Systematic review of blinding assessment in randomized controlled trials in schizophrenia and affective disorders 2000-2010.

PubMed

Baethge, Christopher; Assall, Oliver P; Baldessarini, Ross J

2013-01-01

Blinding is an integral part of many randomized controlled trials (RCTs). However, both blinding and blinding assessment seem to be rarely documented in trial reports. Systematic review of articles on RCTs in schizophrenia and affective disorders research during 2000-2010. Among 2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported assessing participant, rater, or clinician blinding: 5/672 reports on schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective disorders, without significant trends across the decade. Rarely was blinding assessed at the beginning, in most studies assessment was at the end. Proportion of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per study, with slightly more correct guesses in treatment arms than in placebo arms. Three fourths of responders correctly guessed that they received the active agent. Blinding assessment was more frequently reported in papers on psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs. 8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was associated with: (a) positive findings, (b) full industrial sponsorship, and (c) diagnosis of schizophrenia. There was a moderate association of treatment success and blinding status of both trial participants (r = 0.51, p = 0.002) and raters (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding documentation of persons blinded (60%) or of efforts to match interventions (50%). Recent treatment trials in major psychiatric disorders rarely reported on or evaluated blinding. We recommend routine documentation of blinding strategies in reports. Copyright © 2013 S. Karger AG, Basel.

Oral vaccine (OM-89) in the recurrent urinary tract infection prophylaxis: a realistic systematic review with meta-analysis.

PubMed

Taha Neto, K A; Nogueira Castilho, L; Reis, L O

2016-05-01

To evaluate the efficacy of Escherichia Coli extract (OM-89) in the prophylaxis of recurrent uncomplicated urinary tract infection (UTI) through a contemporary systematic review and meta-analysis. Inclusion criteria were double-blind randomized trials using orally administrated OM-89, 6mg daily, during three months with a minimum of three months of monitoring. Outcomes were the frequency of bacteriuria in 3 and 6 months, dysuria in 6 months and UTI in 6 months. PubMed, MEDLINE, Cochrane Collaboration and their key references. After analysis by three independent reviewers, 15 double-blind randomized trials were identified, 10 papers excluded due to methods flaws and 5 used for data analysis due to double blinding and reporting drop-outs. Among 5 selected studies the date of publication ranged from 1985 to 2005, totalizing 396 patients in the OM-89 group and 392 in the control group. Overall, there were 61 dropouts in the control group and 76 in the OM-89 group. As a major limitation there was no appropriate description of their methodologies and none of the studies described conflict of interest or commitment to the pharmaceutical industry. All studies were multi-centric, except for two, which showed no clarity on allocation concealment. All studies show benefit in favor of vaccine. Current literature on prospective randomized controlled trials evaluating the use of oral OM-89 vaccine in the recurrent UTI prophylaxis is of low quality, limited to the first six months only and with variable definition of bacteriuria and UTI. Although all studies show benefit in favor of vaccine, no robust trial was identified, resulting in a high heterogeneity in the data analyzed. Also, publication bias could not be excluded and future higher quality studies are warranted adding intermediate (>12 months) and long-term follow-up. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

The DiaS trial: dialectical behavior therapy versus collaborative assessment and management of suicidality on self-harm in patients with a recent suicide attempt and borderline personality disorder traits - study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background In Denmark 8,000 to 10,000 people will attempt suicide each year. The Centre of Excellence in Suicide Prevention in the Capital Region of Denmark is treating patients with suicidal behavior, and a recent survey has shown that 30% of the patients are suffering from borderline personality disorder. The majority of patients (70% to 75%) with borderline personality disorder have a history of deliberate self-harm and 10% have a lifetime risk to die by suicide. The DiaS trial is comparing dialectical behavior therapy with collaborative assessment and management of suicidality-informed supportive psychotherapy, for the risk of repetition of deliberate self-harm in patients with a recent suicide attempt and personality traits within the spectrum of borderline personality disorder. Both treatments have previously shown effects in this group of patients on suicide ideation and self-harm compared with treatment as usual. Methods/Design The trial is designed as a single-center, two-armed, parallel-group observer-blinded randomized clinical superiority trial. We will recruit 160 participants with a recent suicide attempt and at least two traits of the borderline personality disorder from the Centre of Excellence in Suicide Prevention, Capital Region of Denmark. Randomization will be performed though a centralized and computer-generated approach that conceals the randomization sequence. The interventions that are offered are a modified version of a dialectical behavior therapy program lasting 16 weeks versus collaborative assessment and management of suicidality-informed supportive psychotherapy, where the duration treatment will vary in accordance with established methods up to 16 weeks. The primary outcome measure is the ratio of deliberate self-harming acts including suicide attempts measured at week 28. Other exploratory outcomes are included such as severity of symptoms, suicide intention and ideation, depression, hopelessness, self-esteem, impulsivity, anger, and duration of respective treatments. Trial registration Clinical Trial.gov: NCT01512602. PMID:24885904

Interagency Collaboration for Young Adults with Deaf-Blindness: Toward a Common Transition Goal.

ERIC Educational Resources Information Center

Everson, Jane M.; And Others

This monograph is a compilation of the knowledge gained by the Technical Assistance Center (TAC) of the Helen Keller National Center, from training and technical assistance activities conducted with state interagency teams serving youth and young adults with deaf-blindness. The book views interagency collaboration as essential in achieving…

The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

PubMed

Vaccarino, Anthony L; Evans, Kenneth R; Kalali, Amir H; Kennedy, Sidney H; Engelhardt, Nina; Frey, Benicio N; Greist, John H; Kobak, Kenneth A; Lam, Raymond W; MacQueen, Glenda; Milev, Roumen; Placenza, Franca M; Ravindran, Arun V; Sheehan, David V; Sills, Terrence; Williams, Janet B W

2016-01-01

The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.

Investigating the effect of independent, blinded digital image assessment on the STOP GAP trial.

PubMed

Patsko, Emily; Godolphin, Peter J; Thomas, Kim S; Hepburn, Trish; Mitchell, Eleanor J; Craig, Fiona E; Bath, Philip M; Montgomery, Alan A

2017-02-02

Blinding is the process of keeping treatment assignment hidden and is used to minimise the possibility of bias. Trials at high risk of bias have been shown to report larger treatment effects than low-risk studies. In dermatology, one popular method of blinding is to have independent outcome assessors who are unaware of treatment allocation assessing the endpoint using digital photographs. However, this can be complex, expensive and time-consuming. The objective of this study was to compare the effect of blinded and unblinded outcome assessment on the results of the STOP GAP trial. The STOP GAP trial compared prednisolone to ciclosporin in treating pyoderma gangrenosum. Participants' lesions were measured at baseline and at 6 weeks to calculate the primary outcome, speed of healing. Independent blinded assessors obtained measurements from digital photographs using specialist software. In addition, unblinded treating clinicians estimated lesion area by measuring length and width. The primary outcome was determined using blinded measurements where available, otherwise unblinded measurements were used (method referred to as trial measurements). In this study, agreement between the trial and unblinded measurements was determined using the intraclass correlation coefficient (ICC). The STOP GAP trial's primary analysis was repeated using unblinded measurements only. We introduced differential and nondifferential error in unblinded measurements and investigated the effect on the STOP GAP trial's primary analysis. Eighty-six (80%) of the 108 patients were assessed using digital images. Agreement between trial and unblinded measurements was excellent (ICC = 0.92 at baseline; 0.83 at 6 weeks). There was no evidence that the results of the trial primary analysis differed according to how the primary outcome was assessed (p value for homogeneity = 1.00). Blinded digital image assessment in the STOP GAP trial did not meaningfully alter trial conclusions compared with unblinded assessment. However, as the process brought added accuracy and credibility to the trial it was considered worthwhile. These findings question the usefulness of digital image assessment in a trial with an objective outcome and where bias is not expected to be excessive. Further research should investigate if there are alternative, less complex ways of incorporating blinding in clinical trials. Current Controlled Trials, www.isrctn.com ISRCTN35898459. Registered on 26 May 2009.

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups?

PubMed Central

2014-01-01

Background Studies suggest that expectations powerfully shape clinical outcomes. For subjective outcomes in adequately blinded trials, health improvements are substantial and largely explained by non-specific factors. The objective of this study was to investigate if unblinding in randomized controlled trials (RCTs) is associated with enhanced placebo effects for intervention groups and nocebo effects for placebo groups. For these effects, a secondary objective was to explore potential moderating factors. Methods We included RCTs that investigated the efficacy of phosphodiesterase-5 (PDE-5) inhibitors for male erectile dysfunction by comparing one PDE-5 inhibitor to placebo. In addition, to be included studies must have reported scores for change from baseline, or baseline and final International Index of Erectile Functioning-Erectile Functioning domain score (IIEF-EF), and be published in either English, French, Dutch, or German. We searched for both published and unpublished relevant trials using PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials, a clinical trials register (clinicaltrials.gov) and the Food and Drug Administration clinical reviews through March 2012. We evaluated the blinding status of trials with the Cochrane Risk of Bias Tool, using the domains of allocation sequence concealment, blinding of participants, healthcare providers and outcome assessors. Across these four domains, studies that scored low risk of bias were judged to be adequately blinded and studies that scored unclear or high risk of bias were judged to be inadequately blinded. Results We included 110 studies (205 journal publications and 2 unpublished sources) that involved 23,877 participants; 93 (85%), 51 (46%), 93 (85%) and 93 (85%) studies were assessed with an unclear risk of bias for allocation concealment, blinding of participant, blinding of caregiver and blinding of outcome assessor, respectively. None of the studies reported testing of blinding. None of the 205 journal publications provided sufficient details to assess allocation concealment, blinding of participants, caregivers and outcome assessors. After contacting authors for additional information, we judged five studies to be adequately (n = 1,202) and 16 to be inadequately (n = 3,006) blinded. The IIEF-EF score for placebo groups in adequately blinded trials versus inadequately blinded trials was 1.92 points (95% CI, 0.64 to 3.20) versus 1.56 (95% CI, 0.93 to 2.20), respectively. The IIEF-EF score for intervention groups in adequately blinded trials versus inadequately blinded trials was 9.40 (95% CI, 6.96 to 11.83) versus 8.33 (95% CI, 7.29 to 9.37), respectively. In a secondary analysis, prior experience with the drug affected the scores; in placebo groups with participants naïve to the intervention the score was 2.89 (95% CI, 2.33 to 3.45) versus -0.11 (95% CI, -2.06 to 1.84) with participants having prior experience. In the intervention groups, these scores were 7.99 (95% CI, 6.85 to 9.14) versus 8.33 (95% CI, 7.51 to 9.16), respectively. Unblinding lowered placebo scores (creating a nocebo effect) by 19% (0.33 points; 95% CI, -0.96 to 1.62). Unblinding lowered intervention scores by 11% (1.0; 95% CI, -1.35 to 3.47). The results provided no conclusive evidence for nocebo or enhanced placebo effects. Patients taking a PDE-5 inhibitor for the first time experience a larger placebo effect that accounts for 35% of the total effect. Conclusions Given the overall poor reporting of blinding in clinical trial reports and the small number of trials that could be rated as adequately or inadequately blinded, we could not draw any robust conclusions about the existence or absence of nocebo and enhanced placebo effects. A large placebo effect was found for patients taking PDE-5 inhibitors for the first time. It was not clear if previous exposure to the drug impacted trial blinding. We found clear evidence that studies assessing a subjective continuous outcome fail to report on measures taken to secure double blinding. Although we observed a trend for the presence of a nocebo effect, there was insufficient evidence to quantify its impact on expectations. RCTs with patients with no prior experience with PDE-5 inhibitors reported larger placebo effects and possibly these studies were better blinded. Future research should further investigate the factors that contribute to blinding and their impact on health outcomes in randomized trials of subjectively assessed conditions. This research is part of a PhD project and has no external funding. The authors have no competing interests to declare. PMID:24555576

Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening.

PubMed

Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander; Fourkala, Evangelia-Ourania; Dawnay, Anne; Burnell, Matthew; Zaikin, Alexey; Burchell, Joy; Papadimitriou, Joyce Taylor; Clausen, Henrik; Jacobs, Ian; Menon, Usha; Wandall, Hans H

2014-05-01

Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels before clinical diagnosis, and their utility in cancer screening in the general population. In our study, we have generated O-glycosylated synthetic MUC1 and MUC4 peptides in vitro, to mimic cancer-associated glycoforms, and displayed these on microarrays. The assay's performance was tested through an initial screening of serum samples taken from patients at the time of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after recruitment and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2 and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity to 32.0% at 95% specificity. These findings suggest that a combination of antibody signatures may have a role as part of a biomarker panel for the early detection of colorectal cancer.

20 CFR 404.1585 - Trial work period for persons age 55 or older who are blind.

Code of Federal Regulations, 2011 CFR

2011-04-01

... who are blind. 404.1585 Section 404.1585 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL... § 404.1585 Trial work period for persons age 55 or older who are blind. If you become eligible for disability benefits even though you were doing substantial gainful activity because you are blind and age 55...

20 CFR 404.1585 - Trial work period for persons age 55 or older who are blind.

Code of Federal Regulations, 2012 CFR

2012-04-01

... who are blind. 404.1585 Section 404.1585 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL... § 404.1585 Trial work period for persons age 55 or older who are blind. If you become eligible for disability benefits even though you were doing substantial gainful activity because you are blind and age 55...

20 CFR 404.1585 - Trial work period for persons age 55 or older who are blind.

Code of Federal Regulations, 2014 CFR

2014-04-01

... who are blind. 404.1585 Section 404.1585 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL... § 404.1585 Trial work period for persons age 55 or older who are blind. If you become eligible for disability benefits even though you were doing substantial gainful activity because you are blind and age 55...

20 CFR 404.1585 - Trial work period for persons age 55 or older who are blind.

Code of Federal Regulations, 2013 CFR

2013-04-01

... who are blind. 404.1585 Section 404.1585 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL... § 404.1585 Trial work period for persons age 55 or older who are blind. If you become eligible for disability benefits even though you were doing substantial gainful activity because you are blind and age 55...

Memory impairment is not sufficient for choice blindness to occur.

PubMed

Sagana, Anna; Sauerland, Melanie; Merckelbach, Harald

2014-01-01

Choice blindness refers to the phenomenon that people can be easily misled about the choices they made in the recent past. The aim of this study was to explore the cognitive mechanisms underlying choice blindness. Specifically, we tested whether memory impairment may account for choice blindness. A total of N = 88 participants provided sympathy ratings on 10-point scales for 20 female faces. Subsequently, participants motivated some of their ratings. However, on three trials, they were presented with sympathy ratings that deviated from their original ratings by three full scale points. On nearly 41% of the trials, participants failed to detect (i.e., were blind) the manipulation. After a short interval, participants were informed that some trials had been manipulated and were asked to recall their original ratings. Participants adopted the manipulated outcome in only 3% of the trials. Furthermore, the extent to which the original ratings were accurately remembered was not higher for detected as compared with non-detected trials. From a theoretical point of view our findings indicate that memory impairment does not fully account for blindness phenomena.

