical trial sponsor or the FDA. Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events. Attends and prepares minutes for the Branch Protocol Review Committees. Contacts coordinators at other centers for protocols that are performed there to obtain review committee approvals at those centers, maintains records of these approvals and sends protocol amendments and other reports to the participating centers. Maintains a schedule of all review committee submission deadline dates and meeting dates. Assists clinical investigators in understanding and complying with the entire review process. Works closely with the NCI Protocol Review Office in establishing and maintaining a paperless automated document and tracking system for NCI protocols. Converts protocols from Word format to .pdf with bookmarks. Maintains the .pdf version of the most current approved version of each active clinical protocol on a central server. This position is located in Rockville, Maryland.

Dosimetry and Image Quality in Control Studies in Computerised Tomography Realized to Paediatric Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernandez, M. R.; Gamboa-deBuen, I.; Dies, P.

Computerised tomography (CT) is a favourite method of medical diagnosis. Its use has thus increased rapidly throughout the world, particularly in studies relating to children. However to avoid administering unnecessarily high doses of radiation to paediatric patients it is important to have correct dose reference levels to minimize risk. The research is being developed within the public health sector at the Hospital Infantil de Mexico 'Dr. Federico Gomez.' We measured the entrance surface air kerma (K{sub P}) in paediatric patients, during the radiological studies of control in CT (studies of head, thorax and abdomen). Phantom was used to evaluate imagemore » quality as the tomograph requires a high resolution image in order to operate at its optimum level.« less

SU-F-J-49: IGRT Credentialing in NCTN Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowenstein, J; Molineu, A; Followill, D

Purpose: To make Image Guided Radiation Therapy (IGRT) credentialing a more unified, consistent and efficient process across the entire National Clinical Trial Network (NCTN). Methods: IGRT plays a role in several advanced NCTN trials. Previously an institution had to be IGRT credentialed for each protocol. When institutions were allowed to use previous credentials for new protocols it was limited to the same disease site as the original credentialing. The credentialing was analyzed by the physics PI of the protocol. We consulted with several of these physicists to determine what is important to consider when reviewing submissions and to learn waysmore » to apply credentialing more broadly. Results: For trials open in 2016, IGRT credentialing can be simplified to cover either boney anatomy or soft tissue. This revised credentialing will cover all disease sites based on the type of anatomy, unless otherwise stated within the protocol. Institutions will submit will complete an online questionnaire about their IGRT procedures. Boney anatomy requirements will include submission of data from 2 sequential fraction of both a patient aligned with boney anatomy and pelvic patient. Soft tissue will require similar submissions for a patient aligned using soft tissue and a pelvic patient. Institutions will only be required to submit the pelvic patient once. Data should be in DICOM format and includes planning CT set, RT structure set, RT plan file, RT dose file, localization images and spatial registration file (if available). Reviews will be done by IROC-Houston staff who will continue to provide feedback to the sites. Conclusion: This revised IGRT credentialing process will bring consistency, a savings in time and effort for both the IROC Houston QA office and to those institutions wanting to be credentialed to participate in NCTN Trials. Sponsored by NIH/NCI CA10953.« less

Salivary cortisol and testosterone responses to resistance and plyometric exercise in 12- to 14-year-old boys.

PubMed

Klentrou, Panagiota; Giannopoulou, Angeliki; McKinlay, Brandon J; Wallace, Phillip; Muir, Cameron; Falk, Bareket; Mack, Diane

2016-07-01

This study examined changes in salivary testosterone and cortisol following resistance and plyometric exercise protocols in active boys. In a crossover experimental design, 26 peri-pubertal (12- to 14-year-old) soccer players performed 2 exercise trials in random order, on separate evenings, 1 week apart. Each trial included a 30 min control session followed by 30 min of either resistance or plyometric exercise. Saliva was collected at baseline, post-control (i.e., pre-exercise), and 5 and 30 min post-exercise. There were no significant differences in the baseline hormone concentrations between trials or between weeks (p > 0.05). A significant effect for time was found for testosterone (p = 0.02, [Formula: see text] = 0.14), which increased from pre-exercise to 5 min post-exercise in both the resistance (27% ± 5%) and plyometric (12% ± 6%) protocols. Cortisol decreased to a similar extent in both trials (p = 0.009, [Formula: see text] = 0.19) from baseline to post-control and then to 5 min post-exercise, following its typical circadian decrease in the evening hours. However, a significant protocol-by-time interaction was observed for cortisol, which increased 30 min after the plyometrics (+31% ± 12%) but continued to decrease following the resistance protocol (-21% ± 5%). Our results suggest that in young male athletes, multiple modes of exercise can lead to a transient anabolic state, thus maximizing the beneficial effects on growth and development, when exercise is performed in the evening hours.

Differences in reporting of analyses in internal company documents versus published trial reports: comparisons in industry-sponsored trials in off-label uses of gabapentin.

PubMed

Vedula, S Swaroop; Li, Tianjing; Dickersin, Kay

2013-01-01

Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses). Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded.

Shoulder function and work disability after decompression surgery for subacromial impingement syndrome: a randomised controlled trial of physiotherapy exercises and occupational medical assistance

PubMed Central

2014-01-01

Background Surgery for subacromial impingement syndrome is often performed in working age and postoperative physiotherapy exercises are widely used to help restore function. A recent Danish study showed that 10% of a nationwide cohort of patients retired prematurely within two years after surgery. Few studies have compared effects of different postoperative exercise programmes on shoulder function, and no studies have evaluated workplace-oriented interventions to reduce postoperative work disability. This study aims to evaluate the effectiveness of physiotherapy exercises and occupational medical assistance compared with usual care in improving shoulder function and reducing postoperative work disability after arthroscopic subacromial decompression. Methods/Design The study is a mainly pragmatic multicentre randomised controlled trial. The trial is embedded in a cohort study of shoulder patients referred to public departments of orthopaedic surgery in Central Denmark Region. Patients aged ≥18–≤63 years, who still have shoulder symptoms 8–12 weeks after surgery, constitute the study population. Around 130 participants are allocated to: 1) physiotherapy exercises, 2) occupational medical assistance, 3) physiotherapy exercises and occupational medical assistance, and 4) usual care. Intervention manuals allow individual tailoring. Primary outcome measures include Oxford Shoulder Score and sickness absence due to symptoms from the operated shoulder. Randomisation is computerised with allocation concealment by randomly permuted block sizes. Statistical analyses will primarily be performed according to the intention-to-treat principle. Discussion The paper presents the rationale, design, methods, and operational aspects of the Shoulder Intervention Project (SIP). SIP evaluates a new rehabilitation approach, where physiotherapy and occupational interventions are provided in continuity of surgical episodes of care. If successful, the project may serve as a model for rehabilitation of surgical shoulder patients. Trial registration Current Controlled Trials ISRCTN55768749. PMID:24952581

Chinese herbal medicines for hyperthyroidism.

PubMed

Zen, X X; Yuan, Y; Liu, Y; Wu, T X; Han, S

2007-04-18

Hyperthyroidism is a disease in which excessive amounts of thyroid hormones circulate in the blood. Patients, among other things suffer from tachycardia, warm moist skin and raised body temperature. The treatment of hyperthyroidism includes symptom relief and therapy with antithyroid medications, radioiodine and thyroidectomy. Medicinal herbs are used alone or in combination with antithyroid agents to treat hyperthyroidism in China and some other countries. To assess the effects of Chinese herbal medicines for treating hyperthyroidism. Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library, the Chinese Biomedical Database. Randomised controlled trials comparing the effects of Chinese herbal medicines alone with Chinese herbal medicines combined with antithyroid drugs, radioiodine or both. Three authors interviewed authors of all potentially relevant studies by telephone to verify randomisation procedures. One author entered data into a data extraction form and another author verified the results of this procedure. Thirteen relevant trials with 1770 participants were included. All of them were of low quality. Fifty-two studies still need to be assessed because the original authors could not be interviewed. None of these trials analysed mortality, health related quality of life, economic outcomes or compliance. Compared to antithyroid drugs alone the results showed that Chinese herbal medicines combined with antithyroid drugs may offer benefits in lowering relapse rates, reducing the incidence of adverse effects, relieving symptoms, improving thyroid antibody status and thyroid function. Two trials investigated Chinese herbal medicine versus radioiodine and reported improvements in anxiety, tachycardia and heat intolerance. However, thyroid function - with the exception of restored thyroid stimulating hormone (TSH) - was not significantly altered. The results suggest that traditional Chinese herbal medicines added to other routine treatment have a therapeutic potential for people with hyperthyroidism. However, due to methodological limitations, we could not identify a well-designed trial to provide strong evidence for Chinese traditional herbal medicine in the treatment of hyperthyroidism. Thus, we currently cannot recommend any single preparation or formulation for clinical use.

Assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in pre-diabetics, a randomized, double-blind, multicenter, placebo controlled trial: study protocol for a randomized controlled trial.

PubMed

Crawford, Paul; Thai, Chuong; Obholz, Joshua; Schievenin, Jeffrey; True, Mark; Shah, Sachin A; Hallgren, John; Clark, Jill; Sharon, Danny

2016-01-05

The World Health Organization predicts that by 2030 diabetes will be the seventh leading cause of death in the world. Multiple studies have tried to determine if cinnamon is an effective treatment for diabetes. Cinnamon extract is an insulin sensitizer, protects mesangial cells, decreases inflammatory markers, and lowers glucose, lipids, and blood pressure in patients with type 2 diabetes, so we developed a protocol to study whether ingestion of water-soluble cinnamon extract prevents progression from pre-diabetes to diabetes. This is a randomized, double-blind, placebo-controlled trial comparing cinnamon extract versus placebo in subjects with pre-diabetes who have committed to participate in a lifestyle change program. The trial will be conducted at five sites and will include 428 subjects who take cinnamon extract or placebo for 1 year. Follow-up for these subjects will be for a total of 2 years (nine study visits). The primary outcomes to be assessed are 1) conversion of patients from pre-diabetes to diabetes and 2) impact of water-soluble cinnamon extract on hepatic transaminases, renal function, and QT interval on electrocardiogram. Secondary outcomes include changes in HbA1c, lipids, waist circumference, weight, blood pressure, and fasting plasma glucose. The trial protocol has been approved by the Institutional Review Board of the US Air Force 59th Medical Wing, Wilford Hall Ambulatory Surgical Center (Protocol FWH20110035H). Investigator-sponsored Investigational New Drug status (114078) was granted by the US Food and Drug Administration. This study will provide high-quality evidence of the efficacy of water-soluble cinnamon extract in conjunction with lifestyle intervention for preventing patients with pre-diabetes from converting to diabetes. Additionally, it will provide important safety information about water-soluble cinnamon extract. ClinicalTrials.gov Identifier: NCT01301521 , 18 February 2011.

Virtual reality for treatment compliance for people with serious mental illness.

PubMed

Välimäki, Maritta; Hätönen, Heli M; Lahti, Mari E; Kurki, Marjo; Hottinen, Anja; Metsäranta, Kiki; Riihimäki, Tanja; Adams, Clive E

2014-10-08

Virtual reality (VR) is computerised real-time technology, which can be used an alternative assessment and treatment tool in the mental health field. Virtual reality may take different forms to simulate real-life activities and support treatment. To investigate the effects of virtual reality to support treatment compliance in people with serious mental illness. We searched the Cochrane Schizophrenia Group Trials Register (most recent, 17th September 2013) and relevant reference lists. All relevant randomised studies comparing virtual reality with standard care for those with serious mental illnesses. We defined virtual reality as a computerised real-time technology using graphics, sound and other sensory input, which creates the interactive computer-mediated world as a therapeutic tool. All review authors independently selected studies and extracted data. For homogeneous dichotomous data the risk difference (RD) and the 95% confidence intervals (CI) were calculated on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). We assessed risk of bias and created a 'Summary of findings' table using the GRADE approach. We identified three short-term trials (total of 156 participants, duration five to 12 weeks). Outcomes were prone to at least a moderate risk of overestimating positive effects. We found that virtual reality had little effects regarding compliance (3 RCTs, n = 156, RD loss to follow-up 0.02 CI -0.08 to 0.12, low quality evidence), cognitive functioning (1 RCT, n = 27, MD average score on Cognistat 4.67 CI -1.76 to 11.10, low quality evidence), social skills (1 RCT, n = 64, MD average score on social problem solving SPSI-R (Social Problem Solving Inventory - Revised) -2.30 CI -8.13 to 3.53, low quality evidence), or acceptability of intervention (2 RCTs, n = 92, RD 0.05 CI -0.09 to 0.19, low quality evidence). There were no data reported on mental state, insight, behaviour, quality of life, costs, service utilisation, or adverse effects. Satisfaction with treatment - measured using an un-referenced scale - and reported as "interest in training" was better for the virtual reality group (1 RCT, n = 64, MD 6.00 CI 1.39 to 10.61,low quality evidence). There is no clear good quality evidence for or against using virtual reality for treatment compliance among people with serious mental illness. If virtual reality is used, the experimental nature of the intervention should be clearly explained. High-quality studies should be undertaken in this area to explore any effects of this novel intervention and variations of approach.

Evaluation of a new chest tube removal protocol using digital air leak monitoring after lobectomy: a prospective randomised trial.

PubMed

Brunelli, Alessandro; Salati, Michele; Refai, Majed; Di Nunzio, Luca; Xiumé, Francesco; Sabbatini, Armando

2010-01-01

The objective of this randomised trial was to assess the effectiveness of a new fast-track chest tube removal protocol taking advantage of digital monitoring of air leak compared to a traditional protocol using visual and subjective assessment of air leak (bubbles). One hundred and sixty-six patients submitted to pulmonary lobectomy for lung cancer were randomised in two groups with different chest tube removal protocols: (1) in the new protocol, chest tube was removed based on digitally recorded measurements of air leak flow; (2) in the traditional protocol, the chest tube removal was based on an instantaneous assessment of air leak during daily rounds. The two groups were compared in terms of chest tube duration, hospital stay and costs. The two groups were well matched for several preoperative and operative variables. Compared to the traditional protocol, the new digital recording protocol showed mean reductions in chest tube duration (p=0.0007), hospital stay (p=0.007) of 0.9 day, and a mean cost saving of euro 476 per patient (p=0.008). In the new chest tube removal protocol, 51% of patients had their chest tube removed by the second postoperative day versus only 12% of those in the traditional protocol. The application of a chest tube removal protocol using a digital drainage unit featuring a continuous recording of air leak was safe and cost effective. Although future studies are warranted to confirm these results in other settings, the use of this new protocol is now routinely applied in our practice. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

PubMed

Riber-Hansen, Rikke; Hastrup, Nina; Clemmensen, Ole; Behrendt, Nille; Klausen, Siri; Ramsing, Mette; Spaun, Eva; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

2012-02-01

Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50μm apart (EORTC Protocol) followed by complete 250μm step-sectioning. Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

PubMed

Green, Robert C; Christensen, Kurt D; Cupples, L Adrienne; Relkin, Norman R; Whitehouse, Peter J; Royal, Charmaine D M; Obisesan, Thomas O; Cook-Deegan, Robert; Linnenbringer, Erin; Butson, Melissa Barber; Fasaye, Grace-Ann; Levinson, Elana; Roberts, J Scott

2015-10-01

Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

A commentary on Adolf Eichmann's Rorschach.

PubMed

McCully, R S

1980-06-01

A Rorschach was administered to Adolf Eichmann in Jerusalem in 1961 at the time of his trial for war crimes. The recent publication of this protocol offers an opportunity to compare his personal world against opinions formed about him by observers at his trial. Various professionals certified Eichmann as a banal, ordinary man, and a societal theory was proposed about Nazism based in part on impressions of Eichmann as an uncomplicated man. This commentary examines Eichmann's protocol and provides an opinion that in several important respects his record includes features uncharacteristic of an ordinary, banal mind.

P-value interpretation and alpha allocation in clinical trials.

PubMed

Moyé, L A

1998-08-01

Although much value has been placed on type I error event probabilities in clinical trials, interpretive difficulties often arise that are directly related to clinical trial complexity. Deviations of the trial execution from its protocol, the presence of multiple treatment arms, and the inclusion of multiple end points complicate the interpretation of an experiment's reported alpha level. The purpose of this manuscript is to formulate the discussion of P values (and power for studies showing no significant differences) on the basis of the event whose relative frequency they represent. Experimental discordance (discrepancies between the protocol's directives and the experiment's execution) is linked to difficulty in alpha and beta interpretation. Mild experimental discordance leads to an acceptable adjustment for alpha or beta, while severe discordance results in their corruption. Finally, guidelines are provided for allocating type I error among a collection of end points in a prospectively designed, randomized controlled clinical trial. When considering secondary end point inclusion in clinical trials, investigators should increase the sample size to preserve the type I error rates at acceptable levels.

Using mobile technology to deliver a cognitive behaviour therapy-informed intervention in early psychosis (Actissist): study protocol for a randomised controlled trial.

PubMed

Bucci, Sandra; Barrowclough, Christine; Ainsworth, John; Morris, Rohan; Berry, Katherine; Machin, Matthew; Emsley, Richard; Lewis, Shon; Edge, Dawn; Buchan, Iain; Haddock, Gillian

2015-09-10

Cognitive behaviour therapy (CBT) is recommended for the treatment of psychosis; however, only a small proportion of service users have access to this intervention. Smartphone technology using software applications (apps) could increase access to psychological approaches for psychosis. This paper reports the protocol development for a clinical trial of smartphone-based CBT. We present a study protocol that describes a single-blind randomised controlled trial comparing a cognitive behaviour therapy-informed software application (Actissist) plus Treatment As Usual (TAU) with a symptom monitoring software application (ClinTouch) plus TAU in early psychosis. The study consists of a 12-week intervention period. We aim to recruit and randomly assign 36 participants registered with early intervention services (EIS) across the North West of England, UK in a 2:1 ratio to each arm of the trial. Our primary objective is to determine whether in people with early psychosis the Actissist app is feasible to deliver and acceptable to use. Secondary aims are to determine whether Actissist impacts on predictors of first episode psychosis (FEP) relapse and enhances user empowerment, functioning and quality of life. Assessments will take place at baseline, 12 weeks (post-treatment) and 22-weeks (10 weeks post-treatment) by assessors blind to treatment condition. The trial will report on the feasibility and acceptability of Actissist and compare outcomes between the randomised arms. The study also incorporates semi-structured interviews about the experience of participating in the Actissist trial that will be qualitatively analysed to inform future developments of the Actissist protocol and app. To our knowledge, this is the first controlled trial to test the feasibility, acceptability, uptake, attrition and potential efficacy of a CBT-informed smartphone app for early psychosis. Mobile applications designed to deliver a psychologically-informed intervention offer new possibilities to extend the reach of traditional mental health service delivery across a range of serious mental health problems and provide choice about available care. ISRCTN34966555. Date of first registration: 12 June 2014.

South African Research Ethics Committee Review of Standards of Prevention in HIV Vaccine Trial Protocols.

PubMed

Essack, Zaynab; Wassenaar, Douglas R

2018-04-01

HIV prevention trials provide a prevention package to participants to help prevent HIV acquisition. As new prevention methods are proven effective, this raises ethical and scientific design complexities regarding the prevention package or standard of prevention. Given its high HIV incidence and prevalence, South Africa has become a hub for HIV prevention research. For this reason, it is critical to study the implementation of relevant ethical-legal frameworks for such research in South Africa. This qualitative study used in-depth interviews to explore the practices and perspectives of eight members of South African research ethics committees (RECs) who have reviewed protocols for HIV vaccine trials. Their practices and perspectives are compared with ethics guideline requirements for standards of prevention.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis.

PubMed

Tierney, Jayne F; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L; Burdett, Sarah

2015-11-01

To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis

PubMed Central

Tierney, Jayne F.; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L.; Burdett, Sarah; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B.W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J.P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

2015-01-01

Objectives To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Study Design and Setting Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. Results We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. Conclusions IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. PMID:26186982

Resource use and costs of type 2 diabetes patients receiving managed or protocolized primary care: a controlled clinical trial

PubMed Central

2014-01-01

Background The increasing prevalence of diabetes is associated with increased health care use and costs. Innovations to improve the quality of care, manage the increasing demand for health care and control the growth of health care costs are needed. The aim of this study is to evaluate the care process and costs of managed, protocolized and usual care for type 2 diabetes patients from a societal perspective. Methods In two distinct regions of the Netherlands, both managed and protocolized diabetes care were implemented. Managed care was characterized by centralized organization, coordination, responsibility and centralized annual assessment. Protocolized care had a partly centralized organizational structure. Usual care was characterized by a decentralized organizational structure. Using a quasi-experimental control group pretest-posttest design, the care process (guideline adherence) and costs were compared between managed (n = 253), protocolized (n = 197), and usual care (n = 333). We made a distinction between direct health care costs, direct non-health care costs and indirect costs. Multivariate regression models were used to estimate differences in costs adjusted for confounding factors. Because of the skewed distribution of the costs, bootstrapping methods (5000 replications) with a bias-corrected and accelerated approach were used to estimate 95% confidence intervals (CI) around the differences in costs. Results Compared to usual and protocolized care, in managed care more patients were treated according to diabetes guidelines. Secondary health care use was higher in patients under usual care compared to managed and protocolized care. Compared to usual care, direct costs were significantly lower in managed care (€-1.181 (95% CI: -2.597 to -334)) while indirect costs were higher (€758 (95% CI: -353 to 2.701), although not significant. Direct, indirect and total costs were lower in protocolized care compared to usual care (though not significantly). Conclusions Compared to usual care, managed care was significantly associated with better process in terms of diabetes care, fewer secondary care consultations and lower health care costs. The same trends were seen for protocolized care, however they were not statistically significant. Trial registration Current Controlled trials: ISRCTN66124817. PMID:24966055

Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

PubMed

Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

2014-10-29

Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Wang, Shengjun; Jiang, Hongli; Yu, Qin; She, Bin; Mao, Bing

2017-01-05

The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care

PubMed Central

Kraybill, Ashley; Dember, Laura M.; Joffe, Steven; Karlawish, Jason; Ellenberg, Susan S.; Madden, Vanessa; Halpern, Scott D.

2016-01-01

Background Pragmatic trials comparing standard-of-care interventions may improve the quality of care for future patients, but raise ethical questions about limitations on decisional autonomy. We sought to understand how patients and physicians view and respond to these questions in the contexts of pragmatic trials and of usual clinical care. Methods We conducted scenario-based, semi-structured interviews with 32 patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis in outpatient dialysis units and with 24 nephrologists. Each participant was presented with two hypothetical scenarios in which a protocolized approach to hemodialysis treatment time was adopted for the entire dialysis unit as part of a clinical trial or a new clinical practice. Results A modified grounded theory analysis revealed three major themes: 1) the value of research, 2) the effect of protocolized care on patient and physician autonomy, and 3) information exchange between patients and physicians, including the mechanism of consent. Most patients and physicians were willing to relinquish decisional autonomy and were more willing to relinquish autonomy for research purposes than in clinical care. Patients’ concerns towards clinical trials were tempered by their desires for certainty for a positive outcome and for physician validation. Patients tended to believe that being informed about research was more important than the actual mechanism of consent, and most were content with being able to opt out from participating. Conclusions This qualitative study suggests the general acceptability of a pragmatic clinical trial comparing standard-of-care interventions that limits decisional autonomy for nephrologists and patients receiving hemodialysis. Future studies are needed to determine whether similar findings would emerge among other patients and providers considering other standard-of-care trials. PMID:27833931

Standard care versus protocol based therapy for new onset Pseudomonas aeruginosa in cystic fibrosis.

PubMed

Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Treggiari, Miriam M; Konstan, Michael W; Retsch-Bogart, George; Morgan, Wayne; Wagener, Jeff; Gibson, Ronald L; Khan, Umer; Emerson, Julia; Thompson, Valeria; Elkin, Eric P; Ramsey, Bonnie W

2013-10-01

The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15-month time period. As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, P < 0.001). No significant differences in the incidence of hospitalization were observed between cohorts. Protocol-based antimicrobial therapy for newly acquired Pa resulted in a lower rate of Pa recurrence but comparable hospitalization rates as compared to a historical control cohort less aggressively treated with antibiotics for new onset Pa. © 2013 Wiley Periodicals, Inc.

Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care.

PubMed

Kraybill, Ashley; Dember, Laura M; Joffe, Steven; Karlawish, Jason; Ellenberg, Susan S; Madden, Vanessa; Halpern, Scott D

2016-01-01

Pragmatic trials comparing standard-of-care interventions may improve the quality of care for future patients, but raise ethical questions about limitations on decisional autonomy. We sought to understand how patients and physicians view and respond to these questions in the contexts of pragmatic trials and of usual clinical care. We conducted scenario-based, semi-structured interviews with 32 patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis in outpatient dialysis units and with 24 nephrologists. Each participant was presented with two hypothetical scenarios in which a protocolized approach to hemodialysis treatment time was adopted for the entire dialysis unit as part of a clinical trial or a new clinical practice. A modified grounded theory analysis revealed three major themes: 1) the value of research, 2) the effect of protocolized care on patient and physician autonomy, and 3) information exchange between patients and physicians, including the mechanism of consent. Most patients and physicians were willing to relinquish decisional autonomy and were more willing to relinquish autonomy for research purposes than in clinical care. Patients' concerns towards clinical trials were tempered by their desires for certainty for a positive outcome and for physician validation. Patients tended to believe that being informed about research was more important than the actual mechanism of consent, and most were content with being able to opt out from participating. This qualitative study suggests the general acceptability of a pragmatic clinical trial comparing standard-of-care interventions that limits decisional autonomy for nephrologists and patients receiving hemodialysis. Future studies are needed to determine whether similar findings would emerge among other patients and providers considering other standard-of-care trials.

Standard Care versus Protocol Based Therapy for New Onset Pseudomonas aeruginosa in Cystic Fibrosis

PubMed Central

Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Treggiari, Miriam M.; Konstan, Michael W.; Retsch-Bogart, George; Morgan, Wayne; Wagener, Jeff; Gibson, Ronald L.; Khan, Umer; Emerson, Julia; Thompson, Valeria; Elkin, Eric P.; Ramsey, Bonnie W.

2014-01-01

Rationale The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. Methods Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15-month time period. Results As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, p<0.001). No significant differences in the incidence of hospitalization were observed between cohorts. Conclusions Protocol-based antimicrobial therapy for newly acquired Pa resulted in a lower rate of Pa recurrence but comparable hospitalization rates as compared to a historical control cohort less aggressively treated with antibiotics for new onset Pa. PMID:23818295

Is a controlled randomised trial the non-plus-ultra design? A contribution to discussion on comparative, controlled, non-randomised trials.

PubMed

Gaus, Wilhelm; Muche, Rainer

2013-05-01

Clinical studies provide formalised experience for evidence-based medicine (EBM). Many people consider a controlled randomised trial (CRT, identical to a randomised controlled trial RCT) to be the non-plus-ultra design. However, CRTs also have limitations. The problem is not randomisation itself but informed consent for randomisation and masking of therapies according to today's legal and ethical standards. We do not want to de-rate CRTs, but we would like to contribute to the discussion on clinical research methodology. Informed consent to a CRT and masking of therapies plainly select patients. The excellent internal validity of CRTs can be counterbalanced by poor external validity, because internal and external validity act as antagonists. In a CRT, patients may feel like guinea pigs, this can decrease compliance, cause protocol violations, reduce self-healing properties, suppress unspecific therapeutic effects and possibly even modify specific efficacy. A control group (comparative study) is most important for the degree of evidence achieved by a trial. Study control by detailed protocol and good clinical practice (controlled study) is second in importance and randomisation and masking is third (thus the sequence CRT instead of RCT). Controlled non-randomised trials are just as ambitious and detailed as CRTs. We recommend clinicians and biometricians to take high quality controlled non-randomised trials into consideration more often. They combine good internal and external validity, better suit daily medical practice, show better patient compliance and fewer protocol violations, deliver estimators unbiased by alienated patients, and perhaps provide a clearer explanation of the achieved success. Copyright © 2013 Elsevier Inc. All rights reserved.

Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.

PubMed

Allen, Carl E; Laetsch, Theodore W; Mody, Rajen; Irwin, Meredith S; Lim, Megan S; Adamson, Peter C; Seibel, Nita L; Parsons, D Williams; Cho, Y Jae; Janeway, Katherine

2017-05-01

Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies. The Children's Oncology Group (COG), in partnership with the National Cancer Institute (NCI), is planning a trial entitled the COG-NCI Pediatric Molecular Analysis for Therapeutic Choice (Pediatric MATCH) protocol utilizing an umbrella design. This protocol will have centralized infrastructure and will consist of a biomarker profiling protocol and multiple single-arm phase II trials of targeted therapies. Pediatric patients with recurrent or refractory solid tumors, lymphomas, or histiocytoses with measurable disease will be eligible. The Pediatric MATCH Target and Agent Prioritization (TAP) committee includes membership representing COG disease committees, the Food and Drug Administration, and the NCI. The TAP Committee systematically reviewed target and agent pairs for inclusion in the Pediatric MATCH trial. Fifteen drug-target pairs were reviewed by the TAP Committee, with seven recommended for further development as initial arms of the Pediatric MATCH trial. The current evidence for availability, efficacy, and safety of targeted agents in children for each class of mutation considered for inclusion in the Pediatric MATCH trial is discussed in this review. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Patients' perspective and economic variables as objectives in clinical trials: added value to clinical parameters].

PubMed

Bovaira-García, M J; Soler-Company, E

2012-01-01

Patient-reported outcome (PRO) measures complement traditional biomedical outcome measures. The purpose of this study was to evaluate the use of PRO measures including health-related quality of life (HRQoL) questionnaires as a measurement of efficacy and the frequency of inclusion of economic variables related to direct and indirect costs in the design of clinical trials and phase IV observational studies. Moreover, for the trials quality score were measured, and if there were any relationship between the quality study design score and the PRO inclusion. Retrospective observational study of the clinical trials and phase IV observational studies approved by a Clinical Research Ethics Committee (2008-2010). We gathered data concerning general aspects including medical specialty, pathology, methodological quality based on Jadad scale (0-5), inclusion of PRO and economic variables. For clinical trials including HRQoL measurements, we analysed the type of questionnaire in use. Where there were no HRQoL measurements, we analysed if their inclusion would have been proper or not. A total of 70 protocols (59 CTs and 11 phase IV observational studies) were analysed; 37 (52.8%) included PRO measures, and 3 protocols (4.3%) used them as a primary endpoint. Data analysis by therapeutic area showed that PRO measures were most commonly studied in the fields of endocrinology, neurology, digestive diseases, and cardiology. The average quality score for the trials was 2.8. The trials with more PRO inclusion in their end points had a significantly higher quality score. Only 13 (22%) clinical trials and 2 (18.2%) phase IV observational studies included economic variables. The emergence of economic variables in clinical trials and phase IV observational studies evaluated was low, however, more than half of the revised protocols have included PRO measures, reflecting the importance of these parameters in the assessment of the effectiveness of drug treatments, although its use is still not systematic. Copyright © 2011 SECA. Published by Elsevier Espana. All rights reserved.

Jail-to-community treatment continuum for adults with co-occurring substance use and mental disorders: study protocol for a pilot randomized controlled trial.

PubMed

Van Dorn, Richard A; Desmarais, Sarah L; Rade, Candalyn B; Burris, Elizabeth N; Cuddeback, Gary S; Johnson, Kiersten L; Tueller, Stephen J; Comfort, Megan L; Mueser, Kim T

2017-08-04

Adults with co-occurring mental and substance use disorders (CODs) are overrepresented in jails. In-custody barriers to treatment, including a lack of evidence-based treatment options and the often short periods of incarceration, and limited communication between jails and community-based treatment agencies that can hinder immediate enrollment into community care once released have contributed to a cycle of limited treatment engagement, unaddressed criminogenic risks, and (re)arrest among this vulnerable and high-risk population. This paper describes a study that will develop research and communication protocols and adapt two evidence-based treatments, dual-diagnosis motivational interviewing (DDMI) and integrated group therapy (IGT), for delivery to adults with CODs across a jail-to-community treatment continuum. Adaptations to DDMI and IGT were guided by the Risk-Need-Responsivity model and the National Institute of Corrections' implementation competencies; the development of the implementation framework and communication protocols were guided by the Evidence-Based Interagency Implementation Model for community corrections and the Inter-organizational Relationship model, respectively. Implementation and evaluation of the protocols and adapted interventions will occur via an open trial and a pilot randomized trial. The clinical intervention consists of two in-jail DDMI sessions and 12 in-community IGT sessions. Twelve adults with CODs and four clinicians will participate in the open trial to evaluate the acceptability and feasibility of, and fidelity to, the interventions and research and communication protocols. The pilot controlled trial will be conducted with 60 inmates who will be randomized to either DDMI-IGT or treatment as usual. A baseline assessment will be conducted in jail, and four community-based assessments will be conducted during a 6-month follow-up period. Implementation, clinical, public health, and treatment preference outcomes will be evaluated. Findings have the potential to improve both jail- and community-based treatment services for adults with CODs as well as inform methods for conducting rigorous pilot implementation and evaluation research in correctional settings and as inmates re-enter the community. Findings will contribute to a growing area of work focused on interrupting the cycle of limited treatment engagement, unaddressed criminogenic risks, and (re)arrest among adults with CODs. ClinicalTrials.gov, NCT02214667 . Registered on 10 August 2014.

Rehabilitation for the management of knee osteoarthritis using comprehensive traditional Chinese medicine in community health centers: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background It is becoming increasingly necessary for community health centers to make rehabilitation services available to patients with osteoarthritis of the knee. However, for a number of reasons, including a lack of expertise, the small size of community health centers and the availability of only simple medical equipment, conventional rehabilitation therapy has not been widely used in China. Consequently, most patients with knee osteoarthritis seek treatment in high-grade hospitals. However, many patients cannot manage the techniques that they were taught in the hospital. Methods such as acupuncture, tuina, Chinese medical herb fumigation-washing and t’ai chi are easy to do and have been reported to have curative effects in those with knee osteoarthritis. To date, there have been no randomized controlled trials validating comprehensive traditional Chinese medicine for the rehabilitation of knee osteoarthritis in a community health center. Furthermore, there is no standard rehabilitation protocol using traditional Chinese medicine for knee osteoarthritis. The aim of the current study is to develop a comprehensive rehabilitation protocol using traditional Chinese medicine for the management of knee osteoarthritis in a community health center. Method/design This will be a randomized controlled clinical trial with blinded assessment. There will be a 4-week intervention utilizing rehabilitation protocols from traditional Chinese medicine and conventional therapy. Follow-up will be conducted for a period of 12 weeks. A total of 722 participants with knee osteoarthritis will be recruited. Participants will be randomly divided into two groups: experimental and control. Primary outcomes will include range of motion, girth measurement, the visual analogue scale, and results from the manual muscle, six-minute walking and stair-climbing tests. Secondary outcomes will include average daily consumption of pain medication, ability to perform daily tasks and health-related quality-of-life assessments. Other outcomes will include rate of adverse events and economic effects. Relative cost-effectiveness will be determined from health service usage and outcome data. Discussion The primary aim of this trial is to develop a standard protocol for traditional Chinese medicine, which can be adopted by community health centers in China and worldwide, for the rehabilitation of patients with knee osteoarthritis. Trial registration Clinical Trials Registration: ChiCTR-TRC-12002538 PMID:24188276

Automatic control of pressure support for ventilator weaning in surgical intensive care patients.

PubMed

Schädler, Dirk; Engel, Christoph; Elke, Gunnar; Pulletz, Sven; Haake, Nils; Frerichs, Inéz; Zick, Günther; Scholz, Jens; Weiler, Norbert

2012-03-15

Despite its ability to reduce overall ventilation time, protocol-guided weaning from mechanical ventilation is not routinely used in daily clinical practice. Clinical implementation of weaning protocols could be facilitated by integration of knowledge-based, closed-loop controlled protocols into respirators. To determine whether automated weaning decreases overall ventilation time compared with weaning based on a standardized written protocol in an unselected surgical patient population. In this prospective controlled trial patients ventilated for longer than 9 hours were randomly allocated to receive either weaning with automatic control of pressure support ventilation (automated-weaning group) or weaning based on a standardized written protocol (control group) using the same ventilation mode. The primary end point of the study was overall ventilation time. Overall ventilation time (median [25th and 75th percentile]) did not significantly differ between the automated-weaning (31 [19-101] h; n = 150) and control groups (39 [20-118] h; n = 150; P = 0.178). Patients who underwent cardiac surgery (n = 132) exhibited significantly shorter overall ventilation times in the automated-weaning (24 [18-57] h) than in the control group (35 [20-93] h; P = 0.035). The automated-weaning group exhibited shorter ventilation times until the first spontaneous breathing trial (1 [0-15] vs. 9 [1-51] h; P = 0.001) and a trend toward fewer tracheostomies (17 vs. 28; P = 0.075). Overall ventilation times did not significantly differ between weaning using automatic control of pressure support ventilation and weaning based on a standardized written protocol. Patients after cardiac surgery may benefit from automated weaning. Implementation of additional control variables besides the level of pressure support may further improve automated-weaning systems. Clinical trial registered with www.clinicaltrials.gov (NCT 00445289).

Evaluating Data Abstraction Assistant, a novel software application for data abstraction during systematic reviews: protocol for a randomized controlled trial.

PubMed

Saldanha, Ian J; Schmid, Christopher H; Lau, Joseph; Dickersin, Kay; Berlin, Jesse A; Jap, Jens; Smith, Bryant T; Carini, Simona; Chan, Wiley; De Bruijn, Berry; Wallace, Byron C; Hutfless, Susan M; Sim, Ida; Murad, M Hassan; Walsh, Sandra A; Whamond, Elizabeth J; Li, Tianjing

2016-11-22

Data abstraction, a critical systematic review step, is time-consuming and prone to errors. Current standards for approaches to data abstraction rest on a weak evidence base. We developed the Data Abstraction Assistant (DAA), a novel software application designed to facilitate the abstraction process by allowing users to (1) view study article PDFs juxtaposed to electronic data abstraction forms linked to a data abstraction system, (2) highlight (or "pin") the location of the text in the PDF, and (3) copy relevant text from the PDF into the form. We describe the design of a randomized controlled trial (RCT) that compares the relative effectiveness of (A) DAA-facilitated single abstraction plus verification by a second person, (B) traditional (non-DAA-facilitated) single abstraction plus verification by a second person, and (C) traditional independent dual abstraction plus adjudication to ascertain the accuracy and efficiency of abstraction. This is an online, randomized, three-arm, crossover trial. We will enroll 24 pairs of abstractors (i.e., sample size is 48 participants), each pair comprising one less and one more experienced abstractor. Pairs will be randomized to abstract data from six articles, two under each of the three approaches. Abstractors will complete pre-tested data abstraction forms using the Systematic Review Data Repository (SRDR), an online data abstraction system. The primary outcomes are (1) proportion of data items abstracted that constitute an error (compared with an answer key) and (2) total time taken to complete abstraction (by two abstractors in the pair, including verification and/or adjudication). The DAA trial uses a practical design to test a novel software application as a tool to help improve the accuracy and efficiency of the data abstraction process during systematic reviews. Findings from the DAA trial will provide much-needed evidence to strengthen current recommendations for data abstraction approaches. The trial is registered at National Information Center on Health Services Research and Health Care Technology (NICHSR) under Registration # HSRP20152269: https://wwwcf.nlm.nih.gov/hsr_project/view_hsrproj_record.cfm?NLMUNIQUE_ID=20152269&SEARCH_FOR=Tianjing%20Li . All items from the World Health Organization Trial Registration Data Set are covered at various locations in this protocol. Protocol version and date: This is version 2.0 of the protocol, dated September 6, 2016. As needed, we will communicate any protocol amendments to the Institutional Review Boards (IRBs) of Johns Hopkins Bloomberg School of Public Health (JHBSPH) and Brown University. We also will make appropriate as-needed modifications to the NICHSR website in a timely fashion.

Investigating a computerised test of the Stroop effect extended by inclusion of a third, more difficult task.

PubMed

Federmann, Rolf; Goldsmith, Robert; Bäckström, Martin

2007-04-01

A validation study of a computerised test recently developed involving the Stroop effect, extended here by inclusion of a third, more difficult test series, is presented. Three groups of men belonging to the Swedish armed forces and adjudged to differ in their qualifications (20, 32, and 19 men of levels 1, 2, and 3, respectively) and a fourth group of 18 men convicted of serious crimes of violence were given this test, termed the Stress Strategy Test. Discriminant analysis of the test's 12 variables (four for each of the three test series) yielded a discriminant power of 65% for the total group, highest for the level 1 group (80%) and for the nonmilitary group (72%), results substantially better than obtained for the original version of the test with use of similar subject groups.

Modelling the costs and outcomes of changing rates of screening for alcohol misuse by GPs in the Australian context.

PubMed

Shanahan, Marian; Shakeshaft, Anthony; Mattick, Richard P

2006-01-01

To assess the relative cost effectiveness of four strategies (academic detailing, computerised reminder systems, target payments and interactive continuing medical education) to increase the provision of screening and brief interventions by Australian GPs with the ultimate goal of decreasing risky alcohol consumption among their patients. This project used a modelling approach to combine information on the effectiveness and costs of four separate strategies to change GP behaviours to estimate their relative cost effectiveness. The computerised reminder system and academic detailing appear most effective in achieving a decrease in the number of standard drinks consumed by risky drinkers. Regardless of the assumptions made, the targeted payment strategy appeared to be the least cost-effective method to achieve a decrease in risky alcohol consumption while the other three strategies appear reasonably comparable.

Designing healthcare information technology to catalyse change in clinical care.

PubMed

Lester, William T; Zai, Adrian H; Grant, Richard W; Chueh, Henry C

2008-01-01

The gap between best practice and actual patient care continues to be a pervasive problem in our healthcare system. Efforts to improve on this knowledge-performance gap have included computerised disease management programs designed to improve guideline adherence. However, current computerised reminder and decision support interventions directed at changing physician behaviour have had only a limited and variable effect on clinical outcomes. Further, immediate pay-for-performance financial pressures on institutions have created an environment where disease management systems are often created under duress, appended to existing clinical systems and poorly integrated into the existing workflow, potentially limiting their real-world effectiveness. The authors present a review of disease management as well as a conceptual framework to guide the development of more effective health information technology (HIT) tools for translating clinical information into clinical action.

An Australian case study of patient attitudes towards the use of computerised medical records and unique identifiers.

PubMed

Bomba, D; de Silva, A

2001-01-01

Research into patient attitudes towards the use of technology in health care needs to be given much greater attention within health informatics. Past research has often focused more on the needs of health care providers rather than the end users. This article attempts to redress this knowledge bias by reporting on a case study of the responses gained from patients in a selected Australian medical practice towards the use of computerised medical records and unique identifiers. The responses (n=138) were gained from a survey of patients over a 13 day period of practice operation. This case study serves as an example of the type of future consumer health informatics research which can be undertaken not just in Australia but also in other countries, both at local regional levels and at a national level.

Pain Assessment–Can it be Done with a Computerised System? A Systematic Review and Meta-Analysis

PubMed Central

Pombo, Nuno; Garcia, Nuno; Bousson, Kouamana; Spinsante, Susanna; Chorbev, Ivan

2016-01-01

Background: Mobile and web technologies are becoming increasingly used to support the treatment of chronic pain conditions. However, the subjectivity of pain perception makes its management and evaluation very difficult. Pain treatment requires a multi-dimensional approach (e.g., sensory, affective, cognitive) whence the evidence of technology effects across dimensions is lacking. This study aims to describe computerised monitoring systems and to suggest a methodology, based on statistical analysis, to evaluate their effects on pain assessment. Methods: We conducted a review of the English-language literature about computerised systems related to chronic pain complaints that included data collected via mobile devices or Internet, published since 2000 in three relevant bibliographical databases such as BioMed Central, PubMed Central and ScienceDirect. The extracted data include: objective and duration of the study, age and condition of the participants, and type of collected information (e.g., questionnaires, scales). Results: Sixty-two studies were included, encompassing 13,338 participants. A total of 50 (81%) studies related to mobile systems, and 12 (19%) related to web-based systems. Technology and pen-and-paper approaches presented equivalent outcomes related with pain intensity. Conclusions: The adoption of technology was revealed as accurate and feasible as pen-and-paper methods. The proposed assessment model based on data fusion combined with a qualitative assessment method was revealed to be suitable. Data integration raises several concerns and challenges to the design, development and application of monitoring systems applied to pain. PMID:27089351

Virtual classroom helps medical education for both Chinese and foreign students.

PubMed

Shi, C; Wang, L; Li, X; Chai, S; Niu, W; Kong, Y; Zhou, W; Yin, W

2015-11-01

The rapid development of computer and internet technology has a strong influence over one's quality of education within different fields of study. To determine the potential benefits of introducing internet into medical school classes, a pilot study was conducted in three different Chinese medical schools. Seven hundred and eight medical school undergraduates, 385 dental school students and 366 foreign students were randomly recruited to complete a self-administered questionnaire. The contents included personal information, current usage of computer and internet, and attitudes towards the computerised teaching methods. Two forum groups were created using instant message software and were randomly assigned to two classes, allowing students to freely ask or discuss questions with the help of their teachers in these two virtual classrooms. All 1539 questionnaires were accepted and analysed. Although there were some differences between Chinese and foreign undergraduates, both group of students were highly proficient in internet usage and navigation. Overwhelmingly, 88.37% of the students owned a computer and frequently logged onto the internet. Most of them believed that the internet is a helpful adjunct to their studies and held positive attitudes towards computerised teaching. Compared to the classes that were not assigned internet forums, the two experimental classes performed significantly better on the examination. Our results suggest that computerised teaching methods have significant potential to assist in learning for both Chinese and foreign medical undergraduates. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A quality assurance audit: phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01).

PubMed

Steigler, A; Mameghan, H; Lamb, D; Joseph, D; Matthews, J; Franklin, I; Turner, S; Spry, N; Poulsen, M; North, J; Kovacev, O; Denham, J

2000-02-01

In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Surgeon Training, Protocol Compliance, and Technical Outcomes From Breast Cancer Sentinel Lymph Node Randomized Trial

PubMed Central

Ashikaga, Takamaru; Harlow, Seth P.; Skelly, Joan M.; Julian, Thomas B.; Brown, Ann M.; Weaver, Donald L.; Wolmark, Norman

2009-01-01

Background The National Surgical Adjuvant Breast and Bowel Project B-32 trial was designed to determine whether sentinel lymph node resection can achieve the same therapeutic outcomes as axillary lymph node resection but with fewer side effects and is one of the most carefully controlled and monitored randomized trials in the field of surgical oncology. We evaluated the relationship of surgeon trial preparation, protocol compliance audit, and technical outcomes. Methods Preparation for this trial included a protocol manual, a site visit with key participants, an intraoperative session with the surgeon, and prerandomization documentation of protocol compliance. Training categories included surgeons who submitted material on five prerandomization surgeries and were trained by a core trainer (category 1) or by a site trainer (category 2). An expedited group (category 3) included surgeons with extensive experience who submitted material on one prerandomization surgery. At completion of training, surgeons could accrue patients. Two hundred twenty-four surgeons enrolled 4994 patients with breast cancer and were audited for 94 specific items in the following four categories: procedural, operative note, pathology report, and data entry. The relationship of training method; protocol compliance performance audit; and the technical outcomes of the sentinel lymph node resection rate, false-negative rate, and number of sentinel lymph nodes removed was determined. All statistical tests were two-sided. Results The overall sentinel lymph node resection success rate was 96.9% (95% confidence interval [CI] = 96.4% to 97.4%), and the overall false-negative rate was 9.5% (95% CI = 7.4% to 12.0%), with no statistical differences between training methods. Overall audit outcomes were excellent in all four categories. For all three training groups combined, a statistically significant positive association was observed between surgeons’ average number of procedural errors and their false-negative rate (ρ = +0.188, P = .021). Conclusions All three training methods resulted in uniform and high overall sentinel lymph node resection rates. Subgroup analyses identified some variation in false-negative rates that were related to audited outcome performance measures. PMID:19704072

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

(abstract) Experimental Results From Internetworking Data Applications Over Various Wireless Networks Using a Single Flexible Error Control Protocol

NASA Technical Reports Server (NTRS)

Kanai, T.; Kramer, M.; McAuley, A. J.; Nowack, S.; Pinck, D. S.; Ramirez, G.; Stewart, I.; Tohme, H.; Tong, L.