Memory impairment is not sufficient for choice blindness to occur

PubMed Central

Sagana, Anna; Sauerland, Melanie; Merckelbach, Harald

2014-01-01

Choice blindness refers to the phenomenon that people can be easily misled about the choices they made in the recent past. The aim of this study was to explore the cognitive mechanisms underlying choice blindness. Specifically, we tested whether memory impairment may account for choice blindness. A total of N = 88 participants provided sympathy ratings on 10-point scales for 20 female faces. Subsequently, participants motivated some of their ratings. However, on three trials, they were presented with sympathy ratings that deviated from their original ratings by three full scale points. On nearly 41% of the trials, participants failed to detect (i.e., were blind) the manipulation. After a short interval, participants were informed that some trials had been manipulated and were asked to recall their original ratings. Participants adopted the manipulated outcome in only 3% of the trials. Furthermore, the extent to which the original ratings were accurately remembered was not higher for detected as compared with non-detected trials. From a theoretical point of view our findings indicate that memory impairment does not fully account for blindness phenomena. PMID:24904467

Short-term and long-term collaboration benefits on individual recall in younger and older adults

PubMed Central

Stern, Yaakov

2011-01-01

A recent study of younger adults suggests that, compared to repeated individual recall trials, repeated collaborative recall trials produce better individual recall after a short delay (Blumen & Rajaram, 2008). Our study was designed to determine if such collaboration benefits would remain after a one-week delay, in both younger and older adults. Sixty younger (M age = 24.60) and 60 older (M age = 67.35) adults studied a list of words and then completed either two collaborative recall trials followed by two individual recall trials, or four individual recall trials. A five-min delay was inserted between the first three recall trials. The fourth recall trial was administered 1 week later. Collaborative recall was completed in groups of three individuals working together. Both younger and older adults benefitted from repeated collaborative recall trials to a greater extent than repeated individual recall trials, and such collaboration benefits remained after a one-week delay. This is the first demonstration of collaboration benefits on later individual recall at delays as long as 1 week, in both younger and older adults. Findings are discussed within the context of the negative effects of collaboration associated with group memory (collaborative inhibition) and the positive effects of collaboration associated with later individual memory (collaboration benefits). PMID:21264617

Short-term and long-term collaboration benefits on individual recall in younger and older adults.

PubMed

Blumen, Helena M; Stern, Yaakov

2011-01-01

A recent study of younger adults suggests that, compared to repeated individual recall trials, repeated collaborative recall trials produce better individual recall after a short delay (Blumen & Rajaram, 2008). Our study was designed to determine if such collaboration benefits would remain after a one-week delay, in both younger and older adults. Sixty younger (M age = 24.60) and 60 older (M age = 67.35) adults studied a list of words and then completed either two collaborative recall trials followed by two individual recall trials, or four individual recall trials. A five-min delay was inserted between the first three recall trials. The fourth recall trial was administered 1 week later. Collaborative recall was completed in groups of three individuals working together. Both younger and older adults benefitted from repeated collaborative recall trials to a greater extent than repeated individual recall trials, and such collaboration benefits remained after a one-week delay. This is the first demonstration of collaboration benefits on later individual recall at delays as long as 1 week, in both younger and older adults. Findings are discussed within the context of the negative effects of collaboration associated with group memory (collaborative inhibition) and the positive effects of collaboration associated with later individual memory (collaboration benefits).

Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

The 2010 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Consortium on Deaf-Blindness, 2011

2011-01-01

The National Child Count of Children and Youth who are Deaf-Blind is the first and longest running registry and knowledge base of children who are deaf-blind in the world. It represents a 25-plus year collaborative effort between the National Consortium on Deaf-Blindness (NCDB), its predecessors and each state deaf-blind project throughout the…

The 2008 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Consortium on Deaf-Blindness, 2009

2009-01-01

The "National Child Count of Children and Youth who are Deaf-Blind" is the first and longest running registry and knowledge base of children who are deaf-blind in the world. It represents a 25 year collaborative effort between the National Consortium on Deaf-Blindness (NCDB), its predecessors and each state/multi-state deaf-blind project…

Journeys in The Country of The Blind: Entanglement Theory and The Effects of Blinding on Trials of Homeopathy and Homeopathic Provings

PubMed Central

2007-01-01

The idea of quantum entanglement is borrowed from physics and developed into an algebraic argument to explain how double-blinding randomized controlled trials could lead to failure to provide unequivocal evidence for the efficacy of homeopathy, and inability to distinguish proving and placebo groups in homeopathic pathogenic trials. By analogy with the famous double-slit experiment of quantum physics, and more modern notions of quantum information processing, these failings are understood as blinding causing information loss resulting from a kind of quantum superposition between the remedy and placebo. PMID:17342236

Industry Collaboration and Primary Guest Authorship of High-Impact Randomized Clinical Trials: A Cross-Sectional Study.

PubMed

Roper, Nitin; Korenstein, Deborah

2015-10-01

Journals have increased disclosure requirements in recent years, in part to deter guest authorship. The prevalence of guest authorship among primary authors (first and last) in the current era of increased disclosure requirements is unknown. Our aim was to examine the self-reported prevalence of guest authorship among primary authors from a sample of randomized clinical trials with and without industry funding and industry collaboration in the design, analysis or reporting of trials. Cross-sectional analysis of randomized, drug/device clinical trials with published details on the "Role of the Funding Source/Sponsor" published in high-impact biomedical journals between 1 December 2011 and 31 November 2012. Phase 1 or 2 trials, secondary trial analyses, and trials that were not listed on ClinicalTrials.gov were excluded. Primary guest authorship was defined, based on International Committee of Medical Journal Editors (ICMJE) criteria, when neither the first nor last author contributed to either of the following: 1) the design of the trial or the analysis/interpretation of data; or 2) drafting part or all of the manuscript. One hundred and sixty-eight randomized clinical trials that met inclusion criteria were included. We measured differences in the prevalence of guest authorship between trials with neither industry funding nor collaboration and 1) trials with industry funding without collaboration, and 2) trials with industry funding with collaboration. The overall prevalence of primary guest authorship was 6 % (10/168). Primary guest authorship was significantly more common in trials with industry funding with collaboration than in those with neither industry funding nor collaboration [13.2 % (10/76) vs. 0 % (0/39); p < 0.02]. Primary guest authorship did not differ between trials with industry funding without collaboration and trials with neither industry funding nor collaboration. Among a sample of randomized, drug/device clinical trials in high-impact biomedical journals, primary guest authorship was overall uncommon and occurred exclusively among trials with industry funding with collaboration.

A generic minimization random allocation and blinding system on web.

PubMed

Cai, Hongwei; Xia, Jielai; Xu, Dezhong; Gao, Donghuai; Yan, Yongping

2006-12-01

Minimization is a dynamic randomization method for clinical trials. Although recommended by many researchers, the utilization of minimization has been seldom reported in randomized trials mainly because of the controversy surrounding the validity of conventional analyses and its complexity in implementation. However, both the statistical and clinical validity of minimization were demonstrated in recent studies. Minimization random allocation system integrated with blinding function that could facilitate the implementation of this method in general clinical trials has not been reported. SYSTEM OVERVIEW: The system is a web-based random allocation system using Pocock and Simon minimization method. It also supports multiple treatment arms within a trial, multiple simultaneous trials, and blinding without further programming. This system was constructed with generic database schema design method, Pocock and Simon minimization method and blinding method. It was coded with Microsoft Visual Basic and Active Server Pages (ASP) programming languages. And all dataset were managed with a Microsoft SQL Server database. Some critical programming codes were also provided. SIMULATIONS AND RESULTS: Two clinical trials were simulated simultaneously to test the system's applicability. Not only balanced groups but also blinded allocation results were achieved in both trials. Practical considerations for minimization method, the benefits, general applicability and drawbacks of the technique implemented in this system are discussed. Promising features of the proposed system are also summarized.

Minnesota Deaf-Blind Technical Assistance Project. Final Report.

ERIC Educational Resources Information Center

Kloos, Eric

This final report describes activities and accomplishments of the 3-year federally supported Minnesota Deaf-Blind Technical Assistance Project. The project provided training and technical assistance, information sharing, and support services to families of children with deaf-blindness. Activities and accomplishments included: collaboration with…

Implementation and evaluation of the 5As framework of obesity management in primary care: design of the 5As Team (5AsT) randomized control trial

PubMed Central

2014-01-01

Background Obesity is a pressing public health concern, which frequently presents in primary care. With the explosive obesity epidemic, there is an urgent need to maximize effective management in primary care. The 5As of Obesity Management™ (5As) are a collection of knowledge tools developed by the Canadian Obesity Network. Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable. The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team (5AsT) intervention to change provider behaviour. Methods/design The 5AsT trial is a theoretically informed, pragmatic randomized controlled trial with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP, mental health, dietitians) will be randomized to control or the 5AsT intervention group, to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation. The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care. Evidence-based shared decision making tools will be co-developed and iteratively tested by practitioners. Evaluation will be informed by the RE-AIM framework. The primary outcome measure, to which participants are blinded, is number of weight management visits/full-time equivalent (FTE) position. Patient-level outcomes will also be assessed, through a longitudinal cohort study of patients from randomized practices. Patient outcomes include clinical (e.g., body mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D), and satisfaction with care. Qualitative data collected from providers and patients will be evaluated using thematic analysis to understand the context, implementation and effectiveness of the 5AsT program. Discussion The 5AsT trial will provide a wide range of insights into current practices, knowledge gaps and barriers that limit obesity management in primary practice. The use of existing resources, collaborative design, practice facilitation, and integrated feedback loops cultivate an applicable, adaptable and sustainable approach to increasing the quantity and quality of weight management visits in primary care. Trial registration NCT01967797. PMID:24947045

Deaf-Blind Perspectives, Fall 1994-Spring 1995.

ERIC Educational Resources Information Center

Deaf-Blind Perspectives, 1995

1995-01-01

This document consists of the three second-year issues of a newsletter concerning people with deaf-blindness. These issues include the following major articles: "A Report on Deaf-Blind Technical Assistance Collaboration" (Paddi Henderson and Rich Mulholland); "Rabbits and Retards" (Joyce Ford), in which a parent describes an…

BLIND TRIALS EVALUATING IN VITRO INFECTIVITY OF CRYPTOSPORIDIUM PARVUM OOCYSTS USING CELL CULTURE IMMUNOFLUORESCENCE

EPA Science Inventory

An optimized cell culture-immunofluorescence (IFA) procedure, using the HCT-8 cell line, was evaluated in 'blind' trials to determine the sensitivity and reproducibility for measuring infectivity of flow cytometry prepared inocula of C. parvum oocysts. In separate trials, suspens...

Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network.

PubMed

Newton, Katherine M; Carpenter, Janet S; Guthrie, Katherine A; Anderson, Garnet L; Caan, Bette; Cohen, Lee S; Ensrud, Kristine E; Freeman, Ellen W; Joffe, Hadine; Sternfeld, Barbara; Reed, Susan D; Sherman, Sheryl; Sammel, Mary D; Kroenke, Kurt; Larson, Joseph C; Lacroix, Andrea Z

2014-01-01

This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ω-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed. The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.

A Remote Collaborative Care Program for Patients with Depression Living in Rural Areas: Open-Label Trial.

PubMed

Rojas, Graciela; Guajardo, Viviana; Martínez, Pablo; Castro, Ariel; Fritsch, Rosemarie; Moessner, Markus; Bauer, Stephanie

2018-04-30

In the treatment of depression, primary care teams have an essential role, but they are most effective when inserted into a collaborative care model for disease management. In rural areas, the shortage of specialized mental health resources may hamper management of depressed patients. The aim was to test the feasibility, acceptability, and effectiveness of a remote collaborative care program for patients with depression living in rural areas. In a nonrandomized, open-label (blinded outcome assessor), two-arm clinical trial, physicians from 15 rural community hospitals recruited 250 patients aged 18 to 70 years with a major depressive episode (DSM-IV criteria). Patients were assigned to the remote collaborative care program (n=111) or to usual care (n=139). The remote collaborative care program used Web-based shared clinical records between rural primary care teams and a specialized/centralized mental health team, telephone monitoring of patients, and remote supervision by psychiatrists through the Web-based shared clinical records and/or telephone. Depressive symptoms, health-related quality of life, service use, and patient satisfaction were measured 3 and 6 months after baseline assessment. Six-month follow-up assessments were completed by 84.4% (221/250) of patients. The remote collaborative care program achieved higher user satisfaction (odds ratio [OR] 1.94, 95% CI 1.25-3.00) and better treatment adherence rates (OR 1.81, 95% CI 1.02-3.19) at 6 months compared to usual care. There were no statically significant differences in depressive symptoms between the remote collaborative care program and usual care. Significant differences between groups in favor of remote collaborative care program were observed at 3 months for mental health-related quality of life (beta 3.11, 95% CI 0.19-6.02). Higher rates of treatment adherence in the remote collaborative care program suggest that technology-assisted interventions may help rural primary care teams in the management of depressive patients. Future cost-effectiveness studies are needed. Clinicaltrials.gov NCT02200367; https://clinicaltrials.gov/ct2/show/NCT02200367 (Archived by WebCite at http://www.webcitation.org/6xtZ7OijZ). ©Graciela Rojas, Viviana Guajardo, Pablo Martínez, Ariel Castro, Rosemarie Fritsch, Markus Moessner, Stephanie Bauer. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.04.2018.

Uganda gets set for vaccine trials, but the ethical debate continues.

PubMed

1997-04-01

An HIV vaccine trial scheduled for 1997 involves 2000 male and female members of the Uganda People's Defence Force. The volunteers are 18-40 years old and have been evaluated for 18 months. The trial of Alvac-HIV vaccine developed by Pasteur Manieux Connaught will be conducted by the Joint Clinical Research Council, a joint venture of Makerere University and the Ministries of Health and Defence, in collaboration with the Johns Hopkins University. The vaccine has already been tested on 300 volunteers in France and the US. The initial stage of testing will involve a randomized, placebo-controlled, double-blind trial comparing the safety and immunogenicity of four successive injections in 20 HIV-negative and 20 HIV-positive volunteers. Follow-up will continue for a year. While volunteers will get free medical attention if they develop a severe reaction to the vaccine and will receive a full explanation about the experimental nature of the vaccine, it has not been determined how volunteers will be compensated if something unforeseen goes wrong. Additional concerns revolve around Uganda's readiness to institute proper legal controls and ethical standards in cases of biomedical research.