1995-01-01

This paper describes results from several wireless field trials in New Jersey, California, and Colorado, conducted jointly by researchers at Bellcore, JPL, and US West over the course of 1993 and 1994. During these trials, applications communicated over multiple wireless networks including satellite, low power PCS, high power cellular, packet data, and the wireline Public Switched Telecommunications Network (PSTN). Key goals included 1) designing data applications and an API suited to mobile users, 2) investigating internetworking issues, 3) characterizing wireless networks under various field conditions, and 4) comparing the performance of different protocol mechanisms over the diverse networks and applications. We describe experimental results for different protocol mechanisms and parameters, such as acknowledgment schemes and packet sizes. We show the need for powerful error control mechanisms such as selective acknowledgements and combining data from multiple transmissions. We highlight the possibility of a common protocol for all wireless networks, from micro-cellular PCS to satellite networks.

The natural history of conducting and reporting clinical trials: interviews with trialists.

PubMed

Smyth, Rebecca M D; Jacoby, Ann; Altman, Douglas G; Gamble, Carrol; Williamson, Paula R

2015-01-26

To investigate the nature of the research process as a whole, factors that might influence the way in which research is carried out, and how researchers ultimately report their findings. Semi-structured qualitative telephone interviews with authors of trials, identified from two sources: trials published since 2002 included in Cochrane systematic reviews selected for the ORBIT project; and trial reports randomly sampled from 14,758 indexed on PubMed over the 12-month period from August 2007 to July 2008. A total of 268 trials were identified for inclusion, 183 published since 2002 and included in the Cochrane systematic reviews selected for the ORBIT project and 85 randomly selected published trials indexed on PubMed. The response rate from researchers in the former group was 21% (38/183) and in the latter group was 25% (21/85). Overall, 59 trialists were interviewed from the two different sources. A number of major but related themes emerged regarding the conduct and reporting of trials: establishment of the research question; identification of outcome variables; use of and adherence to the study protocol; conduct of the research; reporting and publishing of findings. Our results reveal that, although a substantial proportion of trialists identify outcome variables based on their clinical experience and knowing experts in the field, there can be insufficient reference to previous research in the planning of a new trial. We have revealed problems with trial recruitment: not reaching the target sample size, over-estimation of recruitment potential and recruiting clinicians not being in equipoise. We found a wide variation in the completeness of protocols, in terms of detailing study rationale, outlining the proposed methods, trial organisation and ethical considerations. Our results confirm that the conduct and reporting of some trials can be inadequate. Interviews with researchers identified aspects of clinical research that can be especially challenging: establishing appropriate and relevant outcome variables to measure, use of and adherence to the study protocol, recruiting of study participants and reporting and publishing the study findings. Our trialists considered the prestige and impact factors of academic journals to be the most important criteria for selecting those to which they would submit manuscripts.

Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya Aids Vaccine Initiative (KAVI), Kenya

PubMed Central

Omosa-Manyonyi, Gloria S.; Jaoko, Walter; Anzala, Omu; Ogutu, Hilda; Wakasiaka, Sabina; Malogo, Roselyn; Nyange, Jacqueline; Njuguna, Pamela; Ndinya-Achola, Jeckoniah; Bhatt, Kirana; Farah, Bashir; Oyaro, Micah; Schmidt, Claudia; Priddy, Frances; Fast, Patricia

2011-01-01

Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted. PMID:21283743

A cluster randomised feasibility trial evaluating six-month nutritional interventions in the treatment of malnutrition in care home-dwelling adults: recruitment, data collection and protocol.

PubMed

Stow, Ruth; Rushton, Alison; Ives, Natalie; Smith, Christina; Rick, Caroline

2015-01-01

Protein energy malnutrition predisposes individuals to disease, delays recovery from illness and reduces quality of life. Care home residents are especially vulnerable, with an estimated 30%-42% at risk. There is no internationally agreed protocol for the nutritional treatment of malnutrition in the care home setting. Widely used techniques include food-based intervention and/or the use of prescribed oral nutritional supplements, but a trial comparing the efficacy of interventions is necessary. In order to define outcomes and optimise the design for an adequately powered, low risk of bias cluster randomised controlled trial, a feasibility trial with 6-month intervention is being run, to assess protocol procedures, recruitment and retention rates, consent processes and resident and staff acceptability. Trial recruitment began in September 2013 and concluded in December 2013. Six privately run care homes in Solihull, England, were selected to establish feasibility within different care home types. Residents with or at risk of malnutrition with no existing dietetic intervention in place were considered for receipt of the allocated intervention. Randomisation took place at the care home level, using a computer-generated random number list to allocate each home to either a dietetic intervention arm (food-based or prescribed supplements) or the standard care arm, continued for 6 months. Dietetic intervention aimed to increase daily calorie intake by 600 kcal and protein by 20-25 g. The primary outcomes will be trial feasibility and acceptability of trial design and allocated interventions. A range of outcome assessments and data collection tools will be evaluated for feasibility, including change in nutrient intake, anthropometric parameters and patient-centric measures, such as quality of life and self-perceived appetite. The complexities inherent in care home research has resulted in the under representation of this population in research trials. The results of this feasibility trial will be used to inform the development and design of a future cluster randomised controlled trial to compare food-based intervention with prescribed oral nutritional supplements (ONS) in the treatment of malnutrition within the care home population. Current Controlled Trials ISRCTN38047922.

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

2015-01-01

Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

The second Randomised Evaluation of the Effectiveness, cost-effectiveness and Acceptability of Computerised Therapy (REEACT-2) trial: does the provision of telephone support enhance the effectiveness of computer-delivered cognitive behaviour therapy? A randomised controlled trial.

PubMed

Brabyn, Sally; Araya, Ricardo; Barkham, Michael; Bower, Peter; Cooper, Cindy; Duarte, Ana; Kessler, David; Knowles, Sarah; Lovell, Karina; Littlewood, Elizabeth; Mattock, Richard; Palmer, Stephen; Pervin, Jodi; Richards, David; Tallon, Debbie; White, David; Walker, Simon; Worthy, Gillian; Gilbody, Simon

2016-11-01

Computerised cognitive behaviour therapy (cCBT) is an efficient form of therapy potentially improving access to psychological care. Indirect evidence suggests that the uptake and effectiveness of cCBT can be increased if facilitated by telephone, but this is not routinely offered in the NHS. To compare the clinical effectiveness and cost-effectiveness of telephone-facilitated free-to-use cCBT [e.g. MoodGYM (National Institute for Mental Health Research, Australian National University, Canberra, ACT, Australia)] with minimally supported cCBT. This study was a multisite, pragmatic, open, two-arm, parallel-group randomised controlled trial with a concurrent economic evaluation. Participants were recruited from GP practices in Bristol, Manchester, Sheffield, Hull and the north-east of England. Potential participants were eligible to participate in the trial if they were adults with depression scoring ≥ 10 on the Patient Health Questionnaire-9 (PHQ-9). Participants were randomised using a computer-generated random number sequence to receive minimally supported cCBT or telephone-facilitated cCBT. Participants continued with usual general practitioner care. The primary outcome was self-reported symptoms of depression, as assessed by the PHQ-9 at 4 months post randomisation. Secondary outcomes were depression at 12 months and anxiety, somatoform complaints, health utility (as assessed by the European Quality of Life-5 Dimensions questionnaire) and resource use at 4 and 12 months. Clinical effectiveness: 182 participants were randomised to minimally supported cCBT and 187 participants to telephone-facilitated cCBT. There was a difference in the severity of depression at 4 and 12 months, with lower levels in the telephone-facilitated group. The odds of no longer being depressed (defined as a PHQ-9 score of < 10) at 4 months were twice as high in the telephone-facilitated cCBT group [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.23 to 3.42]. The benefit of telephone-facilitated cCBT was no longer significant at 12 months (OR 1.63, 95% CI 0.98 to 2.71). At 4 months the between-group difference in PHQ-9 scores was 1.9 (95% CI 0.5 to 3.3). At 12 months the results still favoured telephone-facilitated cCBT but were no longer statistically significant, with a difference in PHQ-9 score of 0.9 (95% CI -0.5 to 2.3). When considering the whole follow-up period, telephone-facilitated cCBT was asssociated with significantly lower PHQ-9 scores than minimally supported cCBT (mean difference -1.41, 95% CI -2.63 to -0.17; p  = 0.025). There was a significant improvement in anxiety scores over the trial period (between-group difference 1.1, 95% CI 0.1 to 2.3; p  = 0.037). In the case of somatic complaints (assessed using the Patient Health Questionnaire-15), there was a borderline statistically significant difference over the trial period (between-group difference 1.1, 95% CI 0.0 to 1.8; p  = 0.051). There were gains in quality-adjusted life-years at reduced cost when telephone facilitation was added to MoodGYM. However, the results were subject to uncertainty. The results showed short-term benefits from the addition of telephone facilitation to cCBT. The effect was small to moderate and comparable with that of other primary care psychological interventions. Telephone facilitation should be considered when offering cCBT for depression. Participants' depression was assessed with the PHQ-9, cCBT use was quite low and there was a slightly greater than anticipated loss to follow-up. Improve the acceptability of cCBT and its capacity to address coexisting disorders. Large-scale pragmatic trials of cCBT with bibliotherapy and telephone-based interventions are required. Current Controlled Trials ISRCTN55310481. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 89. See the NIHR Journals Library website for further project information.

Description of the Protocols for Randomized Controlled Trials on Cancer Drugs Conducted in Spain (1999–2003)

PubMed Central

Bonfill, Xavier; Ballesteros, Mónica; Gich, Ignasi; Serrano, María Antonia; García López, Fernando; Urrútia, Gerard

2013-01-01

Objective To describe the characteristics of randomized controlled clinical trials (RCT) on cancer drugs conducted in Spain between 1999 and 2003 based on their protocols. Methods We conducted an observational retrospective cohort study to identify the protocols of RCTs on cancer drugs authorized by the Agencia Española del Medicamento y Productos Sanitarios (AEMPS) (Spanish Agency for Medicines and Medical Devices) during 1999-2003. A descriptive analysis was completed and the association between variables based on the study setting and sponsorship were assessed. Results We identified a total of 303 protocols, which included 176,835 potentially eligible patients. Three-quarter of the studies were internationally-based, 61.7% were phase III, and 76.2% were sponsored by pharmaceutical companies. The most frequently assessed outcomes were response rate (24.7%), overall survival (20.7%), and progression-free survival (14.5%). Of all protocols, 10.6% intended to include more than 1000 patients (mean: 2442, SD: 2724). Compared with their national counterparts, internationally-based studies were significantly larger (p<0.001) and were more likely to implement centralized randomization (p<0.001), blinding of the intervention (p<0.001), and survival as primary outcome (p<0.001). Additionally, most internationally-based studies were sponsored by pharmaceutical companies (p<0.01). In a high percentage of protocols, the available information was not explicit enough to assess the validity of each trial. Compared to other European countries, the proportion of Spanish cancer drugs protocols registered at www.clinicaltrials.gov (7%) was lower. Conclusion RCTs on cancer drugs conducted in Spain between 1999 and 2003 were more likely to be promoted by pharmaceutical companies rather than by non-profit national groups. The former were more often part of international studies, which generally had better methodological quality than national ones. There are some worldwide on-going initiatives that aim to increase the transparency and quality of future research. PMID:24236154

Pediatric Diabetic Ketoacidosis, Fluid Therapy and Cerebral Injury: The Design of a Factorial Randomized Controlled Trial

PubMed Central

Glaser, Nicole S.; Ghetti, Simona; Casper, T. Charles; Dean, J. Michael; Kuppermann, Nathan

2013-01-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the United States and worldwide. The optimal protocol for intravenous fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of intravenous fluid infusion and the development of cerebral edema, the most common and most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and cerebral edema have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (Fluid Therapies Under Investigation in DKA) Study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial-design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically-overt CE, and long-term neurocognitive outcomes following DKA. PMID:23490311

Effects of Vestibular Rehabilitation on Balance Control in Older People with Chronic Dizziness: A Randomized Clinical Trial.

PubMed

Ricci, Natalia Aquaroni; Aratani, Mayra Cristina; Caovilla, Heloísa Helena; Ganança, Fernando Freitas

2016-04-01

The aim of this study was to compare the effects of vestibular rehabilitation protocols on balance control in elderly with dizziness. This is a randomized clinical trial with 3-mo follow-up period. The sample was composed of 82 older individuals with chronic dizziness from vestibular disorders. The control group was treated according to the Conventional Cawthorne & Cooksey protocol (n = 40), and the experimental group was submitted to a Multimodal Cawthorne & Cooksey protocol (n = 42). Measures included Dynamic Gait Index, fall history, hand grip strength, Time Up-and-Go Test, sit-to-stand test, multidirectional reach, and static balance tests. With the exception of history of falls, Forward Functional Reach, Unipedal Right and Left Leg Eyes Closed, and Sensorial Romberg Eyes Open, all outcomes improved after treatments. Such results persisted at follow-up period, with the exception of the Tandem Eyes Open and the Timed Up-and-Go manual. The between-group differences for Sensorial Romberg Eyes Closed (4.27 secs) and Unipedal Left Leg Eyes Open (4.08 secs) were significant after treatment, favoring the Multimodal protocol. Both protocols resulted in improvement on elderly's balance control, which was maintained during a short-term period. The multimodal protocol presented better performance on specific static balance tests.

Effectiveness of a transdiagnostic internet-based protocol for the treatment of emotional disorders versus treatment as usual in specialized care: study protocol for a randomized controlled trial.

PubMed

González-Robles, Alberto; García-Palacios, Azucena; Baños, Rosa; Riera, Antonio; Llorca, Ginés; Traver, Francisco; Haro, Gonzalo; Palop, Vicente; Lera, Guillem; Romeu, José Enrique; Botella, Cristina

2015-10-31

Emotional disorders (depression and anxiety disorders) are highly prevalent mental health problems. Although evidence showing the effectiveness of disorder-specific treatments exists, high comorbidity rates among emotional disorders limit the utility of these protocols. This has led some researchers to focus their interest on transdiagnostic interventions, a treatment perspective that might be more widely effective across these disorders. Also, the current way of delivering treatments makes it difficult provide assistance to all of the population in need. The use of the Internet in the delivery of evidence-based treatments may help to disseminate treatments among the population. In this study, we aim to test the effectiveness of EmotionRegulation, a new transdiagnostic Internet-based protocol for unipolar mood disorders, five anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder and anxiety disorder not otherwise specified), and obsessive-compulsive disorder in comparison to treatment as usual as provided in Spanish public specialized mental health care. We will also study its potential impact on basic temperament dimensions (neuroticism/behavioral inhibition and extraversion/behavioral activation). Expectations and opinions of patients about this protocol will also be studied. The study is a randomized controlled trial. 200 participants recruited in specialized care will be allocated to one of two treatment conditions: a) EmotionRegulation or b) treatment as usual. Primary outcome measures will be the BAI and the BDI-II. Secondary outcomes will include a specific measure of the principal disorder, and measures of neuroticism/behavioral inhibition and extraversion/behavioral activation. Patients will be assessed at baseline, post-treatment, and 3- and 12-month follow-ups. Intention to treat and per protocol analyses will be performed. Although the effectiveness of face-to-face transdiagnostic protocols has been investigated in previous studies, the number of published transdiagnostic Internet-based programs is still quite low. To our knowledge, this is the first randomized controlled trial studying the effectiveness of a transdiagnostic Internet-based treatment for several emotional disorders in public specialized care. Combining both a transdiagnostic approach with an Internet-based therapy format may help to decrease the burden of mental disorders, reducing the difficulties associated with disorder-specific treatments and facilitating access to people in need of treatment. Strengths and limitations are discussed. ClinicalTrials.gov NCT02345668 . Registered 27 July 2015.

Performance of Stochastic Targeted Blood Glucose Control Protocol by virtual trials in the Malaysian intensive care unit.

PubMed

Jamaludin, Ummu K; M Suhaimi, Fatanah; Abdul Razak, Normy Norfiza; Md Ralib, Azrina; Mat Nor, Mohd Basri; Pretty, Christopher G; Humaidi, Luqman

2018-08-01

Blood glucose variability is common in healthcare and it is not related or influenced by diabetes mellitus. To minimise the risk of high blood glucose in critically ill patients, Stochastic Targeted Blood Glucose Control Protocol is used in intensive care unit at hospitals worldwide. Thus, this study focuses on the performance of stochastic modelling protocol in comparison to the current blood glucose management protocols in the Malaysian intensive care unit. Also, this study is to assess the effectiveness of Stochastic Targeted Blood Glucose Control Protocol when it is applied to a cohort of diabetic patients. Retrospective data from 210 patients were obtained from a general hospital in Malaysia from May 2014 until June 2015, where 123 patients were having comorbid diabetes mellitus. The comparison of blood glucose control protocol performance between both protocol simulations was conducted through blood glucose fitted with physiological modelling on top of virtual trial simulations, mean calculation of simulation error and several graphical comparisons using stochastic modelling. Stochastic Targeted Blood Glucose Control Protocol reduces hyperglycaemia by 16% in diabetic and 9% in nondiabetic cohorts. The protocol helps to control blood glucose level in the targeted range of 4.0-10.0 mmol/L for 71.8% in diabetic and 82.7% in nondiabetic cohorts, besides minimising the treatment hour up to 71 h for 123 diabetic patients and 39 h for 87 nondiabetic patients. It is concluded that Stochastic Targeted Blood Glucose Control Protocol is good in reducing hyperglycaemia as compared to the current blood glucose management protocol in the Malaysian intensive care unit. Hence, the current Malaysian intensive care unit protocols need to be modified to enhance their performance, especially in the integration of insulin and nutrition intervention in decreasing the hyperglycaemia incidences. Improvement in Stochastic Targeted Blood Glucose Control Protocol in terms of u en model is also a must to adapt with the diabetic cohort. Copyright © 2018 Elsevier B.V. All rights reserved.

Patient-Centred Innovations for Persons with Multimorbidity: funded evaluation protocol.

PubMed

Stewart, Moira; Fortin, Martin

2017-05-09

The high prevalence of multimorbidity necessitates rethinking of the health care system. The overarching goal of the Patient-Centred Innovations for Persons with Multimorbidity program is to build on existing structures and find and evaluate patient-centred innovations relevant to multimorbidity. We describe the protocol for a proposed multijurisdictional (Quebec and Ontario) concurrent triangulation mixed-methods study. In both provinces, a qualitative descriptive study will be used to explore innovations in patient-centred multimorbidity care. Two randomized controlled trials, 1 in either province, will evaluate the innovations in a wait-list-controlled design using patient-reported outcomes. An additional control group, matched on age, sex, enrolment/index date (± 3 mo) and propensity score, will be created with the use of health administrative data. Patients will be 18-80 years of age and will have 3 or more chronic conditions. The innovations will have elements of relevance to multimorbidity care, patient-centred partnerships and integration of care. The primary outcome measures will be 2 patient-reported outcomes: patient education and self-efficacy. Secondary outcomes will include patient-reported health status, quality of life, psychological distress and health behaviours, and costs of care. This protocol describes a mixed-method study in 2 jurisdictions. The studies will answer the questions of what innovations work and how they work for patients, health care professionals and policy-makers. Trial registration: ClinicalTrials.gov, no NCT02789800 (Quebec Trial), NCT02742597 (Ontario Trial). Copyright 2017, Joule Inc. or its licensors.

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; Lin, Zhengkun; Wang, Qin; Liu, Feiwen; Liu, Jiao; Fang, Yunhua; Chen, Shanjia; Zhou, Xiaoxuan; Hong, Wenjun; Wu, Jinsong; Madrigal-Mora, Natalia; Zheng, Guohua; Yang, Shanli; Tao, Jing; Chen, Lidian

2015-06-16

Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Overcoming recruitment challenges in palliative care clinical trials.

PubMed

LeBlanc, Thomas W; Lodato, Jordan E; Currow, David C; Abernethy, Amy P

2013-11-01

Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.

Ensuring Quality in AFRINEST and SATT

PubMed Central

2013-01-01

Background: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials. Methods: A critical component of quality control for AFRINEST and SATT was striving to eliminate variation in clinical assessments and decisions regarding eligibility, enrollment and treatment outcomes. Ensuring appropriate and consistent clinical judgment was accomplished through standardized approaches applied across the trials, including training, assessment of clinical skills and refresher training. Standardized monitoring procedures were also applied across the trials, including routine (day-to-day) internal monitoring of performance and adherence to protocols, systematic external monitoring by funding agencies and external monitoring by experienced, independent trial monitors. A group of independent experts (Technical Steering Committee/Technical Advisory Group) provided regular monitoring and technical oversight for the trials. Conclusions: Harmonization of AFRINEST and SATT have helped to ensure consistency and quality of implementation, both internally and across the trials as a whole, thereby minimizing potential threats to the validity of the trials’ results. PMID:23945575

Effectiveness of Aquatic Therapy vs Land-based Therapy for Balance and Pain in Women with Fibromyalgia: a study protocol for a randomised controlled trial.

PubMed

Rivas Neira, Sabela; Pasqual Marques, Amélia; Pegito Pérez, Irene; Fernández Cervantes, Ramón; Vivas Costa, Jamile

2017-01-19

Fibromyalgia is a disease with an increasing incidence. It impairs the quality of life of patients and decreases their functional capacity. Aquatic therapy has already been used for managing the symptoms of this syndrome. However, aquatic therapy has only recently been introduced as a treatment modality for improving proprioception in fibromyalgia. The main objective of this study is to determine the effectiveness of two physiotherapy protocols, one in and one out of water, for improving balance and decreasing pain in women with fibromyalgia. The study protocol will be a single-blind randomised controlled trial. Forty women diagnosed with fibromyalgia will be randomly assigned into 2 groups: Aquatic Therapy (n = 20) or Land-based Therapy (n = 20). Both interventions include 60-min therapy sessions, structured into 4 sections: Warm-up, Proprioceptive Exercises, Stretching and Relaxation. These sessions will be carried out 3 times a week for 3 months. Primary outcomes are balance (static and dynamic) and pain (intensity and threshold). Secondary outcomes include functional balance, quality of life, quality of sleep, fatigue, self-confidence in balance and physical ability. Outcome measures will be evaluated at baseline, at the end of the 3-month intervention period, and 6-weeks post-treatment. Statistical analysis will be carried out using the SPSS 21.0 program for Windows and a significance level of p ≤ 0.05 will be used for all tests. This study protocol details two physiotherapy interventions in women with fibromyalgia to improve balance and decrease pain: aquatic therapy and land-based therapy. In current literature there is a lack of methodological rigour and a limited number of studies that describe physiotherapy protocols to manage fibromyalgia symptoms. High-quality scientific works are required to highlight physiotherapy as one of the most recommended treatment options for this syndrome. Date of publication in ClinicalTrials.gov: 18/02/2016. ClinicalTrials.gov Identifier: NCT02695875 .

Validation of the phase II feasibility study in a palliative care setting: gastrografin in malignant bowel obstruction.

PubMed

Lee, Cindy; Vather, Ryash; O'Callaghan, Anne; Robinson, Jackie; McLeod, Briar; Findlay, Michael; Bissett, Ian

2013-12-01

Malignant bowel obstruction (MBO) is common in patients with advanced cancer. To perform a phase II study to assess the feasibility of conducting a phase III trial investigating the therapeutic value of gastrografin in MBO. Randomized double-blinded placebo-controlled feasibility study. Participants received 100 mL of either gastrografin or placebo. Over 8 months, 57 patients were screened and 9 enrolled (15.8% recruitment rate). Of the 9 enrolled, 4 received gastrografin (with 2 completing assessment) and 5 received placebo (with 4 completing assessment). It is not feasible to conduct a phase III trial using the same study protocol. This study validates the use of the phase II feasibility study to assess protocol viability in a palliative population prior to embarking on a larger trial.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: protocol for a feasibility randomized pilot trial.

PubMed

Johnstone, Jennie; Meade, Maureen; Marshall, John; Heyland, Daren K; Surette, Michael G; Bowdish, Dawn Me; Lauzier, Francois; Thebane, Lehana; Cook, Deborah J

2015-01-01

Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate. Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 10 10 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded. The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and hospital length of stay, and mortality. The morbidity, mortality, and cost of VAP underscore the need for cost-effective prophylactic interventions. The PROSPECT Pilot Trial is the initial step toward rigorously evaluating whether probiotics decrease nosocomial infections, have no effect, or actually cause infections in critically ill patients. ClinicalTrials.gov. NCT01782755.

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial

PubMed Central

2010-01-01

Background This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Methods and Design Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms. Discussion This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings. Trial registration ISRCTN24952438 PMID:20964860

Evaluation of a novel device for the management of high blood pressure and shock in pregnancy in low-resource settings: study protocol for a stepped-wedge cluster-randomised controlled trial (CRADLE-3 trial).

PubMed

Nathan, Hannah L; Duhig, Kate; Vousden, Nicola; Lawley, Elodie; Seed, Paul T; Sandall, Jane; Bellad, Mrutyunjaya B; Brown, Adrian C; Chappell, Lucy C; Goudar, Shivaprasad S; Gidiri, Muchabayiwa F; Shennan, Andrew H

2018-03-27

Obstetric haemorrhage, sepsis and pregnancy hypertension account for more than 50% of maternal deaths worldwide. Early detection and effective management of these conditions relies on vital signs. The Microlife® CRADLE Vital Sign Alert (VSA) is an easy-to-use, accurate device that measures blood pressure and pulse. It incorporates a traffic-light early warning system that alerts all levels of healthcare provider to the need for escalation of care in women with obstetric haemorrhage, sepsis or pregnancy hypertension, thereby aiding early recognition of haemodynamic instability and preventing maternal mortality and morbidity. The aim of the trial was to determine whether implementation of the CRADLE intervention (the Microlife® CRADLE VSA device and CRADLE training package) into routine maternity care in place of existing equipment will reduce a composite outcome of maternal mortality and morbidity in low- and middle-income country populations. The CRADLE-3 trial was a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care. Each cluster crossed from routine maternity care to the intervention at 2-monthly intervals over the course of 20 months (April 2016 to November 2017). All women identified as pregnant or within 6 weeks postpartum, presenting for maternity care in cluster catchment areas were eligible to participate. Primary outcome data (composite of maternal death, eclampsia and emergency hysterectomy per 10,000 deliveries) were collected at 10 clusters (Gokak, Belgaum, India; Harare, Zimbabwe; Ndola, Zambia; Lusaka, Zambia; Free Town, Sierra Leone; Mbale, Uganda; Kampala, Uganda; Cap Haitien, Haiti; South West, Malawi; Addis Ababa, Ethiopia). This trial was informed by the Medical Research Council guidance for complex interventions. A process evaluation was undertaken to evaluate implementation in each site and a cost-effectiveness evaluation will be undertaken. All aspects of this protocol have been evaluated in a feasibility study, with subsequent optimisation of the intervention. This trial will demonstrate the potential impact of the CRADLE intervention on reducing maternal mortality and morbidity in low-resource settings. It is anticipated that the relatively low cost of the intervention and ease of integration into existing health systems will be of significant interest to local, national and international health policy-makers. ISCRTN41244132. Registered on 2 February 2016. Prospective protocol modifications have been recorded and were communicated to the Ethics Committees and Trials Committees. The adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist and the SPIRIT Checklist are attached as Additional file 1.

Tolerance - One Transplant for Life

PubMed Central

Kawai, Tatsuo; Leventhal, Joseph; Madsen, Joren C.; Strober, Samuel; Turka, Laurence A.; Wood, Kathryn J.

2014-01-01

A recent TTS workshop was convened to address the question: “What do we need to have in place to make tolerance induction protocols a “standard of care” for organ transplant recipients over the next decade?” In a productive two day meeting there was wide-ranging discussion on a broad series of topics resulting in five consensus recommendations: (1) Establish a registry of results for patients enrolled in tolerance trials; (2) Establish standardized protocols for sample collection and storage; (3) Establish standardized biomarkers and assays; (4) Include children aged 12 and older in protocols that have been validated in adults; (5) a task force to engage third party payers in discussions of how to fund tolerance trials. Future planned workshops will focus on progress in implementing these recommendations and identifying other steps that the community needs to take. PMID:24926829

Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de). PMID:24884848

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial.

PubMed

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-08-20

Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. ISRCTN03978701. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Differences in Reporting of Analyses in Internal Company Documents Versus Published Trial Reports: Comparisons in Industry-Sponsored Trials in Off-Label Uses of Gabapentin

PubMed Central

Vedula, S. Swaroop; Li, Tianjing; Dickersin, Kay

2013-01-01

Background Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. Methods and Findings For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses). Conclusions Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded. Please see later in the article for the Editors' Summary PMID:23382656

Initiating change locally in bullying and aggression through the school environment (INCLUSIVE) trial: update to cluster randomised controlled trial protocol.

PubMed

Bonell, Chris; Mathiot, Anne; Allen, Elizabeth; Bevilacqua, Leonardo; Christie, Deborah; Elbourne, Diana; Fletcher, Adam; Grieve, Richard; Legood, Rosa; Scott, Stephen; Warren, Emily; Wiggins, Meg; Viner, Russell M

2017-05-25

Systematic reviews suggest that multi-component interventions are effective in reducing bullying victimisation and perpetration. We are undertaking a phase III randomised trial of the INCLUSIVE multi-component intervention. This trial aims to assess the effectiveness and cost-effectiveness of the INCLUSIVE intervention in reducing aggression and bullying victimisation in English secondary schools. This paper updates the original trial protocol published in 2014 (Trials 15:381, 2014) and presents the changes in the process evaluation protocol and the secondary outcome data collection. The methods are summarised as follows. cluster randomised trial. 40 state secondary schools. Outcomes assessed among the cohort of students at the end of year 7 (n = 6667) at baseline. INCLUSIVE is a multi-component school intervention including a social and emotional learning curriculum, changes to school environment (an action group comprising staff and students reviews local data on needs to review rules and policies and determine other local actions) and staff training in restorative practice. The intervention will be delivered by schools supported in the first two years by educational facilitators independent of the research team, with a third intervention year involving no external facilitation but all other elements. Comparator: normal practice. Primary: Two primary outcomes at student level assessed at baseline and at 36 months: 1. Aggressive behaviours in school: Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale (ESYTC) 2. Bullying and victimisation: Gatehouse Bullying Scale (GBS) Secondary outcomes assessed at baseline, 24 and 36 months will include measures relating to the economic evaluation, psychosocial outcomes in students and staff and school-level truancy and exclusion rates. 20 schools per arm will provide 90% power to identify an effect size of 0.25 SD with a 5% significance level. Randomisation: eligible consenting schools were randomised stratified for single-sex versus mixed-sex schools, school-level deprivation and measures of school attainment. The trial involves independent research and intervention teams and is supervised by a Trial Steering Committee and a Data Monitoring Committee. Current Controlled Trials, ISRCTN10751359 . Registered on 11 March 2014.

'Be active, eat right', evaluation of an overweight prevention protocol among 5-year-old children: design of a cluster randomised controlled trial.

PubMed

Veldhuis, Lydian; Struijk, Mirjam K; Kroeze, Willemieke; Oenema, Anke; Renders, Carry M; Bulk-Bunschoten, Anneke Mw; Hirasing, Remy A; Raat, Hein

2009-06-08

The prevalence of overweight and obesity in children has at least doubled in the past 25 years with a major impact on health. In 2005 a prevention protocol was developed applicable within Youth Health Care. This study aims to assess the effects of this protocol on prevalence of overweight and health behaviour among children. A cluster randomised controlled trial is conducted among 5-year-old children included by 44 Youth Health Care teams randomised within 9 Municipal Health Services. The teams are randomly allocated to the intervention or control group. The teams measure the weight and height of all children. When a child in the intervention group is detected with overweight according to the international age and gender specific cut-off points of BMI, the prevention protocol is applied. According to this protocol parents of overweight children are invited for up to three counselling sessions during which they receive personal advice about a healthy lifestyle, and are motivated for and assisted in behavioural change.The primary outcome measures are Body Mass Index and waist circumference of the children. Parents will complete questionnaires to assess secondary outcome measures: levels of overweight inducing/reducing behaviours (i.e. being physically active, having breakfast, drinking sweet beverages and watching television/playing computer games), parenting styles, parenting practices, and attitudes of parents regarding these behaviours, health-related quality of life of the children, and possible negative side effects of the prevention protocol. Data will be collected at baseline (when the children are aged 5 years), and after 12 and 24 months of follow-up. Additionally, a process and a cost-effectiveness evaluation will be conducted. In this study called 'Be active, eat right' we evaluate an overweight prevention protocol for use in the setting of Youth Health Care. It is hypothesized that the use of this protocol will result in a healthier lifestyle of the children and an improved BMI and waist circumference. Current Controlled Trials ISRCTN04965410.

Who's really hypertensive?--Quality control issues in the assessment of blood pressure for randomized trials.

PubMed

Reid, Christopher M; Ryan, Philip; Miles, Helen; Willson, Kristyn; Beilin, Laurence J; Brown, Mark A; Jennings, Garry L; Johnston, Colin I; Macdonald, Graham J; Marley, John E; McNeil, John J; Morgan, Trefor O; West, Malcolm J; Wing, Lindon M H

2005-01-01

The characterization of blood pressure in treatment trials assessing the benefits of blood pressure lowering regimens is a critical factor for the appropriate interpretation of study results. With numerous operators involved in the measurement of blood pressure in many thousands of patients being screened for entry into clinical trials, it is essential that operators follow pre-defined measurement protocols involving multiple measurements and standardized techniques. Blood pressure measurement protocols have been developed by international societies and emphasize the importance of appropriate choice of cuff size, identification of Korotkoff sounds, and digit preference. Training of operators and auditing of blood pressure measurement may assist in reducing the operator-related errors in measurement. This paper describes the quality control activities adopted for the screening stage of the 2nd Australian National Blood Pressure Study (ANBP2). ANBP2 is cardiovascular outcome trial of the treatment of hypertension in the elderly that was conducted entirely in general practices in Australia. A total of 54 288 subjects were screened; 3688 previously untreated subjects were identified as having blood pressure >140/90 mmHg at the initial screening visit, 898 (24%) were not eligible for study entry after two further visits due to the elevated reading not being sustained. For both systolic and diastolic blood pressure recording, observed digit preference fell within 7 percentage points of the expected frequency. Protocol adherence, in terms of the required minimum blood pressure difference between the last two successive recordings, was 99.8%. These data suggest that adherence to blood pressure recording protocols and elimination of digit preferences can be achieved through appropriate training programs and quality control activities in large multi-centre community-based trials in general practice. Repeated blood pressure measurement prior to initial diagnosis and study entry is essential to appropriately characterize hypertension in these elderly patients.

Pathological investigation of caries and occlusal pulpar exposure in donkey cheek teeth using computerised axial tomography with histological and ultrastructural examinations.

PubMed

Toit, Nicole du; Burden, Faith A; Kempson, Sue A; Dixon, Padraic M

2008-12-01

Post-mortem examination of 16 donkey cheek teeth (CT) with caries (both peripheral and infundibular) and pulpar exposure were performed using computerised axial tomography (CAT), histology and scanning electron microscopy. CAT imaging was found to be useful to assess the presence and extent of caries and pulp exposure in individual donkey CT. Histology identified the loss of occlusal secondary dentine, and showed pulp necrosis in teeth with pulpar exposure. Viable pulp was present more apically in one exposed pulp horn, with its occlusal aspect sealed off from the exposed aspect of the pulp horn by a false pulp stone. Scanning electron microscopy showed the amelo-cemental junction to be a possible route of bacterial infection in infundibular cemental caries. The basic pathogenesis of dental caries in donkeys appears very similar to its description in other species.

[Evaluation of residual osteomuscular function using computerised movement analysis for building sector workers: specificity and technical problem].

PubMed

D'Orso, M I; Centemeri, R; Latocca, R; Riva, M; Cesana, G

2012-01-01

Occupational Health Doctors active in building sector firms frequently have to evaluate residual workers' osteomuscular function in patients coming back to work after an accident happened during work time or free time. Definition of their specific individual work suitability is usually carried out utilizing semeiotic tests in which subjective evaluation of every single Medical Doctor is real important in definition of final results and this fact can cause legal controversies. In our research we describe the application of computerised movement analysis on 10 workers of building sector. In every patient examined this technical method has been able to study objectively the tridimensional ranges of motion of most important osteomuscular districts. The possibility to have an objective evaluation of residual osteomuscular function has a relevant importance both in definition of workers' work suitability at the moment in which they start again their activities and in possible future legal conflicts.

Geospatial Data for Computerisation of Public Administration in the Czech Republic

NASA Astrophysics Data System (ADS)

Cada, V.; Mildorf, T.

2011-08-01

The main aim of the eGovernment programme in the Czech Republic is to enhance the efficiency of public administration. The Digital Map of Public Administration (DMVS) should be composed of digital orthophotographs of the Czech Republic, digital and digitised cadastral maps, digital purpose cadastral map (ÚKM) and a technical map of municipality, if available. The DMVS project is a part of computerisation of public administration in the Czech Republic. The project enhances the productivity of government administration and also simplifies the processes between citizens and public administration. The DMVS project, that should be compliant with the INSPIRE (Infrastructure for Spatial Information in the European Community) initiative, generates definite demand for geodata on the level of detail of land data model. The user needs that are clearly specified and required are not met due to inconsistencies in terminology, data management and level of detail.

[Computerised monitoring of integrated cervical screening. Indicators of diagnostic performance].

PubMed

Bucchi, L; Pierri, C; Amadori, A; Folicaldi, S; Ghidoni, D; Nannini, R; Bondi, A

2003-12-01

In a previous issue of this journal, we presented the background, rationale, general methods, and indicators of participation of a computerised system for the monitoring of integrated cervical screening, i.e. the integration of spontaneous Pap smear practice into organised screening. We also reported the results of the application of those indicators in the general database of the Pathology Department of Imola Health District in northern Italy. In the current paper, we present the rationale and definitions of indicators of diagnostic performance (total Pap smears and rate of unsatisfactory Pap smears, distribution by cytology class reported, rate of patients without timely follow-up, detection rate, positive predictive value, distribution of cytology classes reported by histology diagnosis, and distribution of cases of CIN and carcinoma registered by detection modality) as well as the results of their application in the same database as above.

Pathologists dislike sound? Evaluation of a computerised training microscope.

PubMed Central

Gray, E; Duvall, E; Sprey, J; Bird, C C

1998-01-01

AIM: To evaluate the use of multimedia enhancements, using a computerised microscope, in the training of microscope skills. METHODS: The HOME microscope provides facilities to highlight features of interest in conjunction with either text display or aural presentation. A pilot study was carried out with 10 individuals, eight of whom were at different stages of pathology training. A tutorial was implemented employing sound or text, and each individual tested each version. Both the subjective impressions of users and objective measurement of their patterns of use were recorded. RESULTS: Although both versions improved learning, users took longer to work through the aural than the text version; 90% of users preferred the text only version, including all eight individuals involved in pathology training. CONCLUSIONS: Pathologists appear to prefer visual rather than aural input when using teaching systems such as the HOME microscope and sound does not give added value to the training experience. Images PMID:9659250

The accuracy of real-time procedure coding by theatre nurses: a comparison with the central national system.

PubMed

Maclean, Donald; Younes, Hakim Ben; Forrest, Margaret; Towers, Hazel K

2012-03-01

Accurate and timely clinical data are required for clinical and organisational purposes and is especially important for patient management, audit of surgical performance and the electronic health record. The recent introduction of computerised theatre management systems has enabled real-time (point-of-care) operative procedure coding by clinical staff. However the accuracy of these data is unknown. The aim of this Scottish study was to compare the accuracy of theatre nurses' real-time coding on the local theatre management system with the central Scottish Morbidity Record (SMR01). Paired procedural codes were recorded, qualitatively graded for precision and compared (n = 1038). In this study, real-time, point-of-care coding by theatre nurses resulted in significant coding errors compared with the central SMR01 database. Improved collaboration between full-time coders and clinical staff using computerised decision support systems is suggested.

Computer-assisted image processing to detect spores from the fungus Pandora neoaphidis.

PubMed

Korsnes, Reinert; Westrum, Karin; Fløistad, Erling; Klingen, Ingeborg

2016-01-01

This contribution demonstrates an example of experimental automatic image analysis to detect spores prepared on microscope slides derived from trapping. The application is to monitor aerial spore counts of the entomopathogenic fungus Pandora neoaphidis which may serve as a biological control agent for aphids. Automatic detection of such spores can therefore play a role in plant protection. The present approach for such detection is a modification of traditional manual microscopy of prepared slides, where autonomous image recording precedes computerised image analysis. The purpose of the present image analysis is to support human visual inspection of imagery data - not to replace it. The workflow has three components:•Preparation of slides for microscopy.•Image recording.•Computerised image processing where the initial part is, as usual, segmentation depending on the actual data product. Then comes identification of blobs, calculation of principal axes of blobs, symmetry operations and projection on a three parameter egg shape space.

Prediction by computerised tomography of distance from skin to epidural space during thoracic epidural insertion.

PubMed

Carnie, J; Boden, J; Gao Smith, F

2002-07-01

In this single group observational study on 29 patients, we describe a technique that predicts the depth of the epidural space, calculated from the routine pre-operative chest computerised tomography (CT) scan using Pythagorean triangle trigonometry. We also compared the CT-derived depth of the epidural space with the actual depth of needle insertion. The CT-derived and the actual depths of the epidural space were highly correlated (r = 0.88, R2 = 0.78, p < 0.0001). The mean (95% CI) difference between CT-derived and actual depths was 0.26 (0.03-0.49) cm. Thus, the CT-derived depth tends to be greater than the actual depth by between 0.03 and 0.49 cm. There were no associations between either the CT-derived or the actual depth of the epidural space and age, weight, height or body mass index.

Combined Protocol for Acute Malnutrition Study (ComPAS) in rural South Sudan and urban Kenya: study protocol for a randomized controlled trial.

PubMed

Bailey, Jeanette; Lelijveld, Natasha; Marron, Bethany; Onyoo, Pamela; Ho, Lara S; Manary, Mark; Briend, André; Opondo, Charles; Kerac, Marko

2018-04-24

Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings. This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ≥125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted. If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme. ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.

Positive imagery cognitive bias modification (CBM) and internet-based cognitive behavioural therapy (iCBT) versus control CBM and iCBT for depression: study protocol for a parallel-group randomised controlled trial.

PubMed

Williams, Alishia D; Blackwell, Simon E; Holmes, Emily A; Andrews, Gavin

2013-10-29

The current randomised controlled trial will evaluate the efficacy of an internet-delivered positive imagery cognitive bias modification (CBM) intervention for depression when compared with an active control condition and help establish the additive benefit of positive imagery CBM when delivered in combination with internet cognitive behavioural therapy for depression. Patients meeting diagnostic criteria for a current major depressive episode will be recruited through the research arm of a not-for-profit clinical and research unit in Australia. The minimum sample size for each group (α set at 0.05, power at 0.80) was identified as 29, but at least 10% more will be recruited to hedge against expected attrition. We will measure the impact of CBM on primary measures of depressive symptoms (Beck Depression Inventory-second edition (BDI-II), Patient Health Questionnaire (PHQ9)) and interpretive bias (ambiguous scenarios test-depression), and on a secondary measure of psychological distress (Kessler-10 (K10)) following the 1-week CBM intervention. Secondary outcome measures of psychological distress (K10), as well as disability (WHO disability assessment schedule-II), repetitive negative thinking (repetitive thinking questionnaire), and anxiety (state trait anxiety inventory-trait version) will be evaluated following completion of the 11-week combined intervention, in addition to the BDI-II and PHQ9. Intent-to-treat marginal and mixed effect models using restricted maximum likelihood estimation will be used to evaluate the primary hypotheses. Clinically significant change will be defined as high-end state functioning (a BDI-II score <14) combined with a total score reduction greater than the reliable change index score. Maintenance of gains will be assessed at 3-month follow-up. The current trial protocol has been approved by the Human Research Ethics Committee of St Vincent's Hospital and the University of New South Wales, Sydney. Australian New Zealand Clinical Trials Registry: ACTRN12613000139774 and Clinicaltrials.gov: NCT01787513. This trial protocol is written in compliance with the Standard Protocol Items: recommendations for Interventional Trials (SPIRIT) guidelines.

Initial non-operative management of uncomplicated appendicitis in children: a protocol for a multicentre randomised controlled trial (APAC trial)

PubMed Central

Knaapen, Max; van der Lee, Johanna H; Bakx, Roel; The, Sarah-May L; van Heurn, Ernst W E; Heij, Hugo A; Gorter, Ramon R

2017-01-01

Introduction Based on epidemiological, immunological and pathology data, the idea that appendicitis is not necessarily a progressive disease is gaining ground. Two types are distinguished: simple and complicated appendicitis. Non-operative treatment (NOT) of children with simple appendicitis has been investigated in several small studies. So far, it is deemed safe. However, its effectiveness and effect on quality of life (QoL) have yet to be established in an adequately powered randomised trial. In this article, we provide the study protocol for the APAC (Antibiotics versus Primary Appendectomy in Children) trial. Methods and analysis This multicentre, non-inferiority, randomised controlled trial randomises children aged 7–17 years with imaging-confirmed simple appendicitis between appendectomy and NOT. Patients are recruited in 15 hospitals. The intended sample size, based on the primary outcome, rate of complications and a non-inferiority margin of 5%, is 334 patients. NOT consists of intravenous antibiotics for 48–72 hours, daily blood tests and ultrasound follow-up. If the patient meets the predefined discharge criteria, antibiotic treatment is continued orally at home. Primary outcome is the rate of complications at 1-year follow-up. An independent adjudication committee will assess all complications and their relation to the allocated treatment. Secondary outcomes include, but are not limited to, delayed appendectomies, QoL, pain and (in)direct costs. The primary outcome will be analysed both according to the intention-to-treat principle and the per-protocol principle, and is presented with a one-sided 97.5% CI. We will use multiple logistic and linear regression for binary and continuous outcomes, respectively, to adjust for stratification factors. Ethics and dissemination The protocol has been approved by the Medical Ethics Review Committee of the Academic Medical Center, Amsterdam. Data monitoring is performed by an independent institute and a Data Safety Monitoring Board has been assigned. Results will be presented in peer-reviewed academic journals and at (international) conferences. Trial registration number NCT02848820; NTR5977; Pre-results. PMID:29146647

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

PubMed

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

2012-03-01

The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Challenges and Potential Solutions to Meeting Accrual Goals in a Phase II Chemoprevention Trial for Prostate Cancer

PubMed Central

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

2011-01-01

Objective The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. Methods We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Results Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. Conclusion A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. PMID:22101219

A Consensus-Based Interpretation of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure Trial.