A quantum-like model of homeopathy clinical trials: importance of in situ randomization and unblinding.

PubMed

Beauvais, Francis

2013-04-01

The randomized controlled trial (RCT) is the 'gold standard' of modern clinical pharmacology. However, for many practitioners of homeopathy, blind RCTs are an inadequate research tool for testing complex therapies such as homeopathy. Classical probabilities used in biological sciences and in medicine are only a special case of the generalized theory of probability used in quantum physics. I describe homeopathy trials using a quantum-like statistical model, a model inspired by quantum physics and taking into consideration superposition of states, non-commuting observables, probability interferences, contextuality, etc. The negative effect of blinding on success of homeopathy trials and the 'smearing effect' ('specific' effects of homeopathy medicine occurring in the placebo group) are described by quantum-like probabilities without supplementary ad hoc hypotheses. The difference of positive outcome rates between placebo and homeopathy groups frequently vanish in centralized blind trials. The model proposed here suggests a way to circumvent such problems in masked homeopathy trials by incorporating in situ randomization/unblinding. In this quantum-like model of homeopathy clinical trials, success in open-label setting and failure with centralized blind RCTs emerge logically from the formalism. This model suggests that significant differences between placebo and homeopathy in blind RCTs would be found more frequently if in situ randomization/unblinding was used. Copyright © 2013. Published by Elsevier Ltd.

Simulation-Based Abdominal Ultrasound Training - A Systematic Review.

PubMed

Østergaard, M L; Ewertsen, C; Konge, L; Albrecht-Beste, E; Bachmann Nielsen, M

2016-06-01

The aim is to provide a complete overview of the different simulation-based training options for abdominal ultrasound and to explore the evidence of their effect. This systematic review was performed according to the PRISMA guidelines and Medline, Embase, Web of Science, and the Cochrane Library was searched. Articles were divided into three categories based on study design (randomized controlled trials, before-and-after studies and descriptive studies) and assessed for level of evidence using the Oxford Centre for Evidence Based Medicine (OCEBM) system and for bias using the Cochrane Collaboration risk of bias assessment tool. Seventeen studies were included in the analysis: four randomized controlled trials, eight before-and-after studies with pre- and post-test evaluations, and five descriptive studies. No studies scored the highest level of evidence, and 14 had the lowest level. Bias was high for 11 studies, low for four, and unclear for two. No studies used a test with established evidence of validity or examined the correlation between obtained skills on the simulators and real-life clinical skills. Only one study used blinded assessors. The included studies were heterogeneous in the choice of simulator, study design, participants, and outcome measures, and the level of evidence for effect was inadequate. In all studies simulation training was equally or more beneficial than other instructions or no instructions. Study designs had significant built-in bias and confounding issues; therefore, further research should be based on randomized controlled trials using tests with validity evidence and blinded assessors. © Georg Thieme Verlag KG Stuttgart · New York.

The 2009 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Consortium on Deaf-Blindness, 2010

2010-01-01

The National Child Count of Children and Youth who are Deaf-Blind is the first and longest running registry and knowledge base of children who are deaf-blind in the world. It represents a 25 year collaborative effort between NCDB, its predecessors and each state deaf-blind project throughout the country, as well as those projects funded in the…

The 2012 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Consortium on Deaf-Blindness, 2013

2013-01-01

The National Child Count of Children and Youth who are Deaf-Blind is the first and longest running registry and knowledge base of children who are deaf-blind in the world. Begun in 1986 on behalf of the U.S. Department of Education, it represents a nearly thirty year collaborative effort between the National Consortium on Deaf-Blindness (NCDB),…

The 2014 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Center on Deaf-Blindness, 2015

2015-01-01

The National Child Count of Children and Youth who are Deaf-Blind is the first and longest running registry and knowledge base of children who are deaf-blind in the world. Begun in 1986 on behalf of the U.S. Department of Education, it represents a nearly thirty year collaborative effort between the National Center on Deaf-Blindness (NCDB), its…

Dog models for blinding inherited retinal dystrophies.

PubMed

Petersen-Jones, Simon M; Komáromy, András M

2015-03-01

Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Study protocol for a cluster randomised controlled trial to assess the effectiveness of user-driven intervention to prevent aggressive events in psychiatric services.

PubMed

Välimäki, Maritta; Yang, Min; Normand, Sharon-Lise; Lorig, Kate R; Anttila, Minna; Lantta, Tella; Pekurinen, Virve; Adams, Clive E

2017-04-04

People admitted to psychiatric hospitals with a diagnosis of schizophrenia may display behavioural problems. These may require management approaches such as use of coercive practices, which impact the well-being of staff members, visiting families and friends, peers, as well as patients themselves. Studies have proposed that not only patients' conditions, but also treatment environment and ward culture may affect patients' behaviour. Seclusion and restraint could possibly be prevented with staff education about user-centred, more humane approaches. Staff education could also increase collaboration between patients, family members and staff, which may further positively affect treatment culture and lower the need for using coercive treatment methods. This is a single-blind, two-arm cluster randomised controlled trial involving 28 psychiatric hospital wards across Finland. Units will be randomised to receive either a staff educational programme delivered by the team of researchers, or standard care. The primary outcome is the incidence of use of patient seclusion rooms, assessed from the local/national health registers. Secondary outcomes include use of other coercive methods (limb restraint, forced injection, and physical restraint), service use, treatment satisfaction, general functioning among patients, and team climate and employee turn-over (nursing staff). The study, designed in close collaboration with staff members, patients and their relatives, will provide evidence for a co-operative and user-centred educational intervention aiming to decrease the prevalence of coercive methods and service use in the units, increase the functional status of patients and improve team climate in the units. We have identified no similar trials. ClinicalTrials.gov NCT02724748 . Registered on 25 th of April 2016.

The superiority in voice processing of the blind arises from neural plasticity at sensory processing stages.

PubMed

Föcker, Julia; Best, Anna; Hölig, Cordula; Röder, Brigitte

2012-07-01

Blind people rely much more on voices compared to sighted individuals when identifying other people. Previous research has suggested a faster processing of auditory input in blind individuals than sighted controls and an enhanced activation of temporal cortical regions during voice processing. The present study used event-related potentials (ERPs) to single out the sub-processes of auditory person identification that change and allow for superior voice processing after congenital blindness. A priming paradigm was employed in which two successive voices (S1 and S2) of either the same (50% of the trials) or different actors were presented. Congenitally blind and matched sighted participants made an old-young decision on the S2. During the pre-experimental familiarization with the stimuli, congenitally blind individuals showed faster learning rates than sighted controls. Reaction times were shorter in person-congruent trials than in person-incongruent trials in both groups. ERPs to S2 stimuli in person-incongruent as compared to person-congruent trials were significantly enhanced at early processing stages (100-160 ms) in congenitally blind participants only. A later negative ERP effect (>200 ms) was found in both groups. The scalp topographies of the experimental effects were characterized by a central and parietal distribution in the sighted but a more posterior distribution in the congenitally blind. These results provide evidence for an improvement of early voice processing stages and a reorganization of the person identification system as a neural correlate of compensatory behavioral improvements following congenital blindness. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dog Models for Blinding Inherited Retinal Dystrophies

PubMed Central

Komáromy, András M.

2015-01-01

Abstract Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials. PMID:25671556

Implementation and evaluation of the 5As framework of obesity management in primary care: design of the 5As Team (5AsT) randomized control trial.

PubMed

Campbell-Scherer, Denise L; Asselin, Jodie; Osunlana, Adedayo M; Fielding, Sheri; Anderson, Robin; Rueda-Clausen, Christian F; Johnson, Jeffrey A; Ogunleye, Ayodele A; Cave, Andrew; Manca, Donna; Sharma, Arya M

2014-06-19

Obesity is a pressing public health concern, which frequently presents in primary care. With the explosive obesity epidemic, there is an urgent need to maximize effective management in primary care. The 5As of Obesity Management™ (5As) are a collection of knowledge tools developed by the Canadian Obesity Network. Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable. The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team (5AsT) intervention to change provider behaviour. The 5AsT trial is a theoretically informed, pragmatic randomized controlled trial with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP, mental health, dietitians) will be randomized to control or the 5AsT intervention group, to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation. The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care. Evidence-based shared decision making tools will be co-developed and iteratively tested by practitioners. Evaluation will be informed by the RE-AIM framework. The primary outcome measure, to which participants are blinded, is number of weight management visits/full-time equivalent (FTE) position. Patient-level outcomes will also be assessed, through a longitudinal cohort study of patients from randomized practices. Patient outcomes include clinical (e.g., body mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D), and satisfaction with care. Qualitative data collected from providers and patients will be evaluated using thematic analysis to understand the context, implementation and effectiveness of the 5AsT program. The 5AsT trial will provide a wide range of insights into current practices, knowledge gaps and barriers that limit obesity management in primary practice. The use of existing resources, collaborative design, practice facilitation, and integrated feedback loops cultivate an applicable, adaptable and sustainable approach to increasing the quantity and quality of weight management visits in primary care. NCT01967797.

Commentary on Reconstituting Fibrinogen Concentrate to Maintain Blinding in a Double-blind, Randomized Trial in an Emergency Setting.

PubMed

Bruynseels, Daniel; Solomon, Cristina; Hallam, Angela; Collins, Peter W; Collis, Rachel E; Hamlyn, Vincent; Hall, Judith E

2016-01-01

The gold standard of trial design is the double-blind, placebo-controlled, randomized trial. Intravenous medication, which needs reconstitution by the attending clinician in an emergency situation, can be challenging to incorporate into a suitably blinded study. We have developed a method of blindly reconstituting and administering fibrinogen concentrate (presented as a lyophilized powder), where the placebo is normal saline. Fibrinogen concentrate is increasingly being used early in the treatment of major hemorrhage. Our methodology was designed for a multicenter study investigating the role of fibrinogen concentrate in the treatment of the coagulopathy associated with major obstetric hemorrhage. The method has been verified by a stand-alone pharmaceutical manufacturing unit with an investigational medicinal products license, and to date has successfully been applied 45 times in four study centers. There have been no difficulties in reconstitution and no related adverse events reported. We feel our method is simple to perform and maintains blinding throughout, making it potentially suitable for use in other trials conducted in psychologically high-pressure environments. Although fibrinogen concentrate was the focus of our study, it is likely that the method is applicable to other lyophilized medication with limited shelf life (e.g., antibiotics). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review).

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2013-07-01

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There is a need for large, randomised controlled trials for this serious condition. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

International collaborative study of the endogenous reference gene, sucrose phosphate synthase (SPS), used for qualitative and quantitative analysis of genetically modified rice.

PubMed

Jiang, Lingxi; Yang, Litao; Zhang, Haibo; Guo, Jinchao; Mazzara, Marco; Van den Eede, Guy; Zhang, Dabing

2009-05-13

One rice ( Oryza sativa ) gene, sucrose phosphate synthase (SPS), has been proven to be a suitable endogenous reference gene for genetically modified (GM) rice detection in a previous study. Herein are the reported results of an international collaborative ring trial for validation of the SPS gene as an endogenous reference gene and its optimized qualitative and quantitative polymerase chain reaction (PCR) systems. A total of 12 genetically modified organism (GMO) detection laboratories from seven countries participated in the ring trial and returned their results. The validated results confirmed the species specificity of the method through testing 10 plant genomic DNAs, low heterogeneity, and a stable single-copy number of the rice SPS gene among 7 indica varieties and 5 japonica varieties. The SPS qualitative PCR assay was validated with a limit of detection (LOD) of 0.1%, which corresponded to about 230 copies of haploid rice genomic DNA, while the limit of quantification (LOQ) for the quantitative PCR system was about 23 copies of haploid rice genomic DNA, with acceptable PCR efficiency and linearity. Furthermore, the bias between the test and true values of eight blind samples ranged from 5.22 to 26.53%. Thus, we believe that the SPS gene is suitable for use as an endogenous reference gene for the identification and quantification of GM rice and its derivates.

Randomized trial of teaching brief motivational interviewing to pediatric trainees to promote healthy behaviors in families.

PubMed

Lozano, Paula; McPhillips, Heather A; Hartzler, Bryan; Robertson, Andrea S; Runkle, Cecilia; Scholz, Kelley A; Stout, James W; Kieckhefer, Gail M

2010-06-01

That pediatric resident trainees would demonstrate increased counseling skill following training in brief motivational interviewing (MI). Randomized controlled trial. University of Washington Pediatric Residency. Pediatric residents (N = 18), including residents in postgraduate years 1, 2, 3, and 4. Collaborative Management in Pediatrics, a 9-hour behavior change curriculum based on brief MI plus written feedback on communication skills (based on a 3-month Objective Standardized Clinical Evaluation [OSCE]). The percentage of MI-consistent behavior (%MICO), a summary score for MI skill, was assessed via OSCEs in which standardized patients portray parents of children with asthma in 3 clinical scenarios (stations). The OSCEs were conducted at baseline and 3 and 7 months. Blinded coders rated videotaped OSCEs using a validated tool to tally communication behaviors. Training effects were assessed using linear regression controlling for baseline %MICO. Global ratings of counseling style served as secondary outcome measures. Trained residents demonstrated a trend toward increased skill (%MICO score) at 3 months compared with control residents. At 7 months, %MICO scores increased 16% to 20% (P < .02) across all OSCE stations after the combined intervention of Collaborative Management in Pediatrics training plus written feedback. The effect of training on global ratings supported the main findings. Pediatric trainees' skills in behavior change counseling improved following the combination of training in brief MI plus personalized feedback.

Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.

PubMed

Llewellyn-Jones, R H; Baikie, K A; Smithers, H; Cohen, J; Snowdon, J; Tennant, C C

1999-09-11

To evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care. Randomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months. Population of residential facility in Sydney living in self care units and hostels. 220 depressed residents aged >/=65 without severe cognitive impairment. The shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care. Geriatric depression scale. Intention to treat analysis was used. There was significantly more movement to "less depressed" levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011). The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.