PubMed

Chesnut, Randall M; Bleck, Thomas P; Citerio, Giuseppe; Classen, Jan; Cooper, D James; Coplin, William M; Diringer, Michael N; Grände, Per-Olof; Hemphill, J Claude; Hutchinson, Peter J; Le Roux, Peter; Mayer, Stephan A; Menon, David K; Myburgh, John A; Okonkwo, David O; Robertson, Claudia S; Sahuquillo, Juan; Stocchetti, Nino; Sung, Gene; Temkin, Nancy; Vespa, Paul M; Videtta, Walter; Yonas, Howard

2015-11-15

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Intention to treat (ITT) analysis as reported in orthodontic randomized controlled trials-evaluations of methodology and recommendations for the accurate use of ITT analysis and handling dropouts.

PubMed

Bondemark, Lars; Abdulraheem, Salem

2017-10-21

To systematically evaluate in five orthodontic journals how many randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to assess the methodological quality of the ITT analysis, and finally, to demonstrate in an academic way how outcomes can be affected when not implementing the ITT analysis. A search of the database, Medline, was performed via PubMed for publication type 'randomized controlled trial' published for each journal between 1 January 2013 and 30 April 2017. The five orthodontic journals assessed were the American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research. Two independent reviewers assessed each RCT to determine whether the trial reported an ITT or not or if a per-protocol analysis was accomplished. The initial search generated 137 possible trials. After applying the inclusion and exclusion criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%) either reported an ITT analysis in the text and/or supported the ITT by flow diagrams or tables. However, six RCTs applied and reported the ITT analysis correctly, while the majority performed a per-protocol analysis instead. Nearly all the trials that applied the ITT analysis incorrectly analysed the results using a per-protocol analysis, and thus, overestimating the results and/or having a reduced sample size which then could produce a diminished statistical power. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Practical issues regarding implementing a randomized clinical trial in a homeless population: strategies and lessons learned.

PubMed

Ojo-Fati, Olamide; Joseph, Anne M; Ig-Izevbekhai, Jed; Thomas, Janet L; Everson-Rose, Susan A; Pratt, Rebekah; Raymond, Nancy; Cooney, Ned L; Luo, Xianghua; Okuyemi, Kolawole S

2017-07-05

There is a critical need for objective data to guide effective health promotion and care for homeless populations. However, many investigators exclude homeless populations from clinical trials due to practical concerns about conducting research with this population. This report is based on our experience and lessons learned while conducting two large NIH-funded randomized controlled trials targeting smoking cessation among persons who are homeless. The current report also addresses challenges when conducting clinical trials among homeless populations and offers potential solutions. Homeless individuals face several challenges including the need to negotiate daily access to food, clothing, and shelter. Some of the critical issues investigators encounter include recruitment and retention obstacles; cognitive impairment, mental health and substance abuse disorders; transportation and scheduling challenges; issues pertaining to adequate study compensation; the need for safety protocols for study staff; and issues related to protecting the wellbeing of these potentially vulnerable adults. Anticipating realistic conditions in which to conduct studies with participants who are homeless will help investigators to design efficient protocols and may improve the feasibility of conducting clinical trials involving homeless populations and the quality of the data collected by the researchers. ClinicalTrials.gov, ID: NCT00786149 . Registered on 5 November 2008; ClinicalTrials.gov, ID: NCT01932996 . Registered on 20 November 2014.

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics.

PubMed

Garner, Alan A; Fearnside, Michael; Gebski, Val

2013-09-14

The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. ClinicalTrials.gov: NCT00112398.

A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal lymphomas.

PubMed

Childress, Michael O; Ramos-Vara, José A; Ruple, Audrey

2016-11-01

OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas. DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial. ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment. PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO). The primary outcome of interest was progression-free survival time. Veterinary caregivers and assessors of outcome were not blinded to treatment assignment. Treatment assignment was concealed from the owners of study dogs prior to enrollment, but was revealed after written informed consent was provided. RESULTS The trial was terminated early because of slow enrollment. The 40 dogs successfully enrolled in the study were randomly assigned to the L-CHOP (n = 18) or L-CHO (22) group; results for all 40 dogs were analyzed with respect to the primary outcome. Median progression-free survival time was 142.5 days for dogs receiving L-CHO and 292 days for dogs receiving L-CHOP (hazard ratio, 1.79; 95% confidence interval, 0.85 to 3.75). Serious adverse events were more common among dogs receiving L-CHO. However, this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE The exclusion of prednisone from the L-CHOP protocol did not appear to result in improved progression-free survival time for dogs with peripheral nodal lymphomas. However, the present trial was likely underpowered to detect a clinically meaningful difference in progression-free survival time between groups.

The Active for Life Year 5 (AFLY5) school-based cluster randomised controlled trial protocol: detailed statistical analysis plan.

PubMed

Lawlor, Debbie A; Peters, Tim J; Howe, Laura D; Noble, Sian M; Kipping, Ruth R; Jago, Russell

2013-07-24

The Active For Life Year 5 (AFLY5) randomised controlled trial protocol was published in this journal in 2011. It provided a summary analysis plan. This publication is an update of that protocol and provides a detailed analysis plan. This update provides a detailed analysis plan of the effectiveness and cost-effectiveness of the AFLY5 intervention. The plan includes details of how variables will be quality control checked and the criteria used to define derived variables. Details of four key analyses are provided: (a) effectiveness analysis 1 (the effect of the AFLY5 intervention on primary and secondary outcomes at the end of the school year in which the intervention is delivered); (b) mediation analyses (secondary analyses examining the extent to which any effects of the intervention are mediated via self-efficacy, parental support and knowledge, through which the intervention is theoretically believed to act); (c) effectiveness analysis 2 (the effect of the AFLY5 intervention on primary and secondary outcomes 12 months after the end of the intervention) and (d) cost effectiveness analysis (the cost-effectiveness of the AFLY5 intervention). The details include how the intention to treat and per-protocol analyses were defined and planned sensitivity analyses for dealing with missing data. A set of dummy tables are provided in Additional file 1. This detailed analysis plan was written prior to any analyst having access to any data and was approved by the AFLY5 Trial Steering Committee. Its publication will ensure that analyses are in accordance with an a priori plan related to the trial objectives and not driven by knowledge of the data. ISRCTN50133740.

Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols.

PubMed

Charvet, Leigh E; Kasschau, Margaret; Datta, Abhishek; Knotkova, Helena; Stevens, Michael C; Alonzo, Angelo; Loo, Colleen; Krull, Kevin R; Bikson, Marom

2015-01-01

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user's capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population's level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Research ethics board approval for an international thromboprophylaxis trial.

PubMed

Lutz, Kristina; Wilton, Kelly; Zytaruk, Nicole; Julien, Lisa; Hall, Richard; Harvey, Johanne; Skrobik, Yoanna; Vlahakis, Nicholas; Meade, Laurie; Matte, Andrea; Meade, Maureen; Burns, Karen; Albert, Martin; Cash, Bronwyn Barlow; Vallance, Shirley; Klinger, James; Heels-Ansdell, Diane; Cook, Deborah

2012-06-01

Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial. We generated survey items through literature review and investigators' discussions, creating 4 domains: respondent and institutional demographics, the REB application process, and alternate consent models. We conducted a document analysis that involved duplicate assessment of themes from REB critique of the protocol and informed consent forms (ICF). Approval was granted from 65 REB institutions, requiring 58 unique applications. We analyzed 44 (75.9%) of 58 documents and surveys. Survey respondents completing the applications had 8 (5-12) years of experience; 77% completed 4 or more REB applications in previous 5 years. Critical care personnel were represented on 54% of REBs. The time to approval was a median (interquartile range) of 75 (42, 150) days, taking longer for sites with national research consortium membership (89.1 vs 31.0 days, P = .03). Document analysis of the application process and ICF yielded 5 themes: methodology, data management, consent procedures, cataloguing, and miscellaneous. Protocol-specific themes focused on trial implementation, external critiques, and budget. The only theme specific to the ICF was risks and benefits. The most frequent comments on the protocol and ICF were about methodology and miscellaneous issues; ICF comments also addressed study risks and benefits. More studies on methods to enhance efficiency and consistency of the REB approval processes for clinical trials are needed while still maintaining high ethical standards. Copyright © 2012 Elsevier Inc. All rights reserved.

Antenatal peer support workers and initiation of breast feeding: cluster randomised controlled trial.

PubMed

MacArthur, Christine; Jolly, Kate; Ingram, Lucy; Freemantle, Nick; Dennis, Cindy-Lee; Hamburger, Ros; Brown, Julia; Chambers, Jackie; Khan, Khalid

2009-01-30

To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. Cluster randomised controlled trial. Community antenatal clinics in one primary care trust in a multiethnic, deprived population. 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 weeks' gestation within the antenatal clinic or at home. The trained peer support workers were of similar ethnic and sociodemographic backgrounds to their clinic population. Initiation of breast feeding obtained from computerised maternity records of the hospitals where women from the primary care trust delivered. The sample was multiethnic, with only 9.4% of women being white British, and 70% were in the lowest 10th for deprivation. Most of the contacts with peer support workers took place in the antenatal clinics. Data on initiation of breast feeding were obtained for 2398 of 2511 (95.5%) women (1083/1140 intervention and 1315/1371 controls). The groups did not differ for initiation of breast feeding: 69.0% (747/1083) in the intervention group and 68.1% (896/1315) in the control groups; cluster adjusted odds ratio 1.11 (95% confidence interval 0.87 to 1.43). Ethnicity, parity, and mode of delivery independently predicted initiation of breast feeding, but randomisation to the peer support worker service did not. A universal service for initiation of breast feeding using peer support workers provided within antenatal clinics serving a multiethnic, deprived population was ineffective in increasing initiation rates. Current Controlled Trials ISRCTN16126175.

Macrolides for diffuse panbronchiolitis.

PubMed

Yang, Ming; Dong, Bi Rong; Lu, Jing; Lin, Xiufang; Wu, Hong Mei

2010-12-08

Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to April 2010), EMBASE (1974 to April 2010), Chinese Biomedical Literature Database (CBM) (1978 to April 2010), China National Knowledge Infrastructure (CNKI) (1974 to April 2010), KoreaMed (1997 to April 2010) and Database of Japana Centra Revuo Medicina (1983 to April 2010). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to the Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.

Macrolides for diffuse panbronchiolitis.

PubMed

Lin, Xiufang; Lu, Jing; Yang, Ming; Dong, Bi Rong; Wu, Hong Mei

2015-01-25

Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched CENTRAL (2014, Issue 6), MEDLINE (1966 to July week 1, 2014), EMBASE (1974 to July 2014), Chinese Biomedical Literature Database (CBM) (1978 to July 2014), China National Knowledge Infrastructure (CNKI) (1974 to July 2014), KoreaMed (1997 to July 2014) and Database of Japana Centra Revuo Medicina (1983 to July 2014). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to The Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. This review was previously published in 2010 and 2013. For this 2014 update, we identified no new trials for inclusion or exclusion. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.

Update to a protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Kadir, Bryar; Garfield, Kirsty; Lyons, Ronan A; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence, and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. In addition, this paper describes an update that has been made to the protocol for the PLAN-A feasibility cluster randomised controlled trial. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer supporters. Approximately 15% of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. The study will provide the information necessary to design a fully powered trial should PLAN-A demonstrate evidence of promise. This paper describes an update to the protocol for the PLAN-A feasibility cluster randomised controlled trial related to the data-linkage component. ISRCTN12543546.

Preliminary clinical trial of immunotherapy for malignant glioma.

PubMed

Ingram, M; Shelden, C H; Jacques, S; Skillen, R G; Bradley, W G; Techy, G B; Freshwater, D B; Abts, R M; Rand, R W

1987-10-01

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Treat-to-target trials in diabetes.

PubMed

Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K

2014-03-01

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

Kinesiology tape mediates soccer-simulated and local peroneal fatigue in soccer players.

PubMed

Farquharson, Claire; Greig, Matt

2017-01-01

To investigate the efficacy of kinesiology taping in mediating the influence of fatigue on ankle sprain risk, 12 male soccer players completed single-leg dynamic balance trials pre- and post-exercise (soccer-specific protocol, isokinetic ankle inversion/eversion protocol) in each of three counter-balanced taping conditions (no tape, zinc oxide tape ZO, kinesiology tape KT). Balance was quantified as the overall stability index (OSI) and directional stability indices of platform deflection. Soccer-specific fatigue only increased OSI in the no tape condition (p = 0.03), with ZO and KT trials negating a fatigue affect. Localized fatigue increased OSI in the no tape (p = 0.01) and ZO (p = 0.05) trials, with no increase in the KT trial. A similar pattern was observed in medio-lateral and anterio-posterior balance indices. KT mediates soccer-simulated and local peroneal fatigue, with practical implications for epidemiological observations of increased injury risk during the latter stages of match play.

Digital pathology in nephrology clinical trials, research, and pathology practice.

PubMed

Barisoni, Laura; Hodgin, Jeffrey B

2017-11-01

In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

Transdiagnostic computerised cognitive behavioural therapy for depression and anxiety: A systematic review and meta-analysis.

PubMed

Newby, Jill M; Twomey, Conal; Yuan Li, Susan Shi; Andrews, Gavin

2016-07-15

An increasing number of computerised transdiagnostic cognitive behavioural therapy programs (TD-cCBT) have been developed in the past decade, but there are no meta-analyses to explore the efficacy of these programs, nor moderators of the effects. The current meta-analysis focused on studies evaluating TD-cCBT interventions to examine their effects on anxiety, depression and quality of life (QOL). Results from 17 RCTs showed computerised TD-cCBT outperformed control conditions on all outcome measures at post-treatment, with large effect sizes for depression (g's=.84), and medium effect sizes for anxiety (g=.78) and QOL (g=.48). RCT quality was generally good, although heterogeneity was moderate to high. Further analyses revealed that studies comparing TD-cCBT to waitlist controls had the largest differences (g=.93) compared to active (g=.59) and usual care control groups (g=.37) on anxiety outcomes, but there was no influence of control group subtype on depression outcomes. Treatment length, symptom target (mixed versus anxiety only), treatment design (standardised versus tailored), and therapist experience (students versus qualified therapists) did not influence the results. Preliminary evidence from 4 comparisons with disorder-specific treatments suggests transdiagnostic treatments are as effective for reducing anxiety, and there may be small but superior outcomes for TD-cCBT programs for reducing depression (g=.21) and improving QOL (g=.21) compared to disorder-specific cCBT. These findings show that TD-cCBT programs are efficacious, and have comparable effects to disorder-specific cCBT programs. Copyright © 2016 Elsevier B.V. All rights reserved.

Quality Assurance for Clinical Trials

PubMed Central

Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

2013-01-01

Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics

PubMed Central

2013-01-01

Background The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. Methods This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Results Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. Conclusion This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. Trial Registration ClinicalTrials.gov: NCT00112398 PMID:24034628

Improved Blood Biomarkers but No Cognitive Effects from 16 Weeks of Multivitamin Supplementation in Healthy Older Adults

PubMed Central

Harris, Elizabeth; Macpherson, Helen; Pipingas, Andrew

2015-01-01

Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind, placebo-controlled trial, healthy women (n = 68) and men (n = 48) aged 55–65 years were supplemented daily for 16 weeks with women’s and men’s formula multivitamin supplements. Assessments at baseline and post-supplementation included computerised cognitive tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements were observed after supplementation with either formula; however, several significant improvements were observed in blood biomarkers including increased levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in women; reduced homocysteine and marginally reduced oxidative stress in men; as well as improvements to the lipid profile in men. In healthy older people, multivitamin supplementation improved a number of blood biomarkers that are relevant to cognition, but these biomarker changes were not accompanied by improved cognitive function. PMID:25996285

The use of repetitive transcranial magnetic stimulation for modulating craving and addictive behaviours: a critical literature review of efficacy, technical and methodological considerations.

PubMed

Grall-Bronnec, M; Sauvaget, A

2014-11-01

Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic intervention for the treatment of addiction. This critical review aims to summarise the recent developments with respect to the efficacy of rTMS for all types of addiction and related disorders (including eating disorders), and concentrates on the associated methodological and technical issues. The bibliographic search consisted of a computerised screening of the Medline and ScienceDirect databases up to December 2013. Criteria for inclusion were the target problem was an addiction, a related disorder, or craving; the intervention was performed using rTMS; and the study was a clinical trial. Of the potential 638 articles, 18 met the criteria for inclusion. Most of these (11 of the 18) supported the efficacy of rTMS, especially in the short term. In most cases, the main assessment criterion was the measurement of craving using a Visual Analogue Scale. The results are discussed with respect to the study limitations and, in particular, the many methodological and technical discrepancies that were identified. Key recommendations are provided.

Advice to stay active as a single treatment for low back pain and sciatica.

PubMed

Hilde, G; Hagen, K B; Jamtvedt, G; Winnem, M

2002-01-01

Low back pain is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for low back pain and sciatica. To assess the effects of advice to stay active as single treatment for patients with low back pain. Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. We included all randomised trials or quasi-randomised trials where the study population consisted of adult patients with low back pain or sciatica, in which one comparison group was advised to stay active. The main outcomes of interest were pain, functional status, recovery and return to work. Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. Four trials, with a total of 491 patients, were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of patients with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for patients with sciatic syndrome, and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for patients with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. The best available evidence suggests that advice to stay active alone has small beneficial effects for patients with acute simple low back pain, and little or no effect for patients with sciatica. There is no evidence that advice to stay active is harmful for either acute low back pain or sciatica. If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise people with acute low back pain and sciatica to stay active. These conclusions are based on single trials.

WITHDRAWN: Advice to stay active as a single treatment for low-back pain and sciatica.

PubMed

Hilde, G; Hagen, K B; Jamtvedt, G; Winnem, M

2007-07-18

Low back pain is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for low back pain and sciatica. To assess the effects of advice to stay active as single treatment for patients with low back pain. Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. We included all randomised trials or quasi-randomised trials where the study population consisted of adult patients with low back pain or sciatica, in which one comparison group was advised to stay active. The main outcomes of interest were pain, functional status, recovery and return to work. Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. Four trials, with a total of 491 patients, were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of patients with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for patients with sciatic syndrome, and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for patients with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. The best available evidence suggests that advice to stay active alone has small beneficial effects for patients with acute simple low back pain, and little or no effect for patients with sciatica. There is no evidence that advice to stay active is harmful for either acute low back pain or sciatica. If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise people with acute low back pain and sciatica to stay active. These conclusions are based on single trials.

Intravenous Immunoglobulin in the Therapeutic Armamentarium of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

PubMed Central

Sakthiswary, Rajalingham; D’Cruz, David

2014-01-01

Abstract Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants. IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221–0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1–41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels. PMID:25310743

Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis.

PubMed

Sakthiswary, Rajalingham; D'Cruz, David

2014-10-01

Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels.

Banked preterm versus banked term human milk to promote growth and development in very low birth weight infants.

PubMed

Dempsey, Eugene; Miletin, Jan

2010-06-16

Human milk banking has been available in many countries for the last three decades. The milk provided from milk banking is predominantly term breast milk, but some milk banks provide preterm breast milk. There are a number of differences between donor term and donor preterm human milk. To determine the effect of banked preterm milk compared with banked term milk regarding growth and developmental outcome in very low birth weight infants (infants weighing less than 1500 g). We used the standard methods of the Cochrane Neonatal Review Group, including a search of the Cochrane Neonatal Group specialized register and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, January 2010). We searched the computerised bibliographic databases MEDLINE (1966 to February 2010), EMBASE (1988 to February 2010) and Web of Science (1975 to February 2010). We searched reference lists of all selected articles, review articles and the Oxford Database of Perinatal Trials. We also searched abstracts from neonatal and pediatric meetings (PAS electronic version from 2000 to 2009, ESPR hand search from 2000 to 2009). We applied no language restrictions. Randomised and quasi-randomised trials comparing banked donor preterm milk with banked donor term milk regarding growth and developmental outcomes in very low birth weight infants We planned to perform assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up. We planned to evaluate treatment effect using a fixed-effect model using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We planned an evaluation of heterogeneity. No studies met the inclusion criteria. There are no randomised trials that compare preterm banked milk to banked term milk to promote growth and development in very low birth weight infants.

Time Regained: When People Stop a Physical Activity Program, How Does Their Time Use Change? A Randomised Controlled Trial

PubMed Central

Gomersall, Sjaan; Maher, Carol; English, Coralie; Rowlands, Alex; Olds, Tim

2015-01-01

The aim of this study was to investigate how previously inactive adults who had participated in a structured, partly supervised 6-week exercise program restructured their time budgets when the program ended. Using a randomised controlled trial design, 129 previously inactive adults were recruited and randomly allocated to one of three groups: a Moderate or Extensive six-week physical activity intervention (150 and 300 additional minutes of exercise per week, respectively) or a Control group. Additional physical activity was accumulated through both group and individual exercise sessions with a wide range of activities. Use of time and time spent in energy expenditure zones was measured using a computerised 24-h self-report recall instrument, the Multimedia Activity Recall for Children and Adults, and accelerometry at baseline, mid- and end-program and at 3- and 6-months follow up. At final follow up, all significant changes in time use domains had returned to within 20 minutes of baseline levels (Physical Activity 1-2 min/d, Active Transport 3-9 min/d, Self-Care 0-2 min/d, Television/Videogames 13-18 min/d in the Moderate and Extensive group, relative to Controls, respectively, p>0.05). Similarly, all significant changes in time spent in the moderate energy expenditure zone had returned to within 1-3 min/d baseline levels (p>0.05), however time spent in vigorous physical activity according to accelerometry estimates remained elevated, although the changes were small in magnitude (1 min/d in the Moderate and Extensive groups, relative to Controls, p=0.01). The results of this study demonstrate strong recidivist patterns in physical activity, but also in other aspects of time use. In designing and determining the effectiveness of exercise interventions, future studies would benefit from considering the whole profile of time use, rather than focusing on individual activities. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12610000248066 PMID:26023914

A systematic review of randomised controlled trials of the effects of warmed irrigation fluid on core body temperature during endoscopic surgeries.

PubMed

Jin, Yinghui; Tian, Jinhui; Sun, Mei; Yang, Kehu

2011-02-01

The purpose of this systematic review was to establish whether warmed irrigation fluid temperature could decrease the drop of body temperature and incidence of shivering and hypothermia. Irrigation fluid, which is used in large quantities during endoscopic surgeries at room temperature, is considered to be associated with hypothermia and shivering. It remains controversial whether using warmed irrigation fluid to replace room-temperature irrigation fluid will decrease the drop of core body temperature and the occurrence of hypothermia. A comprehensive search (computerised database searches, footnote chasing, citation chasing) was undertaken to identify all the randomised controlled trials that explored temperature of irrigation fluid in endoscopic surgery. An approach involving meta-analysis was used. We searched PubMed, EMBASE, Cochrane Library, SCI, China academic journals full-text databases, Chinese Biomedical Literature Database, Chinese scientific journals databases and Chinese Medical Association Journals for trials that meet the inclusion criteria. Study quality was assessed using standards recommended by Cochrane Library Handbook 5.0.1. Disagreement was resolved by consensus. Thirteen randomised controlled trials including 686 patients were identified. The results showed that room-temperature irrigation fluid caused a greater drop of core body temperature in patients, compared to warmed irrigation fluid (p < 0.00001; I(2) = 85%). The occurrence of shivering [odds ratio (OR) 5.13, 95% CI: 2.95-10.19, p < 0.00001; I(2) = 0%] and hypothermia (OR 22.01, 95% CI: 2.03-197.08, p = 0.01; I(2) = 64%) in the groups having warmed irrigation fluid were lower than the group of studies having room-temperature fluid. In endoscopic surgeries, irrigation fluid is recommended to be warmed to decrease the drop of core body temperature and the risk of perioperative shivering and hypothermia. Warming irrigating fluid should be considered standard practice in all endoscopic surgeries. © 2011 Blackwell Publishing Ltd.

Non-nutritive sucking for gastro-oesophageal reflux disease in preterm and low birth weight infants.

PubMed

Psaila, Kim; Foster, Jann P; Richards, Robyn; Jeffery, Heather E

2014-10-15

Gastro-oesophageal reflux (GOR) is commonly diagnosed in the neonatal population (DiPietro 1994), and generally causes few or no symptoms (Vandenplas 2009). Conversely, gastro-oesophageal reflux disease (GORD) refers to GOR that causes troublesome symptoms with or without complications such as damage to the oesophagus (Vandenplas 2009). Currently there is no evidence to support the range of measures recommended to help alleviate acid reflux experienced by infants. Non-nutritive sucking (NNS) has been used as an intervention to modulate neonatal state behaviours through its pacifying effects such as decrease infant fussiness and crying during feeds (Boiron 2007; Pickler 2004). To determine if NNS reduces GORD in preterm infants (less than 37 weeks' gestation) and low birth weight (less than 2500 g) infants, three months of age and less, with signs or symptoms suggestive of GORD, or infants with a diagnosis of GORD. We performed computerised searches of the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 9, 2013), MEDLINE (1966 to September 2013), CINAHL (1982 to September 2013), and EMBASE (1988 to September 2013). We applied no language restrictions. Controlled trials using random or quasi-random allocation of preterm infants (less than 37 weeks' gestation) and low birth weight (less than 2500 g) infants three months of age and less with signs or symptoms suggestive of GORD, or infants with a diagnosis of GORD. We included studies reported only by abstracts, and cluster and cross-over randomised trials. Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data. We identified two studies from the initial search. After further review, we excluded both studies. We identified no studies examining the effects of NNS for GORD in preterm and low birth weight infants There was insufficient evidence to determine the effectiveness of NNS for GORD. Adequately powered RCTs on the effect of NNS in preterm and low birth weight infants diagnosed with GORD are required.

Computerised lung sound monitoring to assess effectiveness of chest physiotherapy and secretion removal: a feasibility study.

PubMed

Ntoumenopoulos, G; Glickman, Y

2012-09-01

To explore the feasibility of computerised lung sound monitoring to evaluate secretion removal in intubated and mechanically ventilated adult patients. Before and after observational investigation. Intensive care unit. Fifteen intubated and mechanically ventilated adult patients receiving chest physiotherapy. Chest physiotherapy included combinations of standard closed airway suctioning, saline lavage, postural drainage, chest wall vibrations, manual-assisted cough and/or lung hyperinflation, dependent upon clinical indications. Lung sound amplitude at peak inspiration was assessed using computerised lung sound monitoring. Measurements were performed immediately before and after chest physiotherapy. Data are reported as mean [standard deviation (SD)], mean difference and 95% confidence intervals (CI). Significance testing was not performed due to the small sample size and the exploratory nature of the study. Fifteen patients were included in the study [11 males, four females, mean age 65 (SD 14) years]. The mean total lung sound amplitude at peak inspiration decreased two-fold from 38 (SD 59) units before treatment to 17 (SD 19) units after treatment (mean difference 22, 95% CI of difference -3 to 46). The mean total lung sound amplitude from the lungs of patients with a large amount of secretions (n=9) was over four times 'louder' than the lungs of patients with a moderate or small amount of secretions (n=6) [56 (SD 72) units vs 12 (13) units, respectively; mean difference -44, 95% CI of difference -100 to 11]. The mean total lung sound amplitude decreased in the group of 'loud' right and left lungs (n=15) from 37 (SD 36) units before treatment to 15 (SD 13) units after treatment (mean difference 22, 95% CI of difference 6 to 38). Computerised lung sound monitoring in this small group of patients demonstrated a two-fold decrease in lung sound amplitude following chest physiotherapy. Subgroup analysis also demonstrated decreasing trends in lung sound amplitude in the group of 'loud' lungs following chest physiotherapy. Due to the small sample size and large SDs with high variability in the lung sound amplitude measurements, significance testing was not reported. Further investigation is needed in a larger sample of patients with more accurate measurement of sputum wet weight in order to distinguish between secretion-related effects and changes due to other factors such as airflow rate and pattern. Copyright © 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Lungtech, a phase II EORTC trial of SBRT for centrally located lung tumours - a clinical physics perspective.

PubMed

Lambrecht, Marie; Melidis, Christos; Sonke, Jan-Jakob; Adebahr, Sonja; Boellaard, Ronald; Verheij, Marcel; Guckenberger, Matthias; Nestle, Ursula; Hurkmans, Coen

2016-01-20

The EORTC has launched a phase II trial to assess safety and efficacy of SBRT for centrally located NSCLC: The EORTC 22113-08113-Lungtech trial. Due to neighbouring critical structures, these tumours remain challenging to treat. To guarantee accordance to protocol and treatment safety, an RTQA procedure has been implemented within the frame of the EORTC RTQA levels. These levels are here expanded to include innovative tools beyond protocol compliance verification: the actual dose delivered to each patient will be estimated and linked to trial outcomes to enable better understanding of dose related response and toxicity. For trial participation, institutions must provide a completed facility questionnaire and beam output audit results. To insure ability to comply with protocol specifications a benchmark case is sent to all centres. After approval, institutions are allowed to recruit patients. Nonetheless, each treatment plan will be prospectively reviewed insuring trial compliance consistency over time. As new features, patient's CBCT images and applied positioning corrections will be saved for dose recalculation on patient's daily geometry. To assess RTQA along the treatment chain, institutions will be visited once during the time of the trial. Over the course of this visit, end-to-end tests will be performed using the 008ACIRS-breathing platform with two separate bodies. The first body carries EBT3 films and an ionization chamber. The other body newly developed for PET- CT evaluation is fillable with a solution of high activity. 3D or 4D PET-CT and 4D-CT scanning techniques will be evaluated to assess the impact of motion artefacts on target volume accuracy. Finally, a dosimetric evaluation in static and dynamic conditions will be performed. Previous data on mediastinal toxicity are scarce and source of cautiousness for setting-up SBRT treatments for centrally located NSCLC. Thanks to the combination of documented patient related outcomes and CBCT based dose recalculation we expect to provide improved models for dose response and dose related toxicity. We have developed a comprehensive RTQA model for trials involving modern radiotherapy. These procedures could also serve as examples of extended RTQA for future radiotherapy trials involving quantitative use of PET and tumour motion.

Does a fall prevention educational programme improve knowledge and change exercise prescribing behaviour in health and exercise professionals? A study protocol for a randomised controlled trial.

PubMed

Tiedemann, A; Sturnieks, D L; Hill, A-M; Lovitt, L; Clemson, L; Lord, S R; Harvey, L; Sherrington, C

2014-11-19

Falling in older age is a serious and costly problem. At least one in three older people fall annually. Although exercise is recognised as an effective fall prevention intervention, low numbers of older people engage in suitable programmes. Health and exercise professionals play a crucial role in addressing fall risk in older adults. This trial aims to evaluate the effect of participation in a fall prevention educational programme, compared with a wait-list control group, on health and exercise professionals' knowledge about fall prevention and the effect on fall prevention exercise prescription behaviour and confidence to prescribe the exercises to older people. A randomised controlled trial involving 220 consenting health and exercise professionals will be conducted. Participants will be individually randomised to an intervention group (n=110) to receive an educational workshop plus access to internet-based support resources, or a wait-list control group (n=110). The two primary outcomes, measured 3 months after randomisation, are: (1) knowledge about fall prevention and (2) self-perceived change in fall prevention exercise prescription behaviour. Secondary outcomes include: (1) participants' confidence to prescribe fall prevention exercises; (2) the proportion of people aged 60+ years seen by trial participants in the past month who were prescribed fall prevention exercise; and (3) the proportion of fall prevention exercises prescribed by participants to older people in the past month that comply with evidence-based guidelines. Outcomes will be measured with a self-report questionnaire designed specifically for the trial. The trial protocol was approved by the Human Research Ethics Committee, The University of Sydney, Australia. Trial results will be disseminated via peer reviewed journals, presentations at international conferences and participants' newsletters. Trial protocol was registered with the Australian and New Zealand Clinical Trials Registry (Number ACTRN12614000224628) on 3 March 2014. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Devos, Laura; Thecua, Elise; Vicentini, Claire; Mortier, Laurent; Mordon, Serge

2017-09-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol) is sufficient (respectively, excessive) to destroy actinic keratosis cells. Lasers Surg. Med. 49:686-697, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Re-evaluation of broiler carcass scalding protocols for impact on the recovery of Campylobacter from breast skin after defeathering

USDA-ARS?s Scientific Manuscript database

This research re-evaluated the impact of scalding protocols on the recovery of Campylobacter from breast skin following defeathering after preliminary processing trials detected Campylobacter from breast skin for 4/8 carcasses that had vents plugged and sutured prior to scalding. Published research...

Resting blood pressure differentially predicts time course in a tonic pain experiment.

PubMed

Horing, Bjoern; McCubbin, James A; Moore, Dewayne; Muth, Eric R

2016-10-01

Resting blood pressure (BP) shows a negative relationship with pain sensitivity (BP-related hypoalgesia). In chronic pain conditions, this relationship is inverted. The precise mechanisms responsible for the inversion are unknown. Using a tonic pain protocol, we report findings closely resembling this inversion in healthy participants. Resting BP and state measures of anxiety and mood were assessed from 33 participants (21 female). Participants then immersed their dominant hand in painfully hot water (47 °C) for five trials of 1-min duration, with 30-s intertrial intervals. Throughout the trials, participants continually registered their pain. After a 35-min intermission, the trial sequence was repeated. A disassociation of the negative relationship of resting systolic BP (as per Trial 1) was found using hierarchical linear modeling (p < .001, R(2)  = .07). The disassociation unfolds over each consecutive trial, with an increasingly positive relationship. In Sequence 2, the initially negative relationship is almost completely absent. Furthermore, the association of BP and pain was found to be moderated by anxiety, such that only persons with low anxiety exhibited BP hypoalgesia. Our findings expand the existing literature by incorporating anxiety as a moderator of BP hypoalgesia. Furthermore, the protocol emulates the changing relationship between BP and pain observed in chronic pain patients. The protocol has potential as a model for chronic pain; however, future research should determine if similar physiological systems are involved. The finding holds potential diagnostic or prognostic relevance for certain clinical pain conditions, especially those involving dysfunction of the descending modulation of pain. © 2016 Society for Psychophysiological Research.

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Thomson, Claire; Doré, Caroline J; Cro, Suzie; Round, Jeff; Molloy, Andrew; Davies, Mark; Karski, Michael; Kim, Louise; Cooke, Paul

2016-01-01

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555. PMID:27601503

Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401.

PubMed

Hurria, Arti; Cirrincione, Constance T; Muss, Hyman B; Kornblith, Alice B; Barry, William; Artz, Andrew S; Schmieder, Linda; Ansari, Rafat; Tew, William P; Weckstein, Douglas; Kirshner, Jeffrey; Togawa, Kayo; Hansen, Kurt; Katheria, Vani; Stone, Richard; Galinsky, Ilene; Postiglione, John; Cohen, Harvey Jay

2011-04-01

Factors captured in a geriatric assessment can predict morbidity and mortality in older adults, but are not routinely measured in cancer clinical trials. This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting. Patients age ≥ 65 with cancer, who enrolled on cooperative group cancer trials, were eligible to enroll on Cancer and Leukemia Group B (CALGB) 360401. They completed a geriatric assessment tool before initiation of protocol therapy, consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal resources and time by healthcare providers. The assessment measures functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance. Patient satisfaction with the tool was captured. Of the 93 patients who enrolled in this study, five (5%) met criteria for cognitive impairment and three did not complete the cognitive screen, leaving 85 assessable patients (median age, 72 years). The median time to complete the geriatric assessment tool was 22 minutes, 87% of patients (n = 74) completed their portion without assistance, 92% (n = 78) were satisfied with the questionnaire length, 95% (n = 81) reported no difficult questions, and 96% (n = 82) reported no upsetting questions. One hundred percent of health care professionals completed their portion. This brief, primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials.

How to design and write a clinical research protocol in Cosmetic Dermatology*

PubMed Central

Bagatin, Ediléia; Miot, Helio A.

2013-01-01

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. PMID:23539006

Acupuncture for patients with Alzheimer's disease: a systematic review protocol

PubMed Central

Zhou, Jing; Peng, Weina; Li, Wang; Liu, Zhishun

2014-01-01

Introduction The aim of this protocol is to provide the methods used to assess the effectiveness and safety of acupuncture for the treatment of patients with Alzheimer's disease. Methods and analysis We will search the following electronic databases: The Cochrane Library, PubMed, Medline, Embase, PsycINFO, Chinese Biomedical Literature Database, Chinese Medical Current Contents and China National Knowledge Infrastructure without restriction of language and publication status. Other sources such as Chinese acupuncture journals and the reference list of selected studies will also be searched. After screening the studies, a meta-analysis of randomised controlled trials will be conducted, if possible. Results expressed as risk ratios for dichotomous data and standardised or weighted mean differences for continuous data, will be used for data synthesis. Dissemination The protocol of this systematic review will be disseminated in a peer-reviewed journal and presented at a relevant conference. Trial registration number PROSPERO CRD42014009619 PMID:25142265

A decision support system and rule-based algorithm to augment the human interpretation of the 12-lead electrocardiogram.

PubMed

Cairns, Andrew W; Bond, Raymond R; Finlay, Dewar D; Guldenring, Daniel; Badilini, Fabio; Libretti, Guido; Peace, Aaron J; Leslie, Stephen J

The 12-lead Electrocardiogram (ECG) has been used to detect cardiac abnormalities in the same format for more than 70years. However, due to the complex nature of 12-lead ECG interpretation, there is a significant cognitive workload required from the interpreter. This complexity in ECG interpretation often leads to errors in diagnosis and subsequent treatment. We have previously reported on the development of an ECG interpretation support system designed to augment the human interpretation process. This computerised decision support system has been named 'Interactive Progressive based Interpretation' (IPI). In this study, a decision support algorithm was built into the IPI system to suggest potential diagnoses based on the interpreter's annotations of the 12-lead ECG. We hypothesise semi-automatic interpretation using a digital assistant can be an optimal man-machine model for ECG interpretation. To improve interpretation accuracy and reduce missed co-abnormalities. The Differential Diagnoses Algorithm (DDA) was developed using web technologies where diagnostic ECG criteria are defined in an open storage format, Javascript Object Notation (JSON), which is queried using a rule-based reasoning algorithm to suggest diagnoses. To test our hypothesis, a counterbalanced trial was designed where subjects interpreted ECGs using the conventional approach and using the IPI+DDA approach. A total of 375 interpretations were collected. The IPI+DDA approach was shown to improve diagnostic accuracy by 8.7% (although not statistically significant, p-value=0.1852), the IPI+DDA suggested the correct interpretation more often than the human interpreter in 7/10 cases (varying statistical significance). Human interpretation accuracy increased to 70% when seven suggestions were generated. Although results were not found to be statistically significant, we found; 1) our decision support tool increased the number of correct interpretations, 2) the DDA algorithm suggested the correct interpretation more often than humans, and 3) as many as 7 computerised diagnostic suggestions augmented human decision making in ECG interpretation. Statistical significance may be achieved by expanding sample size. Copyright © 2017 Elsevier Inc. All rights reserved.

Interventions for the prevention of nutritional rickets in term born children.

PubMed

Lerch, C; Meissner, T

2007-10-17

Nutritional rickets is a disease of growing children leading to bone deformities, bone pain, convulsions or delayed motor development. Today, high-incidence of nutritional rickets is mainly found in low-income countries. To assess the effects of various interventions on the prevention of nutritional rickets in term born children. Studies were obtained from computerised searches of The Cochrane Library, MEDLINE, EMBASE, LILACS and reference lists of relevant articles. We contacted authors of studies or reviews to obtain further studies. Studies were included if they were randomised controlled clinical trials, controlled clinical trials or prospective cohort studies comparing any intervention for the prevention of nutritional rickets in term born children with placebo or no intervention. Minimum duration of the intervention was three months for children under 12 months or six months for children over 12 months. Two authors independently extracted data and assessed study quality. Authors of studies were contacted to obtain missing information. Four studies enrolled approximately 1700 participants. Trials lasted between nine months to two years. Three studies were randomised controlled trials, two of which showed a cluster randomised design; one trial probably was a controlled trial with researcher controlled group assignment. In children up to three years of age in Turkey, Vitamin D compared to no intervention showed a relative risk of 0.04 (95% confidence interval (CI) 0 to 0.71). Despite a marked non-compliance, a Chinese trial in children up to three years of age comparing a combined intervention of supplementation of vitamin D, calcium and nutritional counseling showed a relative risk of 0.76 (95% CI 0.61 to 0.95) compared to no intervention. In two studies conducted in older children in China and in France no rickets occurred in both the intervention and control group. There a only few studies on the prevention of nutritional rickets in term born children. Until new data become available, it appears sound to offer preventive measures (vitamin D or calcium) to groups of high risk, like infants and toddlers; children living in Africa, Asia or the Middle East or migrated children from these regions into areas where rickets is not frequent. Due to a marked clinical heterogeneity and the scarcity of data, the main and adverse effects of preventive measures against nutritional rickets should be investigated in different countries, different age groups and in children of different ethnic origin.

PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomography-computerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer.

PubMed

Mehanna, Hisham; McConkey, Chris C; Rahman, Joy K; Wong, Wai-Lup; Smith, Alison F; Nutting, Chris; Hartley, Andrew Gj; Hall, Peter; Hulme, Claire; Patel, Dharmesh K; Zeidler, Sandra Ventorin von; Robinson, Max; Sanghera, Bal; Fresco, Lydia; Dunn, Janet A

2017-04-01

Planned neck dissection (ND) after radical chemoradiotherapy (CRT) for locally advanced nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens show histological evidence of tumour. Consequently, a significant proportion of clinicians still practise planned ND. Fludeoxyglucose positron emission tomography (PET)-computerised tomography (CT) scanning demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. Evidence is sparse and drawn mainly from retrospective single-institution studies, illustrating the need for a prospective randomised controlled trial. To determine the efficacy and cost-effectiveness of PET-CT-guided surveillance, compared with planned ND, in a multicentre, prospective, randomised setting. A pragmatic randomised non-inferiority trial comparing PET-CT-guided watch-and-wait policy with the current planned ND policy in HNSCC patients with locally advanced nodal metastases and treated with radical CRT. Patients were randomised in a 1 : 1 ratio. Primary outcomes were overall survival (OS) and cost-effectiveness [incremental cost per incremental quality-adjusted life-year (QALY)]. Cost-effectiveness was assessed over the trial period using individual patient data, and over a lifetime horizon using a decision-analytic model. Secondary outcomes were recurrence in the neck, complication rates and quality of life. The recruitment of 560 patients was planned to detect non-inferior OS in the intervention arm with a 90% power and a type I error of 5%, with non-inferiority defined as having a hazard ratio (HR) of no higher than 1.50. An intention-to-treat analysis was performed by Cox's proportional hazards model. Thirty-seven head and neck cancer-treating centres (43 NHS hospitals) throughout the UK. Patients with locally advanced nodal metastases of oropharynx, hypopharynx, larynx, oral or occult HNSCC receiving CRT and fit for ND were recruited. Patients randomised to planned ND before or after CRT (control), or CRT followed by fludeoxyglucose PET-CT 10-12 weeks post CRT with ND only if PET-CT showed incomplete or equivocal response of nodal disease (intervention). Balanced by centre, planned ND timing, CRT schedule, disease site and the tumour, node, metastasis stage. In total, 564 patients were recruited (ND arm, n  = 282; and surveillance arm, n  = 282; 17% N2a, 61% N2b, 18% N2c and 3% N3). Eighty-four per cent had oropharyngeal cancer. Seventy-five per cent of tested cases were p16 positive. The median time to follow-up was 36 months. The HR for OS was 0.92 [95% confidence interval (CI) 0.65 to 1.32], indicating non-inferiority. The upper limit of the non-inferiority HR margin of 1.50, which was informed by patient advisors to the project, lies at the 99.6 percentile of this estimate ( p  = 0.004). There were no differences in this result by p16 status. There were 54 NDs performed in the surveillance arm, with 22 surgical complications, and 221 NDs in the ND arm, with 85 complications. Quality-of-life scores were slightly better in the surveillance arm. Compared with planned ND, PET-CT surveillance produced an incremental net health benefit of 0.16 QALYs (95% CI 0.03 to 0.28 QALYs) over the trial period and 0.21 QALYs (95% CI -0.41 to 0.85 QALYs) over the modelled lifetime horizon. Pragmatic randomised controlled trial with a 36-month median follow-up. PET-CT-guided active surveillance showed similar survival outcomes to ND but resulted in considerably fewer NDs, fewer complications and lower costs, supporting its use in routine practice. PET-CT surveillance is cost-effective in the short term, and long-term cost-effectiveness could be addressed in future work. Current Controlled Trials ISRCTN13735240. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 17. See the NIHR Journals Library website for further project information.

Reporting of clinical trials: a review of research funders' guidelines

PubMed Central

Dwan, Kerry; Gamble, Carrol; Williamson, Paula R; Altman, Douglas G

2008-01-01

Background Randomised controlled trials (RCTs) represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. Methods National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. Results Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. Conclusion Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias. Current guidelines need to be updated and include the statement that all primary and secondary outcomes prespecified in the protocol should be fully reported and should not be selected for inclusion in the final report based on their results. PMID:19032743

Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)

PubMed Central

2012-01-01

Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements. PMID:22928744

Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial.

PubMed

Cro, Suzie; Mehta, Saahil; Farhadi, Jian; Coomber, Billie; Cornelius, Victoria

2018-01-01

Essential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition. PREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT. This article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the PREHEAT trial. ISRCTN ISRCTN15744669. Registered 25 February 2015.

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial.

PubMed

Brinkman, Sally A; Johnson, Sarah E; Lawrence, David; Codde, James P; Hart, Michael B; Straton, Judith A Y; Silburn, Sven

2010-10-21

This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms. This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings. ISRCTN24952438.

The PD COMM trial: a protocol for the process evaluation of a randomised trial assessing the effectiveness of two types of SLT for people with Parkinson's disease.