The 2013 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Center on Deaf-Blindness, 2014

2014-01-01

The National Child Count of Children and Youth who are Deaf-Blind is the first and longest running registry and knowledge base of children who are deaf-blind in the world. It has been collaboratively designed, implemented and revised to serve as the common vehicle to meet federal grant requirements for both the State/Multi-State and National…

The 2011 National Child Count of Children and Youth Who Are Deaf-Blind

ERIC Educational Resources Information Center

National Consortium on Deaf-Blindness, 2012

2012-01-01

The National Child Count of Children and Youth who are Deaf-Blind is the first and longest running registry and knowledge base of children who are deaf-blind in the world. Begun in 1986 on behalf of the U.S. Department of Education (Baldwin, 1993), it represents a thirty plus year collaborative effort between the National Consortium on…

Improving Cancer Outcomes Through International Collaboration in Academic Cancer Treatment Trials

PubMed Central

Trimble, Edward L.; Abrams, Jeffrey S.; Meyer, Ralph M.; Calvo, Fabien; Cazap, Eduardo; Deye, James; Eisenhauer, Elizabeth; Fitzgerald, Thomas J.; Lacombe, Denis; Parmar, Max; Seibel, Nita; Shankar, Lalitha; Swart, Ann Marie; Therasse, Patrick; Vikram, Bhadrasain; von Frenckell, Remy; Friedlander, Michael; Fujiwara, Keiichi; Kaplan, Richard S.; Meunier, Francoise

2009-01-01

Purpose The need for international collaboration in cancer clinical trials has grown stronger as we have made progress both in cancer treatment and screening. We sought to identify those efforts already underway which facilitate such collaboration, as well as barriers to greater collaboration. Methods We reviewed the collective experiences of many cooperative groups, governmental organizations, nongovernmental organizations, and academic investigators in their work to build international collaboration in cancer clinical trials across multiple disease sites. Results More than a decade of work has led to effective global harmonization for many of the elements critical to cancer clinical trials. Many barriers remain, but effective international collaboration in academic cancer treatment trials should become the norm, rather than the exception. Conclusion Our ability to strengthen international collaborations will result in maximization of our resources and patients, permitting us to change practice by establishing more effective therapeutic strategies. Regulatory, logistical, and financial hurdles, however, often hamper the conduct of joint trials. We must work together as a global community to overcome these barriers so that we may continue to improve cancer treatment for patients around the world. PMID:19720905

Implementation of an Ebola virus disease vaccine clinical trial during the Ebola epidemic in Liberia: Design, procedures, and challenges.

PubMed

Kennedy, Stephen B; Neaton, James D; Lane, H Clifford; Kieh, Mark W S; Massaquoi, Moses B F; Touchette, Nancy A; Nason, Martha C; Follmann, Dean A; Boley, Fatorma K; Johnson, Melvin P; Larson, Gregg; Kateh, Francis N; Nyenswah, Tolbert G

2016-02-01

The index case of the Ebola virus disease epidemic in West Africa is believed to have originated in Guinea. By June 2014, Guinea, Liberia, and Sierra Leone were in the midst of a full-blown and complex global health emergency. The devastating effects of this Ebola epidemic in West Africa put the global health response in acute focus for urgent international interventions. Accordingly, in October 2014, a World Health Organization high-level meeting endorsed the concept of a phase 2/3 clinical trial in Liberia to study Ebola vaccines. As a follow-up to the global response, in November 2014, the Government of Liberia and the US Government signed an agreement to form a research partnership to investigate Ebola and to assess intervention strategies for treating, controlling, and preventing the disease in Liberia. This agreement led to the establishment of the Joint Liberia-US Partnership for Research on Ebola Virus in Liberia as the beginning of a long-term collaborative partnership in clinical research between the two countries. In this article, we discuss the methodology and related challenges associated with the implementation of the Ebola vaccines clinical trial, based on a double-blinded randomized controlled trial, in Liberia. © The Author(s) 2016.

Monitoring potential adverse event rate differences using data from blinded trials: the canary in the coal mine.

PubMed

Gould, A Lawrence; Wang, William B

2017-01-15

The development of drugs and biologicals whose mechanisms of action may extend beyond their target indications has led to a need to identify unexpected potential toxicities promptly even while blinded clinical trials are under way. One component of recently issued FDA rules regarding safety reporting requirements raises the possibility of breaking the blind for pre-identified serious adverse events that are not the clinical endpoints of a blinded study. Concern has been expressed that unblinding individual cases of frequently occurring adverse events could compromise the overall validity of the study. However, if external information is available about adverse event rates among patients not receiving the test product in populations similar to the study population, then it may be possible to address the potential for elevated risk without unblinding the trial. This article describes a Bayesian approach for determining the likelihood of elevated risk suitable binomial or Poisson likelihoods that applies regardless of the metric used to express the difference. The method appears to be particularly appropriate for routine monitoring of safety information for project development programs that include large blinded trials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

PubMed

Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

2015-09-01

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

Collaborative care for depression and anxiety disorders in patients with recent cardiac events: the Management of Sadness and Anxiety in Cardiology (MOSAIC) randomized clinical trial.

PubMed

Huffman, Jeff C; Mastromauro, Carol A; Beach, Scott R; Celano, Christopher M; DuBois, Christina M; Healy, Brian C; Suarez, Laura; Rollman, Bruce L; Januzzi, James L

2014-06-01

Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events. There has been minimal study of collaborative care (CC) management models for mental health disorders in high-risk cardiac inpatients, and no prior CC intervention has simultaneously managed depression and anxiety disorders. To determine the impact of a low-intensity CC intervention for depression, generalized anxiety disorder, and panic disorder among patients hospitalized for an acute cardiac illness. Single-blind randomized clinical trial, with study assessors blind to group assignment, from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome, arrhythmia, or heart failure and found to have clinical depression, generalized anxiety disorder, or panic disorder on structured assessment. Participants were randomized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders (n = 92) or to enhanced usual care (serial notification of primary medical providers; n = 91). The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate. Improvement in mental health-related quality of life (Short Form-12 Mental Component Score [SF-12 MCS]) at 24 weeks, compared between groups using a random-effects model in an intent-to-treat analysis. Patients randomized to CC had significantly greater estimated mean improvements in SF-12 MCS at 24 weeks (11.21 points [from 34.21 to 45.42] in the CC group vs 5.53 points [from 36.30 to 41.83] in the control group; estimated mean difference, 5.68 points [95% CI, 2.14-9.22]; P = .002; effect size, 0.61). Patients receiving CC also had significant improvements in depressive symptoms and general functioning, and higher rates of treatment of a mental health disorder; anxiety scores, rates of disorder response, and adherence did not differ between groups. A novel telephone-based, low-intensity model to concurrently manage cardiac patients with depression and/or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial. clinicaltrials.gov Identifier: NCT01201967.

The 2015 National Child Count of Children and Youth Who Are Deaf-Blind Report

ERIC Educational Resources Information Center

National Center on Deaf-Blindness, 2016

2016-01-01

This, the 30th annual "National Child Count of Children and Youth Who Are Deaf-Blind," is the first and longest running registry and knowledge base of children who are deaf-blind in the world. Begun in 1986 on behalf of the U.S. Department of Education, it represents a nearly thirty year collaborative effort between the National Center…

Brain Tumor Trials Collaborative | Center for Cancer Research

Cancer.gov

Brain Tumor Trials Collaborative In Pursuit of a Cure The mission of the BTTC is to develop and perform state-of-the-art clinical trials in a collaborative and collegial environment, advancing treatments for patients with brain tumors, merging good scientific method with concern for patient well-being and outcome.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: Double-blind randomized crossover clinical trial in post-menopausal women

USDA-ARS?s Scientific Manuscript database

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (C...

The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders

PubMed Central

Jensen, Matthew B.; Janik, Erika L.; Waclawik, Andrew J.

2016-01-01

We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses. PMID:27617324

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP.

PubMed

de Heer, Eric W; Dekker, Jack; van Eck van der Sluijs, Jonna F; Beekman, Aartjan Tf; van Marwijk, Harm Wj; Holwerda, Tjalling J; Bet, Pierre M; Roth, Joost; Hakkaart-Van Roijen, Leona; Ringoir, Lianne; Kat, Fiona; van der Feltz-Cornelis, Christina M

2013-05-24

The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This study is a placebo controlled double blind, three armed randomized multi centre trial. Patients with (sub)chronic pain and a depressive disorder are randomized to either a) collaborative care with duloxetine, b) collaborative care with placebo or c) duloxetine alone. 189 completers are needed to attain sufficient power to show a clinically significant effect of 0.6 SD on the primary outcome measures (PHQ-9 score). Data on depression, anxiety, mental and physical health, medication adherence, medication tolerability, quality of life, patient-doctor relationship, coping, health resource use and productivity will be collected at baseline and after three, six, nine and twelve months. This study enables us to show the value of a closely monitored integrated treatment model above usual pharmacological treatment. Furthermore, a comparison with a placebo arm enables us to evaluate effectiveness of duloxetine in this population in a real life setting. Also, this study will provide evidence-based treatments and tools for their implementation in practice. This will facilitate generalization and implementation of results of this study. Moreover, patients included in this study are screened for pain symptoms, differentiating between nociceptive and neuropathic pain. Therefore, pain relief can be thoroughly evaluated. NTR1089.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

PubMed

Zannad, Faiez; Pfeffer, Marc A; Bhatt, Deepak L; Bonds, Denise E; Borer, Jeffrey S; Calvo-Rojas, Gonzalo; Fiore, Louis; Lund, Lars H; Madigan, David; Maggioni, Aldo Pietro; Meyers, Catherine M; Rosenberg, Yves; Simon, Tabassome; Stough, Wendy Gattis; Zalewski, Andrew; Zariffa, Nevine; Temple, Robert

2017-08-01

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease. © 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.

Trial of Propranolol in Children and Youth with ASD and Predictors of Response

DTIC Science & Technology

2017-07-01

youth) predicts treatment response. The design for both aims will be a double-blinded, placebo- controlled trial, 12 weeks in duration, with...the youth) predicts treatment response. The design for both aims will be a double-blinded, placebo- controlled trial, 12 weeks in duration, with...Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704

The risk of unblinding was infrequently and incompletely reported in 300 randomized clinical trial publications.

PubMed

Bello, Segun; Moustgaard, Helene; Hróbjartsson, Asbjørn

2014-10-01

To assess the proportion of clinical trials explicitly reporting the risk of unblinding, to evaluate the completeness of reporting on unblinding risk, and to describe the reported procedures involved in assessing unblinding. We sampled at random 300 blinded randomized clinical trials indexed in PubMed in 2010. Two authors read the trial publications and extracted data independently. Twenty-four trial publications, or 8% (95% confidence interval [CI], 5, 12%), explicitly reported the risk of unblinding, of which 16 publications, or 5% (95% CI, 3, 8%), reported compromised blinding; and 8 publications, or 3% (95% CI, 1, 5%), intact blinding. The reporting on risk of unblinding in the 24 trial publications was generally incomplete. The median proportion of assessments per trial affected by unblinding was 3% (range 1-30%). The most common mechanism for unblinding was perceptible physical properties of the treatments, for example, a difference in the taste and odor of a typhoid vaccine compared with its placebo. Published articles on randomized clinical trials infrequently reported risk of unblinding. This may reflect a tendency for avoiding reporting actual or suspected unblinding or a genuine low risk of unblinding. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of Menorrhagia with Tranexamic Acid. A Double-blind Trial

PubMed Central

Callender, Shei La T.; Warner, G. T.; Cope, E.

1970-01-01

In a double-blind trial tranexamic acid (Cyclokapron) 1 g. four times a day for the first four days of menstruation, significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found. No difference in side-effects was noted between the active and placebo treatment. PMID:4919554

Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Munasinghe, Sujeeva A.; Oliff, Carolyn; Finn, Judith; Wray, John A.

2010-01-01

To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating…

Guiding Blind Pedestrians with a Personal Navigation System

NASA Astrophysics Data System (ADS)

Dodson, A. H.; Moon, G. V.; Moore, T.; Jones, D.

With the assistance provided by the white cane or guide dog, most blind pedestrians can find their way to known destinations along familiar routes. Finding new or known destinations along unfamiliar routes is more challenging. Before such a journey is attempted, detailed instructions must be acquired. The difficulty of obtaining and then reliably following such instructions deters many blind pedestrians from travelling alone in unknown areas. This paper demonstrates a technological approach, by way of field trials, that supplements the existing aids and eliminates the need for sighted guides. The approach has the potential to offer greater independence to the blind person. The investigation suggests that the methodology used in personal navigation systems for the sighted is sub-optimal for guiding the blind pedestrian. Suitable extensions are introduced, and the results show the proposed methodology is efficient for guiding the blind individual to unknown destinations in the chosen field trial environment.

Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia

PubMed Central

MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G

2014-01-01

Introduction Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). Methods and analysis FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. Ethics and dissemination FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. Trial Registration number FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728). PMID:25011991

Systematic evaluation of the methodology of randomized controlled trials of anticoagulation in patients with cancer.

PubMed

Rada, Gabriel; Schünemann, Holger J; Labedi, Nawman; El-Hachem, Pierre; Kairouz, Victor F; Akl, Elie A

2013-02-14

Randomized controlled trials (RCTs) that are inappropriately designed or executed may provide biased findings and mislead clinical practice. In view of recent interest in the treatment and prevention of thrombotic complications in cancer patients we evaluated the characteristics, risk of bias and their time trends in RCTs of anticoagulation in patients with cancer. We conducted a comprehensive search, including a search of four electronic databases (MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL) up to February 2010. We included RCTs in which the intervention and/or comparison consisted of: vitamin K antagonists, unfractionated heparin (UFH), low molecular weight heparin (LMWH), direct thrombin inhibitors or fondaparinux. We performed descriptive analyses and assessed the association between the variables of interest and the year of publication. We included 67 RCTs with 24,071 participants. In twenty one trials (31%) DVT diagnosis was triggered by clinical suspicion; the remaining trials either screened for DVT or were unclear about their approach. 41 (61%), 22 (33%), and 11 (16%) trials respectively reported on major bleeding, minor bleeding, and thrombocytopenia. The percentages of trials satisfying risk of bias criteria were: adequate sequence generation (85%), adequate allocation concealment (61%), participants' blinding (39%), data collectors' blinding (44%), providers' blinding (41%), outcome assessors' blinding (75%), data analysts' blinding (15%), intention to treat analysis (57%), no selective outcome reporting (12%), no stopping early for benefit (97%). The mean follow-up rate was 96%. Adequate allocation concealment and the reporting of intention to treat analysis were the only two quality criteria that improved over time. Many RCTs of anticoagulation in patients with cancer appear to use insufficiently rigorous outcome assessment methods and to have deficiencies in key methodological features. It is not clear whether this reflects a problem in the design, conduct or the reporting of these trials, or both. Future trials should avoid the shortcomings described in this article.

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.

Double-blind trials in hyperbaric medicine: A narrative review on past experiences and considerations in designing sham hyperbaric treatment.

PubMed

Lansdorp, C A; van Hulst, Rob A

2018-06-01

Background Hyperbaric oxygen therapy, which consists of breathing 100% oxygen under a higher atmospheric pressure than normal, is utilized worldwide in the treatment of several diseases. With the growing demand for evidence-based research, hyperbaric oxygen therapy has been criticized for delivering too little high-quality research, mainly in the form of randomized controlled trials. While not always indispensable, the addition of a sham-controlled group to such a trial can contribute to the quality of the research. However, the design of a sham (hyperbaric) treatment is associated with several considerations regarding adequate blinding and the use of pressure and oxygen. This narrative review discusses information on the sham profile and the blinding and safety of double-blind trials in hyperbaric medicine, irrespective of the indication for treatment. Methods MEDLINE, Embase and CENTRAL were searched for sham-controlled trials on hyperbaric oxygen therapy. The control treatment was considered sham if patients were blinded to their allocation and treatment took place in a hyperbaric chamber, with no restrictions regarding pressurization, oxygen levels or indication. Studies involving children or only one session of hyperbaric oxygen were excluded. Information on (the choice of) treatment profile, blinding measures, patient's perception regarding allocation and safety issues was extracted from eligible studies. Results A total of 42 eligible trials were included. The main strategies for sham treatment were (1) use of a lower pressure than that of the hyperbaric oxygen group, while breathing 21% oxygen; (2) use of the same pressure as the hyperbaric oxygen group, while breathing an adjusted percentage of oxygen; and (3) use of the same pressure as the hyperbaric oxygen group, while breathing 21% oxygen. The advantages and disadvantages of each strategy are discussed using the information provided by the trials. Conclusion Based on this review, using a lower pressure than the hyperbaric oxygen group while breathing 21% oxygen best matches the inertness of the placebo. Although studies show that use of a lower pressure does allow adequate blinding, this is associated with more practical issues than with the other strategies. The choice of which sham profile to use requires careful consideration; moreover, to ensure proper performance, a clear and detailed protocol is also required.

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

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

PubMed

Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

2017-05-03

The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

A Double-Blind, Randomized, Placebo-Controlled Trial of Escitalopram in the Treatment of Pediatric Depression

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Jonas, Jeffrey; Findling, Robert L.; Ventura, Daniel; Saikali, Khalil

2006-01-01

Objective: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. Method: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with…

20 CFR 404.1585 - Trial work period for persons age 55 or older who are blind.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Trial work period for persons age 55 or older who are blind. 404.1585 Section 404.1585 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL... activity that requires skills or abilities comparable to those required in the work you regularly did...

Blinded interpretation of study results can feasibly and effectively diminish interpretation bias.

PubMed

Järvinen, Teppo L N; Sihvonen, Raine; Bhandari, Mohit; Sprague, Sheila; Malmivaara, Antti; Paavola, Mika; Schünemann, Holger J; Guyatt, Gordon H

2014-07-01

Controversial and misleading interpretation of data from randomized trials is common. How to avoid misleading interpretation has received little attention. Herein, we describe two applications of an approach that involves blinded interpretation of the results by study investigators. The approach involves developing two interpretations of the results on the basis of a blinded review of the primary outcome data (experimental treatment A compared with control treatment B). One interpretation assumes that A is the experimental intervention and another assumes that A is the control. After agreeing that there will be no further changes, the investigators record their decisions and sign the resulting document. The randomization code is then broken, the correct interpretation chosen, and the manuscript finalized. Review of the document by an external authority before finalization can provide another safeguard against interpretation bias. We found the blinded preparation of a summary of data interpretation described in this article practical, efficient, and useful. Blinded data interpretation may decrease the frequency of misleading data interpretation. Widespread adoption of blinded data interpretation would be greatly facilitated were it added to the minimum set of recommendations outlining proper conduct of randomized controlled trials (eg, the Consolidated Standards of Reporting Trials statement). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress.

PubMed

Antic, Nick A; Heeley, Emma; Anderson, Craig S; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R Doug

2015-08-01

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. NCT00738179. ACTRN12608000409370. © 2015 Associated Professional Sleep Societies, LLC.

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955–2013

PubMed Central

Armijo-Olivo, Susan; Cummings, Greta G.; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

Objectives To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. Methods We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Results Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955–2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. Conclusions The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed. PMID:29272315

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955-2013.

PubMed

Saltaji, Humam; Armijo-Olivo, Susan; Cummings, Greta G; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955-2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed.

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

National Evaluation of the State Deaf-Blind Projects. NCEE 2018-4006

ERIC Educational Resources Information Center

Daley, Tamara C.; Edwards, Jessica; Fiore, Thomas A.; Johnson, Laura

2018-01-01

This report describes the work done by the 48 State Deaf-Blind Projects awarded grants by the Department of Education's Office of Special Education Programs (OSEP) in late 2013. The report documents the technical assistance and dissemination activities carried out by the Projects and their collaborative activities, describes the needs for…

Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Pandina, Gahan J.; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

2007-01-01

Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n =…

Blinded and unblinded internal pilot study designs for clinical trials with count data.

PubMed

Schneider, Simon; Schmidli, Heinz; Friede, Tim

2013-07-01

Internal pilot studies are a popular design feature to address uncertainties in the sample size calculations caused by vague information on nuisance parameters. Despite their popularity, only very recently blinded sample size reestimation procedures for trials with count data were proposed and their properties systematically investigated. Although blinded procedures are favored by regulatory authorities, practical application is somewhat limited by fears that blinded procedures are prone to bias if the treatment effect was misspecified in the planning. Here, we compare unblinded and blinded procedures with respect to bias, error rates, and sample size distribution. We find that both procedures maintain the desired power and that the unblinded procedure is slightly liberal whereas the actual significance level of the blinded procedure is close to the nominal level. Furthermore, we show that in situations where uncertainty about the assumed treatment effect exists, the blinded estimator of the control event rate is biased in contrast to the unblinded estimator, which results in differences in mean sample sizes in favor of the unblinded procedure. However, these differences are rather small compared to the deviations of the mean sample sizes from the sample size required to detect the true, but unknown effect. We demonstrate that the variation of the sample size resulting from the blinded procedure is in many practically relevant situations considerably smaller than the one of the unblinded procedures. The methods are extended to overdispersed counts using a quasi-likelihood approach and are illustrated by trials in relapsing multiple sclerosis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systemic therapy for vulval Erosive Lichen Planus (the 'hELP' trial): study protocol for a randomised controlled trial.

PubMed

Simpson, Rosalind C; Murphy, Ruth; Bratton, Daniel J; Sydes, Matthew R; Wilkes, Sally; Nankervis, Helen; Dowey, Shelley; Thomas, Kim S

2016-01-04

Erosive lichen planus affecting the vulva (ELPV) is a relatively rare, chronic condition causing painful raw areas in the vulvovaginal region. Symptoms are pain and burning, which impact upon daily living. There is paucity of evidence regarding therapy. A 2012 Cochrane systematic review found no randomised controlled trials (RCTs) in this field. Topically administered corticosteroids are the accepted first-line therapy: however, there is uncertainty as to which second-line treatments to use. Several systemic agents have been clinically noted to show promise for ELPV refractory to topically administered corticosteroids but there is no RCT evidence to support these. The 'hELP' study is a RCT with an internal pilot phase designed to provide high-quality evidence. The objective is to test whether systemic therapy in addition to standard topical therapy is a beneficial second-line treatment for ELPV. Adjunctive systemic therapies used are hydroxychloroquine, methotrexate, mycophenolate mofetil and prednisolone. Topical therapy plus a short course of prednisolone given orally is considered the comparator intervention. The trial is a four-armed, open-label, pragmatic RCT which uses a blinded independent clinical assessor. To provide 80 % power for each comparison, 96 participants are required in total. The pilot phase aims to recruit 40 participants. The primary clinical outcome is the proportion of patients achieving treatment success at 6 months. 'Success' is defined by a composite measure of Patient Global Assessment score of 0 or 1 on a 4-point scale plus improvement from baseline on clinical photographs scored by a clinician blinded to treatment allocation. Secondary clinical outcomes include 6-month assessment of: (1) Reduction in pain/soreness; (2) Global assessment of disease; (3) Response at other affected mucosal sites; (4) Hospital Anxiety and Depression Scale scores; (5) Sexual function; (6) Health-related quality of life using 'Short Form 36' and 'Skindex-29' questionnaires; (7) Days of topical steroid use; (8) Treatment satisfaction; (9) Discontinuation of medications due to treatment failure; (10) Per participant cost of intervention in each treatment group. Adverse events will also be reported. 'hELP' is the first RCT to address second-line treatment of ELPV. The trial has encountered unique methodological challenges and has required collaborative efforts of the UK Dermatology Clinical Trials Network alongside expert clinicians. ISRCTN 81883379 . Date of registration 12 June 2014.

Randomized controlled trials of simulation-based interventions in Emergency Medicine: a methodological review.

PubMed

Chauvin, Anthony; Truchot, Jennifer; Bafeta, Aida; Pateron, Dominique; Plaisance, Patrick; Yordanov, Youri

2018-04-01

The number of trials assessing Simulation-Based Medical Education (SBME) interventions has rapidly expanded. Many studies show that potential flaws in design, conduct and reporting of randomized controlled trials (RCTs) can bias their results. We conducted a methodological review of RCTs assessing a SBME in Emergency Medicine (EM) and examined their methodological characteristics. We searched MEDLINE via PubMed for RCT that assessed a simulation intervention in EM, published in 6 general and internal medicine and in the top 10 EM journals. The Cochrane Collaboration risk of Bias tool was used to assess risk of bias, intervention reporting was evaluated based on the "template for intervention description and replication" checklist, and methodological quality was evaluated by the Medical Education Research Study Quality Instrument. Reports selection and data extraction was done by 2 independents researchers. From 1394 RCTs screened, 68 trials assessed a SBME intervention. They represent one quarter of our sample. Cardiopulmonary resuscitation (CPR) is the most frequent topic (81%). Random sequence generation and allocation concealment were performed correctly in 66 and 49% of trials. Blinding of participants and assessors was performed correctly in 19 and 68%. Risk of attrition bias was low in three-quarters of the studies (n = 51). Risk of selective reporting bias was unclear in nearly all studies. The mean MERQSI score was of 13.4/18.4% of the reports provided a description allowing the intervention replication. Trials assessing simulation represent one quarter of RCTs in EM. Their quality remains unclear, and reproducing the interventions appears challenging due to reporting issues.

Collaboration, facilities and communities in day care services for older people.

PubMed

Adams, John

2001-05-01

Similarities and differences between day hospitals, run by the NHS, and day centres, run by local authorities or charitable organisations, have been widely discussed in the literature of gerontology for many years. The authors of this paper have undertaken a single blind, randomised-controlled trial to compare rehabilitation outcomes in the two settings, which was published in 1999. This research project involved augmenting the staff of day centres by visiting therapists. In addition to quantitative findings, their project also generated much qualitative data from interviews with health service and social service staff which provides the thought-provoking content. The themes identified included the reluctance of some patients to accept referral to a day centre, and the difficulties associated with discharging patients. Positive aspects included the opportunity to share skills, knowledge and resources. 29 references.

Clinical effectiveness and cost-effectiveness of collaborative care for depression in UK primary care (CADET): a cluster randomised controlled trial.

PubMed

Richards, David A; Bower, Peter; Chew-Graham, Carolyn; Gask, Linda; Lovell, Karina; Cape, John; Pilling, Stephen; Araya, Ricardo; Kessler, David; Barkham, Michael; Bland, J Martin; Gilbody, Simon; Green, Colin; Lewis, Glyn; Manning, Chris; Kontopantelis, Evangelos; Hill, Jacqueline J; Hughes-Morley, Adwoa; Russell, Abigail

2016-02-01

Collaborative care is effective for depression management in the USA. There is little UK evidence on its clinical effectiveness and cost-effectiveness. To determine the clinical effectiveness and cost-effectiveness of collaborative care compared with usual care in the management of patients with moderate to severe depression. Cluster randomised controlled trial. UK primary care practices (n = 51) in three UK primary care districts. A total of 581 adults aged ≥ 18 years in general practice with a current International Classification of Diseases, Tenth Edition depressive episode, excluding acutely suicidal people, those with psychosis, bipolar disorder or low mood associated with bereavement, those whose primary presentation was substance abuse and those receiving psychological treatment. Collaborative care: 14 weeks of 6-12 telephone contacts by care managers; mental health specialist supervision, including depression education, medication management, behavioural activation, relapse prevention and primary care liaison. Usual care was general practitioner standard practice. Blinded researchers collected depression [Patient Health Questionnaire-9 (PHQ-9)], anxiety (General Anxiety Disorder-7) and quality of life (European Quality of Life-5 Dimensions three-level version), Short Form questionnaire-36 items) outcomes at 4, 12 and 36 months, satisfaction (Client Satisfaction Questionnaire-8) outcomes at 4 months and treatment and service use costs at 12 months. In total, 276 and 305 participants were randomised to collaborative care and usual care respectively. Collaborative care participants had a mean depression score that was 1.33 PHQ-9 points lower [n = 230; 95% confidence interval (CI) 0.35 to 2.31; p = 0.009] than that of participants in usual care at 4 months and 1.36 PHQ-9 points lower (n = 275; 95% CI 0.07 to 2.64; p = 0.04) at 12 months after adjustment for baseline depression (effect size 0.28, 95% CI 0.01 to 0.52; odds ratio for recovery 1.88, 95% CI 1.28 to 2.75; number needed to treat 6.5). Quality of mental health but not physical health was significantly better for collaborative care at 4 months but not at 12 months. There was no difference for anxiety. Participants receiving collaborative care were significantly more satisfied with treatment. Differences between groups had disappeared at 36 months. Collaborative care had a mean cost of £272.50 per participant with similar health and social care service use between collaborative care and usual care. Collaborative care offered a mean incremental gain of 0.02 (95% CI -0.02 to 0.06) quality-adjusted life-years (QALYs) over 12 months at a mean incremental cost of £270.72 (95% CI -£202.98 to £886.04) and had an estimated mean cost per QALY of £14,248, which is below current UK willingness-to-pay thresholds. Sensitivity analyses including informal care costs indicated that collaborative care is expected to be less costly and more effective. The amount of participant behavioural activation was the only effect mediator. Collaborative care improves depression up to 12 months after initiation of the intervention, is preferred by patients over usual care, offers health gains at a relatively low cost, is cost-effective compared with usual care and is mediated by patient activation. Supervision was by expert clinicians and of short duration and more intensive therapy may have improved outcomes. In addition, one participant requiring inpatient treatment incurred very significant costs and substantially inflated our cost per QALY estimate. Future work should test enhanced intervention content not collaborative care per se. Current Controlled Trials ISRCTN32829227. This project was funded by the Medical Research Council (MRC) (G0701013) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.