PubMed

Masterson-Algar, Patricia; Burton, Christopher R; Brady, Marian C; Nicoll, Avril; Clarke, Carl E; Rick, Caroline; Hughes, Max; Au, Pui; Smith, Christina H; Sackley, Catherine M

2017-08-29

The PD COMM trial is a phase III multi-centre randomised controlled trial whose aim is to evaluate the effectiveness and cost-effectiveness of two approaches to speech and language therapy (SLT) compared with no SLT intervention (control) for people with Parkinson's disease who have self-reported or carer-reported problems with their speech or voice. Our protocol describes the process evaluation embedded within the outcome evaluation whose aim is to evaluate what happened at the time of the PD COMM intervention implementation and to provide findings that will assist in the interpretation of the PD COMM trial results. Furthermore, the aim of the PD COMM process evaluation is to investigate intervention complexity within a theoretical model of how the trialled interventions might work best and why. Drawing from the Normalization Process Theory and frameworks for implementation fidelity, a mixed method design will be used to address process evaluation research questions. Therapists' and participants' perceptions and experiences will be investigated via in-depth interviews. Critical incident reports, baseline survey data from therapists, treatment record forms and home practice diaries also will be collected at relevant time points throughout the running of the PD COMM trial. Process evaluation data will be analysed independently of the outcome evaluation before the two sets of data are then combined. To date, there are a limited number of published process evaluation protocols, and few are linked to trials investigating rehabilitation therapies. Providing a strong theoretical framework underpinning design choices and being tailored to meet the complex characteristics of the trialled interventions, our process evaluation has the potential to provide valuable insight into which components of the interventions being delivered in PD COMM worked best (and what did not), how they worked well and why. ISRCTN Registry, ISRCTN12421382 . Registered on 18 April 2016.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)

PubMed Central

Williamson, Esther; Lait, Clare; Richmond, Helen; Betteley, Lauren; Lall, Ranjit; Petrou, Stavros; Rees, Sophie; Withers, Emma J; Lamb, Sarah E; Thompson, Alastair M

2018-01-01

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery. Methods This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions. Discussion The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation. Protocol version Version 2.1; dated 11 January 2017 Trial registration number ISRCTN35358984; Pre-results. PMID:29574439

The use of preferred social stimuli as rewards for rhesus macaques in behavioural neuroscience

PubMed Central

Pearce, Bradley; Thiele, Alexander; Rowe, Candy

2017-01-01

Macaques are often motivated to perform in neuroscientific experiments by implementing fluid restriction protocols. Daily access to water is controlled and the monkeys are rewarded with droplets of fluid for performing correct trials in the laboratory. Although these protocols are widely used and highly effective, it is important from a 3Rs perspective to investigate refinements that may help to lessen the severity of the fluid restriction applied. We assessed the use of social stimuli (images of conspecifics) as rewards for four rhesus macaques performing simple cognitive tasks. We found that individual preferences for images of male faces, female perinea and control stimuli could be identified in each monkey. However, using preferred images did not translate into effective motivators on a trial-by-trial basis: animals preferred fluid rewards, even when fluid restriction was relaxed. There was no difference in the monkeys’ performance of a task when using greyscale versus colour images. Based on our findings, we cannot recommend the use of social stimuli, in this form, as a refinement to current fluid restriction protocols. We discuss the potential alternatives and possibilities for future research. PMID:28542356

Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: the design of a factorial randomized controlled trial.

PubMed

Glaser, Nicole S; Ghetti, Simona; Casper, T Charles; Dean, J Michael; Kuppermann, Nathan

2013-09-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the USA and worldwide. The optimal protocol for intravenous (IV) fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of IV fluid infusion and the development of cerebral edema (CE), the most common and the most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and CE have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently, there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (FLuid therapies Under Investigation in DKA) study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically overt CE and long-term neurocognitive outcomes following DKA. © 2013 John Wiley & Sons A/S.

The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

PubMed

Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

2015-07-01

The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

PubMed

Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

2009-01-01

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. KEY ROLES/RESPONSIBILITIES The Protocol Coordinator II: Provides comprehensive clinical and administrative support to the Brain Tumor Trial Collaborative, Neuro-Oncology Branch, NCI, National Institutes of Health Serves as a liaison with Principal Investigators (PIs), the associated study teams and a variety of offices associated with protocol development and approvals Orchestrates meetings with investigators and other key medical staff to identify required support Coordinates the writing and regulatory review processes that occur in tandem, facilitates the bi-directional dialogue and feedback between various teams, and assists investigators and medical writers on the production/revision of clinical research protocols Assists research staff in coordinating/navigating requirements for special circumstances and facilitates access to necessary services Facilitates initiation of intramural research by providing assistance in obtaining required approvals Coordinates with investigators and medical writers to ensure Institutional Review Board (IRB) and Food and Drug Administration (FDA) stipulations are appropriately addressed in a timely manner Provides consultation and assistance for all aspects of the protocol lifecycle including initial Investigational New Drug (IND) submission, IRB submission, continuing review applications, protocol amendments, annual reports, and protocol inactivation with IRB and FDA Tracks a portfolio of protocols through each lifecycle step; processes and tracks appropriate approvals (e.g., IRB, Data and Safety Monitoring Board, Radiation Safety, Office of Protocol Services, etc.) Provides administrative support to Scientific Review Committees (SRC), reviews proposed protocol documents to ensure they are complete, distributes to reviewers, documents meeting minutes, enters data into the IRIS database, facilitates processes to obtain approval to initiate and continue clinical research Creates, maintains and queries an IRB database of approved amendment descriptions Maintains records of the current protocol(s) version, current Informed Consent document(s), FDA Safe to Proceed designation, etc. for each IND Provides expertise in data management including data collection and analysis Develops procedural manuals for clinical trials protocols Participates in quality improvement and assurance involving International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines This position is located at the National Institutes of Health (NIH) in Bethesda, Maryland.

Comparison of V-4 and V-5 Exercise/Oxygen Prebreathe Protocols to Support Extravehicular Activity in Microgravity

NASA Technical Reports Server (NTRS)

Pollock, N. W.; Natoli, M. J.; Vann, R. D.; Gernhardt, M. L.; Conkin, Johnny

2007-01-01

The Prebreathe Reduction Program (PRP) used exercise during oxygen prebreathe to reduce necessary prebreathe time prior to depressurizing to work in a 4.3 psi suit during extravehicular activity (EVA). Initial testing produced a two-hour protocol incorporating ergometry exercise and a 30 min cycle of depress/repress to 10.2 psi where subjects breathed 26.5% oxygen/balance nitrogen (Phase II - 10 min at 75% peak oxygen consumption [VO2 peak] followed by 40 min intermittent light exercise [ILE] [approx. 5.8 mL-per kilogram- per minute], then 50 min of rest). The Phase II protocol (0/45 DCS) was approved for operations and has been used on 40 EVAs, providing significant time savings compared to the standard 4 h resting oxygen prebreathe. The Phase V effort focused on performing all light in-suit exercise. Two oxygen prebreathe protocols were tested sequentially: V-4) 160 min prebreathe with 150 min of continuous ILE. The entire protocol was completed at 14.7 psi. All exercise involved upper body effort. Exercise continued until decompression. V-5) 160 min prebreathe with 140 min of ILE - first 40 min at 14.7 psi, then 30 min at 10.2 psi (breathing 26.5% oxygen) after a 20 min depress, simulating a suit donning period. Subjects were then repressed to 14.7 psi and performed another 50 min of lower body ILE, followed by 50 min rest before decompression. The V-4 protocol was rejected with 3 DCS/6 person-exposures. Initial V-5 testing has produced 0 DCS/11 person-exposures (ongoing trials). The difference in DCS rate was significant (Fisher Exact p=0.029). The observations of DCS were significantly lower in early V-5 trials than in V-4 trials. Additional studies are required to evaluate the relative contribution of the variables in exercise distribution, the 10.2 psi depress/repress component, pre-decompression rest, or possible variation in total oxygen consumption.

Occasional Papers in Open and Distance Learning, Number 14.

ERIC Educational Resources Information Center

Donnan, Peter, Ed.

Five papers focussing on educational technology are presented in this issue. "Computerised Instructional Technologies: Considerations for Lectures and Instructional Designers" (Helen Geissinger) and "The Higher Education Distance Learner and Technology" (Terry Geddes) locates the new technologies within a solidly grounded…

Exercise to improve self-esteem in children and young people.

PubMed

Ekeland, E; Heian, F; Hagen, K B; Abbott, J; Nordheim, L

2004-01-01

Psychological and behavioural problems in children and adolescents are common, and improving self-esteem may help to prevent the development of such problems. There is strong evidence for the positive physical health outcomes of exercise, but the evidence of exercise on mental health is scarce. To determine if exercise alone or exercise as part of a comprehensive intervention can improve self-esteem among children and young people. Computerised searches in MEDLINE, EMBASE, The Cochrane Controlled Trials Register (CENTRAL), CINAHL, PsycINFO and ERIC were undertaken and reference lists from relevant articles were scanned. Relevant studies were also traced by contacting authors. Dates of most recent searches: May 2003 in (CENTRAL), all others: January 2002. Randomised controlled trials where the study population consisted of children and young people aged from 3 to 20 years, in which one intervention arm was gross motor activity for more than four weeks and the outcome measure was self-esteem. Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when necessary. Twenty-three trials with a total of 1821 children and young people were included. Generally, the trials were small, and only one was assessed to have a low risk of bias. Thirteen trials compared exercise alone with no intervention. Eight were included in the meta-analysis, and overall the results were heteregeneous. One study with a low risk of bias showed a standardised mean difference (SMD) of 1.33 (95% CI 0.43 to 2.23), while the SMD's for the three studies with a moderate risk of bias and the four studies with a high risk of bias was 0.21 (95% CI -0.17 to 0.59) and 0.57 (95% CI 0.11 to 1.04), respectively. Twelve trials compared exercise as part of a comprehensive programme with no intervention. Only four provided data sufficient to calculate overall effects, and the results indicate a moderate short-term difference in self-esteem in favour of the intervention [SMD 0.51 (95% CI 0.15 to 0.88)]. The results indicate that exercise has positive short-term effects on self-esteem in children and young people. Since there are no known negative effects of exercise and many positive effects on physical health, exercise may be an important measure in improving children's self-esteem. These conclusions are based on several small low-quality trials.

Interface design recommendations for computerised clinical audit and feedback: Hybrid usability evidence from a research-led system.

PubMed

Brown, Benjamin; Balatsoukas, Panos; Williams, Richard; Sperrin, Matthew; Buchan, Iain

2016-10-01

Audit and Feedback (A&F) is a widely used quality improvement technique that measures clinicians' clinical performance and reports it back to them. Computerised A&F (e-A&F) system interfaces may consist of four key components: (1) Summaries of clinical performance; (2) Patient lists; (3) Patient-level data; (4) Recommended actions. There is a lack of evidence regarding how to best design e-A&F interfaces; establishing such evidence is key to maximising usability, and in turn improving patient safety. To evaluate the usability of a novel theoretically-informed and research-led e-A&F system for primary care (the Performance Improvement plaN GeneratoR: PINGR). (1) Describe PINGR's design, rationale and theoretical basis; (2) Identify usability issues with PINGR; (3) Understand how these issues may interfere with the cognitive goals of end-users; (4) Translate the issues into recommendations for the user-centred design of e-A&F systems. Eight experienced health system evaluators performed a usability inspection using an innovative hybrid approach consisting of five stages: (1) Development of representative user tasks, Goals, and Actions; (2) Combining Heuristic Evaluation and Cognitive Walkthrough methods into a single protocol to identify usability issues; (3) Consolidation of issues; (4) Severity rating of consolidated issues; (5) Analysis of issues according to usability heuristics, interface components, and Goal-Action structure. A final list of 47 issues were categorised into 8 heuristic themes. The most error-prone heuristics were 'Consistency and standards' (13 usability issues; 28% of the total) and 'Match between system and real world' (n=10, 21%). The recommended actions component of the PINGR interface had the most usability issues (n=21, 45%), followed by patient-level data (n=5, 11%), patient lists (n=4, 9%), and summaries of clinical performance (n=4, 9%). The most error-prone Actions across all user Goals were: (1) Patient selection from a list; (2) Data identification from a figure (both population-level and patient-level); (3) Disagreement with a system recommendation. By contextualising our findings within the wider literature on health information system usability, we provide recommendations for the design of e-A&F system interfaces relating to their four key components, in addition to how they may be integrated within a system. Copyright © 2016. Published by Elsevier Ireland Ltd.

SU-E-T-620: Dosimetric Compliance Study for a New Prostate Protocol of Combined High Dose Rate Brachytherapy and Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, C; Giaddui, T; Den, R

2014-06-15

Purpose: To investigate the adherence of treatment plans of prostate cancer patients with the dosimetric compliance criteria of the new in house phase I trial of high dose rate (HDR) brachytherapy combined with stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer patients. Methods: Ten prostate cancer patients were treated using this trial. They received one fraction of HDR to 15Gy, followed by external beam(EB) boost of 3.2Gy(Level 1, five patients) or 3.94Gy(level 2, five patients) per fraction for 10 or 7 fractions, respectively, both equivalent to EB treatments of 113.5Gy in 2Gy fractions. The EB plans were either IMRTmore » or VMAT plans. DVH analysis was performed to verify the adherence of treatment plans to the dosimetric criteria of the trial. Results: For Level 1 patients, target coverage were adequate, with CTV V32Gy(%) of 99.0±1.0 (mean ± 1 standard deviation), and PTV V31Gy(%) of 99.6±0.3. PTV V32.9Gy(%) is 1.4±3.1 and PTVmax is 32.9±0.2Gy. Rectum, bladder and femoral heads sparing were well within protocol criteria. For Level 2 patients, CTV V27.6Gy(%) is 98.7±1.8; PTV V26.7Gy(%) is 99.0±1.4. PTV V28.4Gy(%) is 1.3±1.4, with three patients having minor deviation from protocol. Again critical structures were spared compliant to the protocol. The analysis of HDR plans show similar results, with adequate dose coverage to the prostate and sparing of critical structures including urethra and rectum. V100(%) and V90(%) of prostate are 96.0±1.1 and 98.9±0.5. Urethra D10(%) is 113.1±2.9. Rectum V80(cc) is 1.4±0.5. Hotspot in prostate is substantially higher than what the protocol specifies. But the criteria for hotspot are only guidelines, serving to lower the dose to urethra . Conclusion: This new high biological equivalent dose prostate trial has been carried out successfully for ten patients. Based on dosimetric analysis, all HDR and external plans were compliant to the protocol criteria, with only minor deviations.« less

Visual modifications on the P300 speller BCI paradigm

NASA Astrophysics Data System (ADS)

Salvaris, M.; Sepulveda, F.

2009-08-01

The best known P300 speller brain-computer interface (BCI) paradigm is the Farwell and Donchin paradigm. In this paper, various changes to the visual aspects of this protocol are explored as well as their effects on classification. Changes to the dimensions of the symbols, the distance between the symbols and the colours used were tested. The purpose of the present work was not to achieve the highest possible accuracy results, but to ascertain whether these simple modifications to the visual protocol will provide classification differences between them and what these differences will be. Eight subjects were used, with each subject carrying out a total of six different experiments. In each experiment, the user spelt a total of 39 characters. Two types of classifiers were trained and tested to determine whether the results were classifier dependant. These were a support vector machine (SVM) with a radial basis function (RBF) kernel and Fisher's linear discriminant (FLD). The single-trial classification results and multiple-trial classification results were recorded and compared. Although no visual protocol was the best for all subjects, the best performances, across both classifiers, were obtained with the white background (WB) visual protocol. The worst performance was obtained with the small symbol size (SSS) visual protocol.

Language and Implicit Attributions in the Nuremberg Trials: Analyzing Prosecutors' and Defense Attorneys' Closing Speeches.

ERIC Educational Resources Information Center

Schmid, Jeannette; Fiedler, Klaus

1996-01-01

Investigates attributional implications of prosecutors' and defense attorneys' language strategies using the protocols of the historical Nuremberg trials. States that apart from more positive statements regarding the defendants being made by defense lawyers than prosecutors, both sides used a number of subtler strategies. (PA)

Challenges in the design and implementation of the Multicenter Uveitis Steroid Treatment (MUST) Trial--lessons for comparative effectiveness trials.

PubMed

Holbrook, Janet T; Kempen, John H; Prusakowski, Nancy A; Altaweel, Michael M; Jabs, Douglas A

2011-12-01

Randomized clinical trials (RCTs) are an important component of comparative effectiveness (CE) research because they are the optimal design for head-to-head comparisons of different treatment options. To describe decisions made in the design of the Multicenter Uveitis Steroid Treatment (MUST) Trial to ensure that the results would be widely generalizable. Review of design and implementation decisions and their rationale for the trial. The MUST Trial is a multicenter randomized controlled CE trial evaluating a novel local therapy (intraocular fluocinolone acetonide implant) versus the systemic therapy standard of care for noninfectious uveitis. Decisions made in protocol design in order to broaden enrollment included allowing patients with very poor vision and media opacity to enroll and including clinical sites outside the United States. The treatment protocol was designed to follow standard care. The primary outcome, visual acuity, is important to patients and can be evaluated in all eyes with uveitis. Other outcomes include patient-reported visual function, quality of life, and disease and treatment related complications. The trial population is too small for subgroup analyses that are of interest and the trial is being conducted at tertiary medical centers. CE trials require greater emphasis on generalizability than many RCTs but otherwise face similar challenges for design choices as any RCT. The increase in heterogeneity in patients and treatment required to ensure generalizability can be balanced with a rigorous approach to implementation, outcome assessment, and statistical design. This approach requires significant resources that may limit implementation in many RCTs, especially in clinical practice settings.

Electroacupuncture versus sham electroacupuncture for urinary retention in poststroke patients: study protocol for a multicenter, randomized controlled trial.

PubMed

Shin, Seungwon; Lee, Jiwon; Yoo, Junghee; Lim, Sung Min; Lee, Euiju

2016-04-12

This study protocol evaluates the effectiveness of adjuvant electroacupuncture (EA) for urinary retention in poststroke patients undergoing conventional treatments, in comparison with that of a sham control. A multicenter, blinded, randomized controlled trial will be conducted in three hospitals in the Republic of Korea. We are recruiting 54 stroke survivors (aged >19 years), who were diagnosed with urinary retention based on the results of two consecutive post-void residual (PVR) tests, and dividing them randomly into two arms: the EA and Park-sham control groups. They will receive ten sessions of EA or sham treatment for 2 weeks. The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators. The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention. Then, the Korean version of the Qualiveen Questionnaire, the Korean version of the International Prostate Symptom Score, and the blinding index will be assessed. After each EA session or sham EA, adverse events will be reported to evaluate the safety of EA. Results will be analyzed by using the independent t-test or Mann-Whitney U test, based on both intention-to-treat and per-protocol principles. The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors. This study protocol was registered in ClinicalTrials.gov (NCT02472288) on 10 June 2015.

A Randomized Trial Comparing Two Tongue-Pressure Resistance Training Protocols for Post-Stroke Dysphagia.

PubMed

Steele, Catriona M; Bayley, Mark T; Peladeau-Pigeon, Melanie; Nagy, Ahmed; Namasivayam, Ashwini M; Stokely, Shauna L; Wolkin, Talia

2016-06-01

The objective of this study was to compare the outcomes of two tongue resistance training protocols. One protocol ("tongue-pressure profile training") emphasized the pressure-timing patterns that are typically seen in healthy swallows by focusing on gradual pressure release and saliva swallowing tasks. The second protocol ("tongue-pressure strength and accuracy training") emphasized strength and accuracy in tongue-palate pressure generation and did not include swallowing tasks. A prospective, randomized, parallel allocation trial was conducted. Of 26 participants who were screened for eligibility, 14 received up to 24 sessions of treatment. Outcome measures of posterior tongue strength, oral bolus control, penetration-aspiration and vallecular residue were made based on videofluoroscopy analysis by blinded raters. Complete data were available for 11 participants. Significant improvements were seen in tongue strength and post-swallow vallecular residue with thin liquids, regardless of treatment condition. Stage transition duration (a measure of the duration of the bolus presence in the pharynx prior to swallow initiation, which had been chosen to capture impairments in oral bolus control) showed no significant differences. Similarly, significant improvements were not seen in median scores on the penetration-aspiration scale. This trial suggests that tongue strength can be improved with resistance training for individuals with tongue weakness following stroke. We conclude that improved penetration-aspiration does not necessarily accompany improvements in tongue strength; however, tongue-pressure resistance training does appear to be effective for reducing thin liquid vallecular residue.

Imaging Radiation Doses and Associated Risks and Benefits in Subjects Participating in Breast Cancer Clinical Trials

PubMed Central

Spera, Gonzalo; Meyer, Carlos; Cabral, Pablo; Mackey, John R.

2015-01-01

Background. Medical imaging is commonly required in breast cancer (BC) clinical trials to assess the efficacy and/or safety of study interventions. Despite the lack of definitive epidemiological data linking imaging radiation with cancer development in adults, concerns exist about the risks of imaging radiation-induced malignancies (IRIMs) in subjects exposed to repetitive imaging. We estimated the imaging radiation dose and IRIM risk in subjects participating in BC trials. Materials and Methods. The imaging protocol requirements in 10 phase III trials in the adjuvant and advanced settings were assessed to estimate the effective radiation dose received by a typical and fully compliant subject in each trial. For each study, the excess lifetime attributable cancer risk (LAR) was calculated using the National Cancer Institute’s Radiation Risk Assessment Tool, version 3.7.1. Dose and risk calculations were performed for both imaging intensive and nonintensive approaches to reflect the variability in imaging performed within the studies. Results. The total effective imaging radiation dose was 0.4–262.2 mSv in adjuvant trials and 26–241.3 mSv in metastatic studies. The dose variability resulted from differing protocol requirements and imaging intensity approaches, with computed tomography, multigated acquisition scans, and bone scans as the major contributors. The mean LAR was 1.87–2,410/100,000 in adjuvant trials (IRIM: 0.0002%–2.41% of randomized subjects) and 6.9–67.3/100,000 in metastatic studies (IRIM: 0.007%–0.067% of subjects). Conclusion. IRIMs are infrequent events. In adjuvant trials, aligning the protocol requirements with the clinical guidelines’ surveillance recommendations and substituting radiating procedures with equivalent nonradiating ones would reduce IRIM risk. No significant risk has been observed in metastatic trials, and potential concerns on IRIMs are not justified. Implications for Practice: Medical imaging is key in breast cancer (BC) clinical trials. Most of these procedures expose patients to ionizing radiation, and the risk of second cancer development after imaging has prompted recent concerns and controversy. Using accepted calculation models, the number of malignancies were estimated that were potentially attributable to the imaging procedures performed during a patient’s participation in BC clinical trials. The results show that for patients participating in metastatic trials, the risk of imaging radiation-induced malignancies is negligible. In adjuvant trials, some second cancers due to imaging could be expected, and measures can be taken to reduce their risk. PMID:26025934

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca; Straube, William; Laurie, Fran

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

Effects of training with a passive hand orthosis and games at home in chronic stroke: a pilot randomised controlled trial.

PubMed

Nijenhuis, Sharon M; Prange-Lasonder, Gerdienke B; Stienen, Arno Ha; Rietman, Johan S; Buurke, Jaap H

2017-02-01

To compare user acceptance and arm and hand function changes after technology-supported training at home with conventional exercises in chronic stroke. Secondly, to investigate the relation between training duration and clinical changes. A randomised controlled trial. Training at home, evaluation at research institute. Twenty chronic stroke patients with severely to mildly impaired arm and hand function. Participants were randomly assigned to six weeks (30 minutes per day, six days a week) of self-administered home-based arm and hand training using either a passive dynamic wrist and hand orthosis combined with computerised gaming exercises (experimental group) or prescribed conventional exercises from an exercise book (control group). Main outcome measures are the training duration for user acceptance and the Action Research Arm Test for arm and hand function. Secondary outcomes are the Intrinsic Motivation Inventory, Fugl-Meyer assessment, Motor Activity Log, Stroke Impact Scale and grip strength. The control group reported a higher training duration (189 versus 118 minutes per week, P = 0.025). Perceived motivation was positive and equal between groups ( P = 0.935). No differences in clinical outcomes over training between groups were found (P ⩾ 0.165). Changes in Box and Block Test correlated positively with training duration ( P = 0.001). Both interventions were accepted. An additional benefit of technology-supported arm and hand training over conventional arm and hand exercises at home was not demonstrated. Training duration in itself is a major contributor to arm and hand function improvements.

Real-world research and the role of observational data in the field of gynaecology - a practical review.

PubMed

Heikinheimo, Oskari; Bitzer, Johannes; García Rodríguez, Luis

2017-08-01

In the context of women's health, we examine (1) the role that observational ('real-world') studies have in overcoming limitations of randomised clinical trials, (2) the relative advantages and disadvantages of different study designs, (3) the importance of outcome data from observational studies when making health-economic or clinical decisions, and (4) provide insights into changing perceptions of observational clinical data. PubMed and internet searches were used to identify (i) guidance and expert commentary on designing, conducting, analysing, and reporting clinical trials or observational studies, (ii) supporting evidence of the rapid growth of observational ('real world') studies and publications since the turn of millennium in the fields of contraception, reproductive health, obstetrics or gynaecology. The rapidly growing use and validation of large, computerised medical records and related databases (e.g., health insurance or national registries) have played a major part in changing perceptions of observational data among researchers and clinicians. In the past 10 years, a distinct increase in the number of observational studies published tends to confirm their growing acceptance, appreciation and use. Observational studies can provide information that is impossible or infeasible to obtain otherwise (e.g., impractical, very expensive, or ethically unacceptable). Greater understanding, dissemination, uptake and use of observational data might be expected to drive ongoing evolution of research, data collection, analysis, and validation, in turn improving quality and therefore credibility, utility, and further application by clinicians.