Effects of pharmacological and nonpharmacological treatments on brain functional magnetic resonance imaging in Alzheimer's disease and mild cognitive impairment: a critical review.

PubMed

Canu, Elisa; Sarasso, Elisabetta; Filippi, Massimo; Agosta, Federica

2018-02-20

A growing number of pharmacological and nonpharmacological trials have been performed to test the efficacy of approved or experimental treatments in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context, functional magnetic resonance imaging (fMRI) may be a good candidate to detect brain changes after a short period of treatment. This critical review aimed to identify and discuss the available studies that have tested the efficacy of pharmacological and nonpharmacological treatments in AD and MCI cases using task-based or resting-state fMRI measures as primary outcomes. A PubMed-based literature search was performed with the use of the three macro-areas: 'disease', 'type of MRI', and 'type of treatment'. Each contribution was individually reviewed according to the Cochrane Collaboration's tool for assessing risk of bias. Study limitations were systematically detected and critically discussed. We selected 34 pharmacological and 13 nonpharmacological articles. According to the Cochrane Collaboration's tool for assessing risk of bias, 40% of these studies were randomized but only a few described clearly the randomization procedure, 36% declared the blindness of participants and personnel, and only 21% reported the blindness of outcome assessment. In addition, 28% of the studies presented more than 20% drop-outs at short- and/or long-term assessments. Additional common shortcomings of the reviewed works were related to study design, patient selection, sample size, choice of outcome measures, management of drop-out cases, and fMRI methods. There is an urgent need to obtain efficient treatments for AD and MCI. fMRI is powerful enough to detect even subtle changes over a short period of treatment; however, the soundness of methods should be improved to enable meaningful data interpretation.

Better early functional outcome after short stem total hip arthroplasty? A prospective blinded randomised controlled multicentre trial comparing the Collum Femoris Preserving stem with a Zweymuller straight cementless stem total hip replacement for the treatment of primary osteoarthritis of the hip

PubMed Central

van Oldenrijk, Jakob; Scholtes, Vanessa A B; van Beers, Loes W A H; Geerdink, Carel H; Niers, Bob B A M; Runne, Wouter; Bhandari, Mohit; Poolman, Rudolf W

2017-01-01

Objectives Primary aim was to compare the functional results at 3 months and 2 years between short and conventional cementless stem total hip arthroplasty (THA). Secondary aim was to determine the feasibility of a double-blind implant-related trial. Design A prospective blinded randomised controlled multicentre trial in patients with osteoarthritis of the hip. All patients, research assistants, clinical assessors, investigators and data analysts were blinded to the type of prosthesis. Population: 150 patients between 18 and 70 years with osteoarthritis of the hip, 75 in the short stem and 75 in the conventional stem group. Mean age: 60 years (SD 7). Interventions: the Collum Femoris Preserving short stem versus the Zweymuller Alloclassic conventional stem. Main outcome measures The Dutch version of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Secondary outcomes measures: Harris Hip Score, the Physical Component Scale of the SF12, the Timed Up and Go test, Pain and the EQ-5D. Feasibility outcomes: continued blinding, protocol adherence and follow-up success rate. Results No significant difference between the two groups. Mean HOOS total score in the short stem group increased 32.7 points from 36.6 (95% CI 32.9 to 40.2) preoperatively to 69.3 (95% CI 66.4 to 72.1) at 3 months follow-up. Mean HOOS total score in the conventional straight stem group increased 36.3 points from 37.1 (95% CI 33.9 to 40.3) preoperatively to 73.4 (95% CI 70.3 to 76.4) at 3 months follow-up. 91.2% of patients remained blinded at 2 years follow-up. Both protocol adherence and follow-up success rate were 98%. Conclusions Functional result at 3 months and 2 years after short stem THA is not superior to conventional cementless THA. There were more perioperative and postoperative complications in the short stem group. Direct comparison of two hip implants in a double-blinded randomised controlled trial is feasible. Trial registration number NTR1560. PMID:29042371

Back schools for nonspecific low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

PubMed

Heymans, M W; van Tulder, M W; Esmail, R; Bombardier, C; Koes, B W

2005-10-01

A systematic review within the Cochrane Collaboration Back Review Group. To assess the effectiveness of back schools for patients with nonspecific low back pain (LBP). Since the introduction of the Swedish back school in 1969, back schools have frequently been used for treating patients with LBP. However, the content of back schools has changed and appears to vary widely today. We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials to November 2004 for relevant trials reported in English, Dutch, French, or German. We also screened references from relevant reviews and included trials. Randomized controlled trials that reported on any type of back school for nonspecific LBP were included. Four reviewers, blinded to authors, institution, and journal, independently extracted the data and assessed the quality of the trials. We set the high-quality level, a priori, at a trial meeting six or more of 11 internal validity criteria. Because data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a qualitative review (best evidence synthesis) to summarize the results. The evidence was classified into four levels (strong, moderate, limited, or no evidence), taking into account the methodologic quality of the studies. We also evaluated the clinical relevance of the studies. Nineteen randomized controlled trials (3,584 patients) were included in this updated review. Overall, the methodologic quality was low, with only six trials considered to be high-quality. It was not possible to perform relevant subgroup analyses for LBP with radiation versus LBP without radiation. The results indicate that there is moderate evidence suggesting that back schools have better short- and intermediate-term effects on pain and functional status than other treatments for patients with recurrent and chronic LBP. There is moderate evidence suggesting that back schools for chronic LBP in an occupational setting are more effective than other treatments and placebo or waiting list controls on pain, functional status, and return to work during short- and intermediate-term follow-up. In general, the clinical relevance of the studies was rated as insufficient. There is moderate evidence suggesting that back schools, in an occupational setting, reduce pain and improve function and return-to-work status, in the short- and intermediate-term, compared with exercises, manipulation, myofascial therapy, advice, placebo, or waiting list controls, for patients with chronic and recurrent LBP. However, future trials should improve methodologic quality and clinical relevance and evaluate the cost-effectiveness of back schools.

Forward and Backward Repetition Blindness in Speed and Accuracy

ERIC Educational Resources Information Center

Wong, Kin Fai Ellick; Chen, Hsuan-Chih

2009-01-01

Repetition blindness (RB) was investigated in a new paradigm in which effects could stem from items preceding or following a target. Speeded-response tasks in which 3 critical items (C1, C2, and C3) were sequentially presented on each trial. In Experiments 1 and 2, participants were asked to judge whether C2 (the target) was present on each trial.…

Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

PubMed Central

Bonnevie, O; Svendsen, L B; Holst-Christensen, J; Johansen, T S; Søltoft, J; Christiansen, P M

1979-01-01

In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer. PMID:385457

Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis. 1989.

PubMed

Cannon, Grant W; Pincus, Seth H; Emkey, Ronald D; Denes, Alex; Cohen, Selwyn A; Wolfe, Frederick; Saway, P Anthony; Jaffer, Adrian M; Weaver, Arthur L; Cogen, Lewis; Schindler, John D

2008-02-01

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human gamma-interferon (rHu gamma-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHu gamma-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHu gamma-IFN was greater than that with placebo, the differences were generally not statistically significant.

Reporting characteristics and risk of bias in randomised controlled trials of acupuncture analgesia published in PubMed-listed journals.

PubMed

Li, Xiuxia; Wang, Rong; Shi, Xiue; Chen, Zehao; Pan, Yuanqing; Li, Xusheng; Yang, Kehu

2017-08-01

Acupuncture analgesia has been evaluated by a number of randomised controlled trials (RCTs); however, a systematic summary of reporting quality of RCTs in this specific field is lacking. To examine the reporting characteristics and risk of bias of RCTs of acupuncture analgesia indexed in the PubMed database. A PubMed search of RCTs of acupuncture analgesia was conducted through November 2015. The Cochrane Collaboration Risk of Bias Tool was used to assess the risk of bias of each trial. 206 articles were identified across 59 journals (impact factor 0.4-20), of which 56% of articles and 86% of journals were Science Citation Index (SCI)-indexed. Nearly half of the articles were published in China. The next most represented countries of origin were the UK (22%) and USA (21%). Of the included trials, postoperative pain was the most prevalent phenotype, and manual acupuncture was the most frequently applied type of stimulation (46%). A total of 12% of articles reported on analgesic mechanisms. The most frequently used acupuncture points were LI4, ST36, PC6, SP6 and Shenmen . The overwhelming majority of trials were considered to be at high risk of bias (84%). Furthermore, 79% of trials enrolled <50 participants per treatment arm. RCTs of acupuncture analgesia indexed in PubMed journals generally exhibited poor reporting of methodological and treatment details. Future studies should provide more information regarding clinical trial registration, blinding of participants (including sham procedures where applicable) and outcome assessors, as well as the training and qualification of acupuncturists. 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/.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Implementing collaborative primary care for depression and posttraumatic stress disorder: design and sample for a randomized trial in the U.S. military health system.

PubMed

Engel, Charles C; Bray, Robert M; Jaycox, Lisa H; Freed, Michael C; Zatzick, Doug; Lane, Marian E; Brambilla, Donald; Rae Olmsted, Kristine; Vandermaas-Peeler, Russ; Litz, Brett; Tanielian, Terri; Belsher, Bradley E; Evatt, Daniel P; Novak, Laura A; Unützer, Jürgen; Katon, Wayne J

2014-11-01

War-related trauma, posttraumatic stress disorder (PTSD), depression and suicide are common in US military members. Often, those affected do not seek treatment due to stigma and barriers to care. When care is sought, it often fails to meet quality standards. A randomized trial is assessing whether collaborative primary care improves quality and outcomes of PTSD and depression care in the US military health system. The aim of this study is to describe the design and sample for a randomized effectiveness trial of collaborative care for PTSD and depression in military members attending primary care. The STEPS-UP Trial (STepped Enhancement of PTSD Services Using Primary Care) is a 6 installation (18 clinic) randomized effectiveness trial in the US military health system. Study rationale, design, enrollment and sample characteristics are summarized. Military members attending primary care with suspected PTSD, depression or both were referred to care management and recruited for the trial (2592), and 1041 gave permission to contact for research participation. Of those, 666 (64%) met eligibility criteria, completed baseline assessments, and were randomized to 12 months of usual collaborative primary care versus STEPS-UP collaborative care. Implementation was locally managed for usual collaborative care and centrally managed for STEPS-UP. Research reassessments occurred at 3-, 6-, and 12-months. Baseline characteristics were similar across the two intervention groups. STEPS-UP will be the first large scale randomized effectiveness trial completed in the US military health system, assessing how an implementation model affects collaborative care impact on mental health outcomes. It promises lessons for health system change. Copyright © 2014 Elsevier Inc. All rights reserved.

CX-516 Cortex pharmaceuticals.

PubMed

Danysz, Wojciech

2002-07-01

CX-516 is one of a series of AMPA modulators under development by Cortex, in collaboration with Shire and Servier, for the potential treatment of Alzheimer's disease (AD), schizophrenia and mild cognitive impairment (MCI) [234221]. By June 2001, CX-516 was in phase II trials for both schizophrenia and attention deficit hyperactivity disorder (ADHD) [412513]. A phase II trial in fragile X syndrome and autism was expected to start in May 2002 [449861]. In October 2001, Cortex was awarded a Phase II SBIR grant of $769,818 from the National Institutes of Mental Health to investigate the therapeutic potential of AMPAkines in schizophrenia. This award was to support a phase IIb study of CX-516 as a combination therapy in schizophrenia patients concomitantly treated with olanzapine. The trial was to enroll 80 patients and employ a randomized, double-blind, placebo-controlled design in which the placebo group was to receive olanzapine plus placebo and the active group was to receive olanzapine plus CX-516 [425982]. In April 2000, Shire and Cortex signed an option agreement in which Shire was to evaluate CX-516for the treatment of ADHD. Under the terms of the agreement, Shire would undertake a double-blind, placebo-controlled evaluation of CX-516 involving ADHD patients. If the study proved effective, Shire would have the right to convert its option into an exclusive worldwide license for the AMPAkines for ADHD under a development and licensing agreement. Should Shire elect to execute this agreement, Shire would bear all future developmental costs [363618]. By February 2002, Cortex and Servier had revealed their intention to begin enrolment for an international study of an AMPAkine compound as a potential treatment for MCI in the near future. Assuming enrollment proceeded as anticipated, results were expected during the second quarter of 2003 [439301]. By May 2002, phase II trials were underway [450134]. In March 2002, Cortex was awarded extended funding under the University of California BioSTAR projectfor the research project: 'Ampakine modulation of brain neurotrophin expression: a novel therapeutic strategy'. This funding was expected to amount to $193,000 over a two-year period [444872].

A Randomized Clinical Trial of the Collaborative Assessment and Management of Suicidality vs. Enhanced Care as Usual for Sucidal Soldiers

DTIC Science & Technology

2017-06-01

Research Projects : Patient Perspectives on Successful Management of Suicide Risk in Military and Civilian Samples Masters Student: Kaitlyn R. Schuler...Award Number: W81XWH-11-1-0164 TITLE: "A Randomized Clinical Trial of the Collaborative Assessment & Management of Suicidality vs. Enhanced Care...REPORT TYPE Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE "A Randomized Clinical Trial of the Collaborative Assessment & Management

The effects of extrinsic motivation on signature authorship opinions in forensic signature blind trials.

PubMed

Dewhurst, Tahnee N; Found, Bryan; Ballantyne, Kaye N; Rogers, Doug

2014-03-01

Expertise studies in forensic handwriting examination involve comparisons of Forensic Handwriting Examiners' (FHEs) opinions with lay-persons on blind tests. All published studies of this type have reported real and demonstrable skill differences between the specialist and lay groups. However, critics have proposed that any difference shown may be indicative of a lack of motivation on the part of lay participants, rather than a real difference in skill. It has been suggested that qualified FHEs would be inherently more motivated to succeed in blinded validation trials, as their professional reputations could be at risk, should they perform poorly on the task provided. Furthermore, critics suggest that lay-persons would be unlikely to be highly motivated to succeed, as they would have no fear of negative consequences should they perform badly. In an effort to investigate this concern, a blind signature trial was designed and administered to forty lay-persons. Participants were required to compare known (exemplar) signatures of an individual to questioned signatures and asked to express an opinion regarding whether the writer of the known signatures wrote each of the questioned signatures. The questioned signatures comprised a mixture of genuine, disguised and simulated signatures. The forty participants were divided into two separate groupings. Group 'A' were requested to complete the trial as directed and were advised that for each correct answer they would be financially rewarded, for each incorrect answer they would be financially penalized, and for each inconclusive opinion they would receive neither penalty nor reward. Group 'B' was requested to complete the trial as directed, with no mention of financial recompense or penalty. The results of this study do not support the proposition that motivation rather than skill difference is the source of the statistical difference in opinions between individuals' results in blinded signature proficiency trials. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

Omega 3/6 Fatty Acids for Reading in Children: A Randomized, Double-Blind, Placebo-Controlled Trial in 9-Year-Old Mainstream Schoolchildren in Sweden

ERIC Educational Resources Information Center

Johnson, Mats; Fransson, Gunnar; Östlund, Sven; Areskoug, Björn; Gillberg, Christopher

2017-01-01

Background: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. Methods: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active…

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: A double-blind randomized controlled trial

USDA-ARS?s Scientific Manuscript database

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assign...

The Cooperative Landscape of Multinational Clinical Trials

PubMed Central

Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

2015-01-01

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

Altruism, personal benefit, and anxieties: a phenomenological study of healthy volunteers' experiences in a placebo‐controlled trial of duloxetine

PubMed Central

Kwakye, Isaac N.; Garner, Matthew; Baldwin, David S.; Bamford, Susan; Pinkney, Verity

2016-01-01

Objective The objective of this study was to develop an in‐depth understanding of healthy volunteers' experiences of mental health trials. Methods A qualitative study was nested within a healthy volunteer placebo‐controlled trial of duloxetine, a psychotropic drug used for treating patients with major depression and generalized anxiety disorder. Eight participants were interviewed, and data were analyzed using interpretative phenomenological analysis. Results Interviewees described volunteering for the trial because they were interested in research, wanted the monetary incentive, wanted to help researchers, and wanted to be part of something. On entering the trial, participants considered the possible risks and described feeling anxious, excited, and determined; they had some clear expectations and some loosely held hopes about what would happen. During the trial, participants were curious about whether they were taking duloxetine or placebo, self‐monitored their bodies' reactions, and guessed which treatment they received. On being un‐blinded to treatment allocation after completing the trial, some participants' guesses were confirmed, but others were surprised, and a few were disappointed. Conclusions Small changes to advertising/consent materials to reflect volunteers' motivations could improve recruitment rates to similar trials; “active” placebos might be particularly useful for maintaining blinding in healthy volunteer trials; and sensitive procedures are needed for un‐blinding participants to treatment allocation. © 2016 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd. PMID:27378326

Validation of Placebo in a Manual Therapy Randomized Controlled Trial

PubMed Central

Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

2015-01-01

At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID:26145718

Stepped Care to Optimize Pain care Effectiveness (SCOPE) trial study design and sample characteristics.

PubMed

Kroenke, Kurt; Krebs, Erin; Wu, Jingwei; Bair, Matthew J; Damush, Teresa; Chumbler, Neale; York, Tish; Weitlauf, Sharon; McCalley, Stephanie; Evans, Erica; Barnd, Jeffrey; Yu, Zhangsheng

2013-03-01

Pain is the most common physical symptom in primary care, accounting for an enormous burden in terms of patient suffering, quality of life, work and social disability, and health care and societal costs. Although collaborative care interventions are well-established for conditions such as depression, fewer systems-based interventions have been tested for chronic pain. This paper describes the study design and baseline characteristics of the enrolled sample for the Stepped Care to Optimize Pain care Effectiveness (SCOPE) study, a randomized clinical effectiveness trial conducted in five primary care clinics. SCOPE has enrolled 250 primary care veterans with persistent (3 months or longer) musculoskeletal pain of moderate severity and randomized them to either the stepped care intervention or usual care control group. Using a telemedicine collaborative care approach, the intervention couples automated symptom monitoring with a telephone-based, nurse care manager/physician pain specialist team to treat pain. The goal is to optimize analgesic management using a stepped care approach to drug selection, symptom monitoring, dose adjustment, and switching or adding medications. All subjects undergo comprehensive outcome assessments at baseline, 1, 3, 6 and 12 months by interviewers blinded to treatment group. The primary outcome is pain severity/disability, and secondary outcomes include pain beliefs and behaviors, psychological functioning, health-related quality of life and treatment satisfaction. Innovations of SCOPE include optimized analgesic management (including a stepped care approach, opioid risk stratification, and criteria-based medication adjustment), automated monitoring, and centralized care management that can cover multiple primary care practices. Published by Elsevier Inc.

Strategies for Improving Vaccine Delivery: A Cluster-Randomized Trial.

PubMed

Fu, Linda Y; Zook, Kathleen; Gingold, Janet A; Gillespie, Catherine W; Briccetti, Christine; Cora-Bramble, Denice; Joseph, Jill G; Haimowitz, Rachel; Moon, Rachel Y

2016-06-01

New emphasis on and requirements for demonstrating health care quality have increased the need for evidence-based methods to disseminate practice guidelines. With regard to impact on pediatric immunization coverage, we aimed to compare a financial incentive program (pay-for-performance [P4P]) and a virtual quality improvement technical support (QITS) learning collaborative. This single-blinded (to outcomes assessor), cluster-randomized trial was conducted among unaffiliated pediatric practices across the United States from June 2013 to June 2014. Practices received either the P4P or QITS intervention. All practices received a Vaccinator Toolkit. P4P practices participated in a tiered financial incentives program for immunization coverage improvement. QITS practices participated in a virtual learning collaborative. Primary outcome was percentage of all needed vaccines received (PANVR). We also assessed immunization up-to-date (UTD) status. Data were analyzed from 3,147 patient records from 32 practices. Practices in the study arms reported similar QI activities (∼6 to 7 activities). We found no difference in PANVR between P4P and QITS (mean ± SE, 90.7% ± 1.1% vs 86.1% ± 1.3%, P = 0.46). Likewise, there was no difference in odds of being UTD between study arms (adjusted odds ratio 1.02, 95% confidence interval 0.68 to 1.52, P = .93). In within-group analysis, patients in both arms experienced nonsignificant increases in PANVR. Similarly, the change in adjusted odds of UTD over time was modest and nonsignificant for P4P but reached significance in the QITS arm (adjusted odds ratio 1.28, 95% confidence interval 1.02 to 1.60, P = .03). Participation in either a financial incentives program or a virtual learning collaborative led to self-reported improvements in immunization practices but minimal change in objectively measured immunization coverage. Copyright © 2016 by the American Academy of Pediatrics.

What work has to be done to implement collaborative care for depression? Process evaluation of a trial utilizing the Normalization Process Model

PubMed Central

2010-01-01

Background There is a considerable evidence base for 'collaborative care' as a method to improve quality of care for depression, but an acknowledged gap between efficacy and implementation. This study utilises the Normalisation Process Model (NPM) to inform the process of implementation of collaborative care in both a future full-scale trial, and the wider health economy. Methods Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory randomised controlled trial of a collaborative model of care for depression. Results Findings are presented as they relate to the four factors of the NPM (interactional workability, relational integration, skill-set workability, and contextual integration) and a number of necessary tasks are identified. Using the model, it was possible to observe that predictions about necessary work to implement collaborative care that could be made from analysis of the pre-trial data relating to the four different factors of the NPM were indeed borne out in the post-trial data. However, additional insights were gained from the post-trial interview participants who, unlike those interviewed before the trial, had direct experience of a novel intervention. The professional freedom enjoyed by more senior mental health workers may work both for and against normalisation of collaborative care as those who wish to adopt new ways of working have the freedom to change their practice but are not obliged to do so. Conclusions The NPM provides a useful structure for both guiding and analysing the process by which an intervention is optimized for testing in a larger scale trial or for subsequent full-scale implementation. PMID:20181163

The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature.

PubMed

van den Berg, Joyce; Gordon, Bernardus B M; Snijders, Marcus P M L; Vandenbussche, Frank P H A; Coppus, Sjors F P J

2015-12-01

Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation rates between 53% and 87%. Some reports suggest that sequential treatment with mifepristone and misoprostol leads to higher success rates than misoprostol alone. To evaluate the added value of mifepristone to current non-surgical treatment regimens in women with EPF we performed a systematic literature search. Electronic databases were searched: PubMed, Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. Clinical studies, both randomised and non-randomised trials, reporting on the added value of mifepristone to current non-surgical treatment regimens in women with EPF were included. Data of sixteen studies were extracted using a data extraction sheet (based on the Cochrane Consumers and Communication Review Group's data extraction template). The methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. In five randomised and eleven non-randomised trials, success rates of sequential treatment with mifepristone and misoprostol in case of EPF varied between 52% and 95%. Large heterogeneity existed in treatment regimens and comparators between studies. The existing evidence is insufficient to draw firm conclusions about the added value of mifepristone to misoprostol alone. A sufficiently powered randomised, double blinded placebo-controlled trial is urgently required to test whether, in EPF, the sequential combination of mifepristone with misoprostol is superior to misoprostol only. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endorsement of the CONSORT guidelines, trial registration, and the quality of reporting randomised controlled trials in leading nursing journals: A cross-sectional analysis.

PubMed

Jull, Andrew; Aye, Phyu Sin

2015-06-01

To establish the reporting quality of trials published in leading nursing journals and investigate associations between CONSORT Statement or trial registration endorsment and reporting of design elements. The top 15 nursing journals were searched using Medline for randomised controlled trials published in 2012. Journals were categorised as CONSORT and trial registration promoting based on requirements of submitting authors or the journal's webpage as at January 2014. Data on sequence generation, allocation concealment, follow up, blinding, baseline equivalence and sample size calculation were extracted by one author and independently verified by the second author against source data. Seven journals were CONSORT promoting and three of these journals were also trial registration promoting. 114 citations were identified and 83 were randomised controlled trials. Eighteen trials (21.7%) were registered and those published in trial registration promoting journals were more likely to be registered (RR 2.64 95%CI 1.14-6.09). We assessed 68.7% of trials to be low risk of bias for sequence generation, 20.5% for allocation concealment, 38.6% for blinding, 55.4% for completeness of follow up and 79.5% for baseline equivalence. Trials published in CONSORT promoting journals were more likely to be at low risk of bias for blinding (RR 2.33, 95%CI 1.01-5.34) and completeness of follow up (RR 1.77, 95%CI 1.02-3.10), but journal endorsement of the CONSORT Statement or trial registration otherwise had no significant effect. Trials published in CONSORT and trial registration promoting journals were more likely to have high quality sample size calculations (RR 2.91, 95%CI 1.18-7.19 and RR 1.69, 95%CI 1.08-2.64, respectively). Simple endorsement of the CONSORT Statement and trials registration is insufficient action to encourage improvement of the quality of trial reporting across the most important of trial design elements. Copyright © 2014 Elsevier Ltd. All rights reserved.

COMBAT: Initial experience with a randomized clinical trial of plasma-based resuscitation in the field for traumatic hemorrhagic shock

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Chin, Theresa L; Ghasabyan, Arsen; Chandler, James; Stringham, John; Gonzalez, Eduardo; Moore, Hunter B.; Banerjee, Anirban; Silliman, Christopher C; Sauaia, Angela

2015-01-01

The existing evidence shows great promise for plasma as the first resuscitation fluid in both civilian and military trauma. We embarked on the Control of Major Bleeding After Trauma (COMBAT) trial with the support of the Department of Defense, in order to determine if plasma-first resuscitation yields hemostatic and survival benefits. The methodology of the COMBAT study represents not only three years of development work, but the integration of nearly two-decades of technical experience with the design and implementation of other clinical trials and studies. Herein, we describe the key features of the study design, critical personnel and infrastructural elements, and key innovations. We will also briefly outline the systems engineering challenges entailed by this study. COMBAT is a randomized, placebo controlled, semi-blinded prospective Phase IIB clinical trial, conducted in a ground ambulance fleet based at a Level I trauma center, and part of a multicenter collaboration. The primary objective of COMBAT is to determine the efficacy of field resuscitation with plasma first, compared to standard of care (normal saline). To date we have enrolled 30 subjects in the COMBAT study. The ability to achieve intervention with a hemostatic resuscitation agent in the closest possible temporal proximity to injury is critical and represents an opportunity to forestall the evolution of the “bloody vicious cycle”. Thus, the COMBAT model for deploying plasma in first response units should serve as a model for RCTs of other hemostatic resuscitative agents. PMID:25784527

Alabama Institute for Deaf and Blind Biodiesel Project Green

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

Edmiston, Jessica L

2012-09-28

Through extensive collaboration, Alabama Institute for Deaf and Blind (AIDB) is Alabama's first educational entity to initiate a biodiesel public education, student training and production program, Project Green. With state and national replication potential, Project Green benefits local businesses and city infrastructures within a 120-mile radius; provides alternative education to Alabama school systems and to schools for the deaf and blind in Appalachian States; trains students with sensory and/or multiple disabilities in the acquisition and production of biodiesel; and educates the external public on alternative fuels benefits.

The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Meidahl Petersen, Kasper; Eplov, Kasper; Kjær Nielsen, Torben; Jimenez-Solem, Espen; Petersen, Morten; Broedbaek, Kasper; Daugaard Popik, Sara; Kallehave Hansen, Lina; Enghusen Poulsen, Henrik; Trærup Andersen, Jon

2016-01-01

Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency at baseline. Within the trimethoprim group, serum folate was significantly decreased (P = 0.018) after the trial. We found a mean decrease in serum folate among trimethoprim exposed of 1.95 nmol/L, compared with a 0.21 nmol/L mean increase in the placebo group (P = 0.040). The proportion of folate-deficient participants increased significantly within the trimethoprim group (P = 0.034). No serious adverse events were observed. In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.

A Double Blind Trial of Divalproex Sodium for Affective Liability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2014-10-01

approved it in 1995 for this indication. Also, it is used in conjunction with lithium or carbamazepine to prevent recurrent manic or depressive...TITLE: A Double Blind Trial of Divalproex Sodium for Affective L ability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL...NUMBER Liability and Alcohol Use Following Traumatic Brain Injury 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2009-10-01

SUBJECT TERMS Traumatic Brain Injury, Alcohol Use , Mood , Mood Stabilization 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT 18...1995 for this indication. Also, it is used in conjunction with lithium or carbamazepine to prevent recurrent manic or depressive episodes during long...0652 TITLE: A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

Quality of randomized controlled trials published in the International Urogynecology Journal 2007-2016.