Concurrent aerobic plus resistance exercise versus aerobic exercise alone to improve health outcomes in paediatric obesity: a systematic review and meta-analysis.

PubMed

García-Hermoso, Antonio; Ramírez-Vélez, Robinson; Ramírez-Campillo, Rodrigo; Peterson, Mark D; Martínez-Vizcaíno, Vicente

2018-02-01

To determine if the combination of aerobic and resistance exercise is superior to aerobic exercise alone for the health of obese children and adolescents. Systematic review with meta-analysis. Computerised search of 3 databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry). Studies that compared the effect of supervised concurrent exercise versus aerobic exercise interventions, with anthropometric and metabolic outcomes in paediatric obesity (6-18 years old). The mean differences (MD) of the parameters from preintervention to postintervention between groups were pooled using a random-effects model. 12 trials with 555 youths were included in the meta-analysis. Compared with aerobic exercise alone, concurrent exercise resulted in greater reductions in body mass (MD=-2.28 kg), fat mass (MD=-3.49%; and MD=-4.34 kg) and low-density lipoprotein cholesterol (MD=-10.20 mg/dL); as well as greater increases in lean body mass (MD=2.20 kg) and adiponectin level (MD=2.59 μg/mL). Differences were larger for longer term programmes (>24 weeks). Concurrent aerobic plus resistance exercise improves body composition, metabolic profiles, and inflammatory state in the obese paediatric population. CRD42016039807. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Waste the waist: a pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk.

PubMed

Greaves, Colin; Gillison, Fiona; Stathi, Afroditi; Bennett, Paul; Reddy, Prasuna; Dunbar, James; Perry, Rachel; Messom, Daniel; Chandler, Roger; Francis, Margaret; Davis, Mark; Green, Colin; Evans, Philip; Taylor, Gordon

2015-01-16

In the UK, thousands of people with high cardiovascular risk are being identified by a national risk-assessment programme (NHS Health Checks). Waste the Waist is an evidence-informed, theory-driven (modified Health Action Process Approach), group-based intervention designed to promote healthy eating and physical activity for people with high cardiovascular risk. This pilot randomised controlled trial aimed to assess the feasibility of delivering the Waste the Waist intervention in UK primary care and of conducting a full-scale randomised controlled trial. We also conducted exploratory analyses of changes in weight. Patients aged 40-74 with a Body Mass Index of 28 or more and high cardiovascular risk were identified from risk-assessment data or from practice database searches. Participants were randomised, using an online computerised randomisation algorithm, to receive usual care and standardised information on cardiovascular risk and lifestyle (Controls) or nine sessions of the Waste the Waist programme (Intervention). Group allocation was concealed until the point of randomisation. Thereafter, the statistician, but not participants or data collectors were blinded to group allocation. Weight, physical activity (accelerometry) and cardiovascular risk markers (blood tests) were measured at 0, 4 and 12 months. 108 participants (22% of those approached) were recruited (55 intervention, 53 controls) from 6 practices and 89% provided data at both 4 and 12 months. Participants had a mean age of 65 and 70% were male. Intervention participants attended 72% of group sessions. Based on last observations carried forward, the intervention group did not lose significantly more weight than controls at 12 months, although the difference was significant when co-interventions and co-morbidities that could affect weight were taken into account (Mean Diff 2.6Kg. 95%CI: -4.8 to -0.3, p = 0.025). No significant differences were found in physical activity. The Waste the Waist intervention is deliverable in UK primary care, has acceptable recruitment and retention rates and produces promising preliminary weight loss results. Subject to refinement of the physical activity component, it is now ready for evaluation in a full-scale trial. Current Controlled Trials ISRCTN10707899 .

A multi-centre randomised trial to compare the effectiveness of geriatrician-led admission avoidance hospital at home versus inpatient admission.

PubMed

Shepperd, Sasha; Cradduck-Bamford, Andrea; Butler, Chris; Ellis, Graham; Godfrey, Mary; Gray, Alastair; Hemsley, Anthony; Khanna, Pradeep; Langhorne, Peter; McCaffrey, Patricia; Mirza, Lubena; Pushpangadan, Maj; Ramsay, Scott; Schiff, Rebekah; Stott, David; Young, John; Yu, Ly-Mee

2017-10-23

There is concern that existing models of acute hospital care will become unworkable as the health service admits an increasing number of frail older people with complex health needs, and that there is inadequate evidence to guide the planning of acute hospital level services. We aim to evaluate whether geriatrician-led admission avoidance to hospital at home is an effective alternative to hospital admission. We are conducting a multi-site randomised open trial of geriatrician-led admission avoidance hospital at home, compared with admission to hospital. We are recruiting older people with markers of frailty or prior dependence who have been referred to admission avoidance hospital at home for an acute medical event. This includes patients presenting with delirium, functional decline, dependence, falls, immobility or a background of dementia presenting with physical disease. Participants are randomised using a computerised random number generator to geriatrician-led admission avoidance hospital at home or a control group of inpatient admission in a 2:1 ratio in favour of the intervention. The primary endpoint 'living at home' (the inverse of death or living in a residential care setting) is measured at 6 months follow-up, and we also collect data on this outcome at 12 months. Secondary outcomes include the incidence of delirium, mortality, new long-term residential care, cognitive impairment, activities of daily living, quality of life and quality-adjusted survival, length of stay, readmission or transfer to hospital. We will conduct a parallel economic evaluation, and a process evaluation that includes an interview study to explore the experiences of patients and carers. Health systems around the world are examining how to provide acute hospital-level care to older adults in greater numbers with a fixed or shrinking hospital resource. This trial is the first large multi-site randomised trial of geriatrician-led admission avoidance hospital at home, and will provide evidence on alternative models of healthcare for older people who require hospital admission. ISRCTN60477865 : Registered on 10 March 2014. Trial Sponsor: University of Oxford. Version 3.1, 14/06/2016.

A Feasibility Randomised Controlled Trial of the New Orleans Intervention for Infant Mental Health: A Study Protocol

PubMed Central

Fitzpatrick, Bridie; Watson, Nicholas; Cotmore, Richard; Wilson, Philip; Donaldson, Julia; Boyd, Kathleen; Zeanah, Charles; Norrie, John; Messow, Martina; Turner, Fiona; Irving, Susan

2013-01-01

Child maltreatment is associated with life-long social, physical, and mental health problems. Intervening early to provide maltreated children with safe, nurturing care can improve outcomes. The need for prompt decisions about permanent placement (i.e., regarding adoption or return home) is internationally recognised. However, a recent Glasgow audit showed that many maltreated children “revolve” between birth families and foster carers. This paper describes the protocol of the first exploratory randomised controlled trial of a mental health intervention aimed at improving placement permanency decisions for maltreated children. This trial compares an infant's mental health intervention with the new enhanced service as usual for maltreated children entering care in Glasgow. As both are new services, the trial is being conducted from a position of equipoise. The outcome assessment covers various fields of a child's neurodevelopment to identify problems in any ESSENCE domain. The feasibility, reliability, and developmental appropriateness of all outcome measures are examined. Additionally, the potential for linkage with routinely collected data on health and social care and, in the future, education is explored. The results will inform a definitive randomised controlled trial that could potentially lead to long lasting benefits for the Scottish population and which may be applicable to other areas of the world. This trial is registered with ClinicalTrials.gov (NC01485510). PMID:24023537

Evaluation of mindfulness-based cognitive therapy for life and a cognitive behavioural therapy stress-management workshop to improve healthcare staff stress: study protocol for two randomised controlled trials.

PubMed

Strauss, Clara; Gu, Jenny; Pitman, Nikki; Chapman, Cavita; Kuyken, Willem; Whittington, Adrian

2018-04-02

Healthcare workers experience higher levels of work-related stress and higher rates of sickness absence than workers in other sectors. Psychological approaches have potential in providing healthcare workers with the knowledge and skills to recognise stress and to manage stress effectively. The strongest evidence for effectiveness in reducing stress in the workplace is for stress-management courses based on cognitive behavioural therapy (CBT) principles and mindfulness-based interventions (MBIs). However, research examining effects of these interventions on sickness absence (an objective indicator of stress) and compassion for others (an indicator of patient care) is limited, as is research on brief CBT stress-management courses (which may be more widely accessible) and on MBIs adapted for workplace settings. This protocol is for two randomised controlled trials with participant preference between the two trials and 1:1 allocation to intervention or wait-list within the preferred choice. The first trial is examining a one-day CBT stress-management workshop and the second trial an 8-session Mindfulness-Based Cognitive Therapy for Life (MBCT-L) course, with both trials comparing intervention to wait-list. The primary outcome for both trials is stress post-intervention with secondary outcomes being sickness absence, compassion for others, depression symptoms, anxiety symptoms, wellbeing, work-related burnout, self-compassion, presenteeism, and mindfulness (MBCT-L only). Both trials aim to recruit 234 staff working in the National Health Service in the UK. This trial will examine whether a one-day CBT stress-management workshop and an 8-session MBCT-L course are effective at reducing healthcare staff stress and other mental health outcomes compared to wait-list, and, whether these interventions are effective at reducing sickness absence and presenteeism and at enhancing wellbeing, self-compassion, mindfulness and compassion for others. Findings will help inform approaches offered to reduce healthcare staff stress and other key variables. A note of caution is that individual-level approaches should only be part of the solution to reducing healthcare staff stress within a broader focus on organisational-level interventions and support. ISRCTN Registry, ISRCTN11723441 . Registered on 16 June 2017. Protocol Version 1: 24 April 2017. Trial Sponsor: Sussex Partnership NHS Foundation Trust (ResearchGovernance@sussexpartnership.nhs.uk).

Computerised Screening for Dyslexia in Adults

ERIC Educational Resources Information Center

Singleton, Chris; Horne, Joanna; Simmons, Fiona

2009-01-01

Identifying dyslexia in adulthood presents particular challenges because of complicating factors such as acquisition of compensatory strategies, differing degrees of intervention and the problem of distinguishing dyslexic adults from those whose literacy difficulties have non-cognitive causes. One of the implications is that conventional literacy…

SU-G-206-01: A Fully Automated CT Tool to Facilitate Phantom Image QA for Quantitative Imaging in Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahi-Anwar, M; Lo, P; Kim, H

Purpose: The use of Quantitative Imaging (QI) methods in Clinical Trials requires both verification of adherence to a specified protocol and an assessment of scanner performance under that protocol, which are currently accomplished manually. This work introduces automated phantom identification and image QA measure extraction towards a fully-automated CT phantom QA system to perform these functions and facilitate the use of Quantitative Imaging methods in clinical trials. Methods: This study used a retrospective cohort of CT phantom scans from existing clinical trial protocols - totaling 84 phantoms, across 3 phantom types using various scanners and protocols. The QA system identifiesmore » the input phantom scan through an ensemble of threshold-based classifiers. Each classifier - corresponding to a phantom type - contains a template slice, which is compared to the input scan on a slice-by-slice basis, resulting in slice-wise similarity metric values for each slice compared. Pre-trained thresholds (established from a training set of phantom images matching the template type) are used to filter the similarity distribution, and the slice with the most optimal local mean similarity, with local neighboring slices meeting the threshold requirement, is chosen as the classifier’s matched slice (if it existed). The classifier with the matched slice possessing the most optimal local mean similarity is then chosen as the ensemble’s best matching slice. If the best matching slice exists, image QA algorithm and ROIs corresponding to the matching classifier extracted the image QA measures. Results: Automated phantom identification performed with 84.5% accuracy and 88.8% sensitivity on 84 phantoms. Automated image quality measurements (following standard protocol) on identified water phantoms (n=35) matched user QA decisions with 100% accuracy. Conclusion: We provide a fullyautomated CT phantom QA system consistent with manual QA performance. Further work will include parallel component to automatically verify image acquisition parameters and automated adherence to specifications. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics; NIH Grant support from: U01 CA181156.« less

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. Methods/Design A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. Discussion The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index – normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed. PMID:24716713

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Gomes, Cid André Fidelis de Paula; Leal-Junior, Ernesto Cesar Pinto; Biasotto-Gonzalez, Daniela Aparecida; El-Hage, Yasmin; Politti, Fabiano; Gonzalez, Tabajara de Oliveira; Dibai-Filho, Almir Vieira; de Oliveira, Adriano Rodrigues; Frigero, Marcelo; Antonialli, Fernanda Colella; Vanin, Adriane Aver; de Tarso Camillo de Carvalho, Paulo

2014-04-09

Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index - normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed.

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

PubMed

Viecelli, Andrea K; Pascoe, Elaine; Polkinghorne, Kevan R; Hawley, Carmel; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Heritier, Stephane; Kerr, Peter G; Mori, Trevor A; Robertson, Amanda; Seong, Hooi L; Irish, Ashley B

2015-06-27

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety. ClinicalTrials.gov, ID: NCT02885948 . Registered retrospectively on 4 July 2016. Protocol Version 2.0, 3 April 2017. Protocol identification (code or reference number): UCDCRC/15/006 EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effectiveness of De Qi during acupuncture for the treatment of tinnitus: study protocol for a randomized controlled trial.

PubMed

Xie, Hui; Li, Xinrong; Lai, Jiaqin; Zhou, Yanan; Wang, Caiying; Liang, Jiao

2014-10-15

Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

PubMed Central

2011-01-01

Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer. Trial registration German Clinical Trial Register Number: DRKS00000040 PMID:21303515

Quantifying and visualizing site performance in clinical trials.

PubMed

Yang, Eric; O'Donovan, Christopher; Phillips, JodiLyn; Atkinson, Leone; Ghosh, Krishnendu; Agrafiotis, Dimitris K

2018-03-01

One of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol. Intuitively, the historical track record of a site is one of the strongest predictors of its future performance; however, issues such as data availability and wide differences in protocol complexity can complicate interpretation. Here, we demonstrate how operational data derived from central laboratory services can provide key insights into the performance of clinical sites and help guide operational planning and site selection for new clinical trials. Our methodology uses the metadata associated with laboratory kit shipments to clinical sites (such as trial and anonymized patient identifiers, investigator names and addresses, sample collection and shipment dates, etc.) to reconstruct the complete schedule of patient visits and derive insights about the operational performance of those sites, including screening, enrollment, and drop-out rates and other quality indicators. This information can be displayed in its raw form or normalized to enable direct comparison of site performance across studies of varied design and complexity. Leveraging Covance's market leadership in central laboratory services, we have assembled a database of operational metrics that spans more than 14,000 protocols, 1400 indications, 230,000 unique investigators, and 23 million patient visits and represents a significant fraction of all clinical trials run globally in the last few years. By analyzing this historical data, we are able to assess and compare the performance of clinical investigators across a wide range of therapeutic areas and study designs. This information can be aggregated across trials and geographies to gain further insights into country and regional trends, sometimes with surprising results. The use of operational data from Covance Central Laboratories provides a unique perspective into the performance of clinical sites with respect to many important metrics such as patient enrollment and retention. These metrics can, in turn, be used to guide operational planning and site selection for new clinical trials, thereby accelerating recruitment, improving quality, and reducing cost.

Real-time intraoperative monitoring of brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm.

PubMed

Joo, Byung-Euk; Park, Sang-Ku; Cho, Kyung-Rae; Kong, Doo-Sik; Seo, Dae-Won; Park, Kwan

2016-11-01

OBJECTIVE The aim of this study was to define a new protocol for intraoperative monitoring (IOM) of brainstem auditory evoked potentials (BAEPs) during microvascular decompression (MVD) surgery to treat hemifacial spasm (HFS) and to evaluate the usefulness of this new protocol to prevent hearing impairment. METHODS To define the optimal stimulation rate, estimate the number of trials to be averaged, and identify useful warning criteria in IOM of BAEPs, the authors performed a preliminary study of 13 patients with HFS in 2010. They increased the stimulation rate from 10.1 Hz/sec to 100.1 Hz/sec by 10-Hz increments, and they elevated the average time from 100 times to 1000 times by 100-unit increments at a fixed stimulus rate of 43.9 Hz. After defining the optimal stimulation rate and the number of trials that needed to be averaged for IOM of BAEPs, they also identified the useful warning criteria for this protocol for MVD surgery. From January to December 2013, 254 patients with HFS underwent MVD surgery following the new IOM of BAEPs protocol. Pure-tone audiometry and speech discrimination scoring were performed before surgery and 1 week after surgery. To evaluate the usefulness of the new protocol, the authors compared the incidence of postoperative hearing impairment with the results from the group that underwent MVD surgery prior to the new protocol. RESULTS Through a preliminary study, the authors confirmed that it was possible to obtain a reliable wave when using a stimulation rate of 43.9 Hz/sec and averaging 400 trials. Only a Wave V amplitude loss > 50% was useful as a warning criterion when using the new protocol. A reliable BAEP could be obtained in approximately 9.1 seconds. When the new protocol was used, 2 patients (0.8%) showed no recovery of Wave V amplitude loss > 50%, and only 1 of those 2 patients (0.39%) ultimately had postoperative hearing impairment. When compared with the outcomes in the pre-protocol group, hearing impairment incidence decreased significantly among patients who underwent surgery with the new protocol (0.39% vs 4.02%, p = 0.002). There were no significant differences between the 2 surgery groups regarding other complications, including facial palsy, sixth cranial nerve palsy, and vocal cord palsy. CONCLUSIONS There was a significant decrease in postoperative hearing impairment after MVD for HFS when the new protocol for IOM of BAEPs was used. Real-time IOM of BAEPs, which can obtain a reliable BAEP in less than 10 seconds, is a successful new procedure for preventing hearing impairment during MVD surgery for HFS.

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Metadata registry and management system based on ISO 11179 for cancer clinical trials information system

PubMed Central

Park, Yu Rang; Kim*, Ju Han

2006-01-01

Standardized management of data elements (DEs) for Case Report Form (CRF) is crucial in Clinical Trials Information System (CTIS). Traditional CTISs utilize organization-specific definitions and storage methods for Des and CRFs. We developed metadata-based DE management system for clinical trials, Clinical and Histopathological Metadata Registry (CHMR), using international standard for metadata registry (ISO 11179) for the management of cancer clinical trials information. CHMR was evaluated in cancer clinical trials with 1625 DEs extracted from the College of American Pathologists Cancer Protocols for 20 major cancers. PMID:17238675

Worldwide trends in volume and quality of published protocols of randomized controlled trials

PubMed Central

Alldinger, Ingo; Cieslak, Kasia P.; Wennink, Roos; Clarke, Mike; Ali, Usama Ahmed; Besselink, Marc G. H.

2017-01-01

Introduction Publishing protocols of randomized controlled trials (RCT) facilitates a more detailed description of study rational, design, and related ethical and safety issues, which should promote transparency. Little is known about how the practice of publishing protocols developed over time. Therefore, this study describes the worldwide trends in volume and methodological quality of published RCT protocols. Methods A systematic search was performed in PubMed and EMBASE, identifying RCT protocols published over a decade from 1 September 2001. Data were extracted on quality characteristics of RCT protocols. The primary outcome, methodological quality, was assessed by individual methodological characteristics (adequate generation of allocation, concealment of allocation and intention-to-treat analysis). A comparison was made by publication period (First, September 2001- December 2004; Second, January 2005-May 2008; Third, June 2008-September 2011), geographical region and medical specialty. Results The number of published RCT protocols increased from 69 in the first, to 390 in the third period (p<0.0001). Internal medicine and paediatrics were the most common specialty topics. Whereas most published RCT protocols in the first period originated from North America (n = 30, 44%), in the second and third period this was Europe (respectively, n = 65, 47% and n = 190, 48%, p = 0.02). Quality of RCT protocols was higher in Europe and Australasia, compared to North America (OR = 0.63, CI = 0.40–0.99, p = 0.04). Adequate generation of allocation improved with time (44%, 58%, 67%, p = 0.001), as did concealment of allocation (38%, 53%, 55%, p = 0.03). Surgical protocols had the highest quality among the three specialty topics used in this study (OR = 1.94, CI = 1.09–3.45, p = 0.02). Conclusion Publishing RCT protocols has become popular, with a five-fold increase in the past decade. The quality of published RCT protocols also improved, although variation between geographical regions and across medical specialties was seen. This emphasizes the importance of international standards of comprehensive training in RCT methodology. PMID:28296925

Dose versus diagnosis: iatrogenic radiation exposure by multidetector computerised tomography in an academic emergency department with measurement of clinically actionable results and emergently treatable findings.

PubMed

Baskerville, J R; Chang, J H; Viator, M; Rutledge, W; Miryala, R; Duval, K E; Nishino, T K

2009-01-01

To determine the iatrogenic absorbed dosage of radiation of the patient in milligray (mGy) computerised tomography dose index volume (CTDIvol) when tested with multidetector computerised tomography (MDCT) in the emergency department (ED) setting and calculate the absorbed dosage of radiation per clinically actionable result and emergently treatable finding (ETF). The University of Texas Medical Branch (UTMB) ED located in Galveston, Texas, USA, is a level 1 trauma and tertiary referral centre treating 70,000 patients per annum. A retrospective cross-sectional data analysis of 770 emergency patients investigated by MDCT in July 2007. The presence of actionable results and ETF were determined by chart review. A total of 5320 emergency patients was treated in the UTMB ED in July 2007. This included 4508 medical and 812 trauma patients. A total of 1094 MDCT studies was performed, of which complete data were available on 1046. A total of 770 patients was investigated by MDCT, representing 14.47% of all emergency patients. This included 33.99% of trauma patients and 10.96% of medical patients. Actionable results were found in 341 studies and ETF in 105 studies. The mean radiation was 163.27 and 530.23 mGy CTDIvol for actionable results and ETF, respectively, for all studies. The mean radiation was 53.27 and 106.36 mGy CTDIvol for medical and trauma patients, respectively. The absorbed dosage of radiation of patients investigated by MDCT is clinically significant. The actionable results and ETF in our study demonstrate considerable opportunity for improvement in the utilisation of this technology by physicians.

Correlation between computerised findings and Newman's scaling on vascularity using power Doppler ultrasonography imaging and its predictive value in patients with plantar fasciitis

PubMed Central

Chen, H; Ho, H M; Ying, M; Fu, S N

2012-01-01

Objectives The purpose of this study was to correlate findings on small vessel vascularity between computerised findings and Newman's scaling using power Doppler ultrasonography (PDU) imaging and its predictive value in patients with plantar fasciitis. Methods PDU was performed on 44 patients (age range 30–66 years; mean age 48 years) with plantar fasciitis and 46 healthy subjects (age range 18–61 years; mean age 36 years). The vascularity was quantified using ultrasound images by a customised software program and graded by Newman's grading scale. Vascular index (VI) was calculated from the software program as the ratio of the number of colour pixels to the total number of pixels within a standardised selected area of proximal plantar fascia. The 46 healthy subjects were examined on 2 occasions 7–10 days apart, and 18 of them were assessed by 2 examiners. Statistical analyses were performed using intraclass correlation coefficient and linear regression analysis. Results Good correlation was found between the averaged VI ratios and Newman's qualitative scale (ρ = 0.70; p<0.001). Intratester and intertester reliability were 0.89 and 0.61, respectively. Furthermore, higher VI was correlated with less reduction in pain after physiotherapeutic intervention. Conclusions The computerised VI not only has a high level of concordance with the Newman grading scale but is also reliable in reflecting the vascularity of proximal plantar fascia, and can predict pain reduction after intervention. This index can be used to characterise the changes in vascularity of patients with plantar fasciitis, and it may also be helpful for evaluating treatment and monitoring the progress after intervention in future studies. PMID:22167513