PubMed

Kim, Kyu Shik; Chung, Jae Hoon; Jo, Jung Ki; Kim, Jae Heon; Kim, Seungjun; Cho, Jeoung Man; Cho, Hee Ju; Choi, Hong Yong; Lee, Seung Wook

2018-07-01

Randomized controlled trials (RCTs) provide the best quality clinical evidence. The aim of this study was to assess the quality of RCTs published by the International Urogynecology Journal (IUJ) in 2007-2016. RCTs in original articles were extracted from PubMed and IUJ homepage. Change in RCT quality over time was assessed with Jadad and van Tulder scales and Cochrane Collaboration's risk of bias tool (CCRBT). Jadad scores of 3-5 or van Tulder scores of >5 indicated high-quality RCTs. The effect on RCT quality of including funding source and institutional review board (IRB) approval statements and describing the intervention was assessed. In addition, changes in RCT topics over time were assessed. Annual RCT frequencies did not change significantly (6.7-15.7%): 36.1% and 25.7% described blinding and allocation concealment, respectively. Both tended to increase between 2013 and 2016, particularly 2013 and 2014. Funding statement inclusion (39.1% overall) and intervention description (78.2% overall) tended to increase steadily. IRB statement inclusion (60.4% overall) increased significantly (p < 0.01). Jadad scores and van Tulder rose significantly until 2014 (p < 0.01). Frequencies of high-quality RCTs tended to rise. CCRBT indicated that RCTs with a low risk of bias tended to increase until 2014. However, from 2015, Jadad scores, van Tulder, and CCRBT the low risk tended to decreased. RCTs with funding and IRB approval statements had higher Jadad and van Tulder scores than unfunded RCTs (p < 0.01 and p < 0.01, respectively). Intervention description did not associate with better quality. RCT quality improved over time, but a dip in quality was observed in 2015-2016 because of decreased blinding and allocation concealment.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.

PubMed

McPherson, Ruth; Frohlich, Jiri; Fodor, George; Genest, Jacques; Canadian Cardiovascular Society

2006-09-01

Since the last publication of the recommendations for the management and treatment of dyslipidemia, new clinical trial data have emerged that support a more vigorous approach to lipid lowering in specific patient groups. The decision was made to update the lipid guidelines in collaboration with the Canadian Cardiovascular Society. A systematic electronic search of medical literature for original research consisting of blinded, randomized controlled trials was performed. Meta-analyses of studies of the efficacy and safety of lipid-lowering therapies, and of the predictive value of established and emerging risk factors were also reviewed. All recommendations are evidence-based, and have been reviewed in detail by primary and secondary review panels. Major changes include a lower low-density lipoprotein cholesterol (LDL-C) treatment target (lower than 2.0 mmol/L) for high-risk patients, a slightly higher intervention point for the initiation of drug therapy in most low-risk individuals (LDL-C of 5.0 mmol/L or a total cholesterol to high-density lipoprotein cholesterol ratio of 6.0) and recommendations regarding additional investigations of potential use in the further evaluation of coronary artery disease risk in subjects in the moderate-risk category.

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors

PubMed Central

2012-01-01

Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making. PMID:23151403

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

PubMed

Landolfi, R; Marchioli, R

1997-01-01

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

Resolving controversies in hip fracture care: the need for large collaborative trials in hip fractures.

PubMed

Bhandari, Mohit; Sprague, Sheila; Schemitsch, Emil H

2009-07-01

Hip fractures are a significant cause of morbidity and mortality worldwide and the burden of disability associated with hip fractures globally vindicate the need for high-quality research to advance the care of patients with hip fractures. Historically, large, multi-centre randomized controlled trials have been rare in the orthopaedic trauma literature. Similar to other medical specialties, orthopaedic research is currently undergoing a paradigm shift from single centre initiatives to larger collaborative groups. This is evident with the establishment of several collaborative groups in Canada, in the United States, and in Europe, which has proven that multi-centre trials can be extremely successful in orthopaedic trauma research.Despite ever increasing literature on the topic of his fractures, the optimal treatment of hip fractures remains unknown and controversial. To resolve this controversy large multi-national collaborative randomized controlled trials are required. In 2005, the International Hip Fracture Research Collaborative was officially established following funding from the Canadian Institute of Health Research International Opportunity Program with the mandate of resolving controversies in hip fracture management. This manuscript will describe the need, the information, the organization, and the accomplishments to date of the International Hip Fracture Research Collaborative.

An international collaboration to standardize HIV-2 viral load assays: results from the 2009 ACHI(E)V(2E) quality control study.

PubMed

Damond, F; Benard, A; Balotta, Claudia; Böni, Jürg; Cotten, Matthew; Duque, Vitor; Ferns, Bridget; Garson, Jeremy; Gomes, Perpetua; Gonçalves, Fátima; Gottlieb, Geoffrey; Kupfer, Bernd; Ruelle, Jean; Rodes, Berta; Soriano, Vicente; Wainberg, Mark; Taieb, Audrey; Matheron, Sophie; Chene, Genevieve; Brun-Vezinet, Francoise

2011-10-01

Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHI(E)V(2E) study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log(10) copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log(10) copies/ml and 3.7 log(10) copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed.

An International Collaboration To Standardize HIV-2 Viral Load Assays: Results from the 2009 ACHIEV2E Quality Control Study▿

PubMed Central

Damond, F.; Benard, A.; Balotta, Claudia; Böni, Jürg; Cotten, Matthew; Duque, Vitor; Ferns, Bridget; Garson, Jeremy; Gomes, Perpetua; Gonçalves, Fátima; Gottlieb, Geoffrey; Kupfer, Bernd; Ruelle, Jean; Rodes, Berta; Soriano, Vicente; Wainberg, Mark; Taieb, Audrey; Matheron, Sophie; Chene, Genevieve; Brun-Vezinet, Francoise

2011-01-01

Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHIEV2E study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log10 copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log10 copies/ml and 3.7 log10 copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed. PMID:21813718

Computer-based cognitive training for ADHD: a review of current evidence.

PubMed

Sonuga-Barke, Edmund; Brandeis, Daniel; Holtmann, Martin; Cortese, Samuele

2014-10-01

There has been an increasing interest in and the use of computer-based cognitive training as a treatment of attention-deficit/hyperactivity disorder (ADHD). The authors' review of current evidence, based partly on a stringent meta-analysis of 6 randomized controlled trials (RCTs) published in 2013, and an overview of 8 recently published RCTs highlights the inconsistency of findings between trials and across blinded and nonblinded ADHD measures within trials. Based on this, they conclude that more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

A randomized double-blind trial of two low dose combined oral contraceptives.

PubMed

Bounds, W; Vessey, M; Wiggins, P

1979-04-01

Fifty-five women using Loestrin-20 (20 microgram ethinyl oestradiol and 1 mg norethisterone acetate) as an oral contraceptive have been compared with a like number using Microgynon-30 (30 microgram ethinyl oestradiol and 150 microgram levonorgestrel) in a randomized, double-blind trial. Despite the small sample size, the main finding in the trial is clear-cut; Loestrin-20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon-30. Although there is also a suggestion that Loestrin-20 may be less effective than Microgynon-30, the difference in the accidental pregnancy rates is not statistically significant.

Methodology Series Module 4: Clinical Trials.

PubMed

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

Methodology Series Module 4: Clinical Trials

PubMed Central

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Sahraian, Ali; Jahromi, Leila Razeghian; Ghanizadeh, Ahmad; Mowla, Arash

2017-04-01

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Classroom Guitar and Students with Visual Impairments: A Positive Approach to Music Learning and Artistry

ERIC Educational Resources Information Center

Coleman, Jeremy M.

2016-01-01

In 2011, a collaborative effort began between the Texas School for the Blind and Visually Impaired (TSBVI) and Austin Classical Guitar (ACG), a local 501(c) nonprofit music organization. The idea behind this collaboration was to start a small guitar program that would provide TSBVI students with quality classroom guitar instruction. At that time,…

Bridging the Gap between Physical Therapy and Orientation and Mobility in Schools: Using a Collaborative Team Approach for Students with Visual Impairments

ERIC Educational Resources Information Center

Szabo, Joanne; Panikkar, Rajiv K.

2017-01-01

This article explores transdisciplinary collaboration and role-release strategies that would allow physical therapists and orientation and mobility (O&M) specialists to more effectively support students with visual impairments (that is, those who are blind or have low vision) and additional disabilities with their expanded core curriculum…

[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies].

PubMed

Ammar, G; Naja, W J; Pelissolo, A

2015-06-01

Anxiety disorders are widespread psychiatric conditions with significant social and professional disability, poor quality of life, an increased risk of suicide, and frequent attendance of medical services. Serotonin reuptake inhibitors (SRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) have demonstrated a rather robust efficacy for the treatment of most of anxiety disorders. Nevertheless a substantial number of patients are resistant or still suffer from residual symptoms despite this first line treatment. The objective of our paper is to review relevant studies for the pharmacologic management of anxiety disorders resistant to the first line treatment. For this purpose, we conducted a pubmed/medline search for double-blind placebo-controlled trials of treatment-resistant anxiety disorders. An adequate trial for a SRI in the treatment of obsessive-compulsive disorder (OCD) should continue for at least 12 weeks. Special considerations of the comorbidities and symptom profile could help in the choice of an appropriate pharmacotherapy. Several trials have highlighted the efficacy of antipsychotics as an add-on to SRI in treatment-resistant OCD such as haloperidol more so when comorbid with a tic disorder, or risperidone that can reduce OCD as well as depressive symptoms. Aripiprazole has been shown efficacious in two placebo-controlled double-blind trials, while the efficacy of quetiapine and olanzapine remains controversial. Other trials showed some efficacy of anticonvulsants (lamotrigine, topiramate), pindolol, memantin and N-acetylcystein as an adjunctive treatment to SRI for resistant OCD. Few trials have investigated selective serotonin reuptake inhibitors (SSRI) or SNRI resistant generalized anxiety disorder showing a failure of adjunctive therapy with olanzapine, quetiapine, ziprasidone and risperidone. These studies were underpowered and very limited in number. Adjunctive risperidone for resistant post-traumatic stress disorder (PTSD) showed benefit in some but not all trials. Olanzapine was beneficial for the reduction of the CAPS score in addition to the improvement of sleep disturbances. Furthermore, prazosin was efficacious by reducing PTSD symptoms, sleep disturbances, nightmares, and psychological distress. One double-blind placebo-controlled study was conducted to investigate treatment-resistant social phobia showing no benefit of pindolol add-on paroxetine. Our results demonstrate that the pharmacological management of treatment-resistant anxiety disorders is not sufficiently investigated in double-blind placebo-controlled trials, despite a growing evidence in favor of antipsychotics and some other pharmacological agents in resistant OCD and, to a lesser extent, PTSD. Hence, there is a crucial need for larger double-blind placebo-controlled trials for resistant anxiety disorders. Finally, being out of the scope of our review, we omitted studies of non-pharmacologic therapies. Copyright © 2014. Published by Elsevier Masson SAS.

Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial.

PubMed

Nieminen, Heta; Syrjänen, Ritva K; Puumalainen, Taneli; Sirén, Päivi; Palmu, Arto A

2015-07-17

The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was a nationwide cluster-randomised double-blind trial designed to demonstrate the effectiveness of pneumococcal conjugate vaccine in vaccinated children and indirect effects in unvaccinated populations. Together with the parallel carriage/AOM trial, over 47,000 children were enrolled, 52% of the initial target. We conducted a questionnaire study to find out which factors affected parents' decision on their child's study participation. A questionnaire designed to evaluate parents' attitudes to vaccine trial participation in general and the FinIP trial in particular was mailed after the trial enrolment period had ended to parents of randomly selected children: 1484 who participated in the trial and 1485 who did not participate. Altogether 1438 parents (48%) responded to the questionnaire. The response rate was higher among FinIP participants (65%, 965/1484) than among FinIP non-participants (32%, 473/1485). The two most important reasons for giving consent to the FinIP trial were the potential benefit of immunisation against pneumococcal diseases (75% of consenters) and the promotion of the common good and public health (11%). The reasons reported as most important for declining consent were suspicions of vaccine safety (36%) and the double-blind trial design (12%). Up to 65% of the non-consenters declared that drug and vaccine trials should not be conducted in children at all. The expected health benefit for the child was by far the most important reason for consenting to the vaccine trial. Safety concern was the main reason for decline. Importance and necessity of clinical drug and vaccine trials among children and the rationale of the blinded studies should be thoroughly explained to the public. This may increase participation in future vaccine trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Current hydration guidelines are erroneous: dehydration does not impair exercise performance in the heat.

PubMed

Wall, Bradley A; Watson, Greig; Peiffer, Jeremiah J; Abbiss, Chris R; Siegel, Rodney; Laursen, Paul B

2015-08-01

Laboratory studies that support the hydration guidelines of leading governing bodies have shown that dehydration to only -2% of body mass can lead to increase in body temperature and heart rate during exercise, and decrease in performance. These studies, however, have been conducted in relatively windless environments (ie, wind speed <12.9 km/h), without participants being blinded to their hydration status. To investigate the effect of blinded hydration status on cycling time-trial performance in the heat with ecologically valid facing wind speed conditions. During three experimental trials, 10 cyclists were dehydrated to -3% body mass by performing 2 h of submaximal exercise (walking and cycling) in the heat, before being reinfused with saline to replace 100%, 33% or 0% of fluid losses, leaving them 0%, -2% or -3% hypohydrated, respectively. Participants then completed a 25 km time trial in the heat (33°C, 40% relative humidity; wind speed 32 km/h) during which their starting hydration status was maintained by infusing saline at a rate equal to their sweat rate. The treatment was participant-blinded and the order was randomised. Completion time, power output, heart rate, rectal temperature and perceptual variables were measured. While rectal temperature was higher beyond 17 km of the time trial in the -3% vs 0% conditions (38.9±0.3°C vs 38.6±0.3°C; p<0.05), no other differences between trials were shown. When well-trained cyclists performed a 25 km cycling time trial under ecologically valid conditions and were blinded to their hydration status, performance, physiological and perceptual variables were not different between trials. These data do not support the residing basis behind many of the current hydration guidelines. 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.

Manipulation Detection and Preference Alterations in a Choice Blindness Paradigm

PubMed Central

Taya, Fumihiko; Gupta, Swati; Farber, Ilya; Mullette-Gillman, O'Dhaniel A.

2014-01-01

Objectives It is commonly believed that individuals make choices based upon their preferences and have access to the reasons for their choices. Recent studies in several areas suggest that this is not always the case. In choice blindness paradigms, two-alternative forced-choice in which chosen-options are later replaced by the unselected option, individuals often fail to notice replacement of their chosen option, confabulate explanations for why they chose the unselected option, and even show increased preferences for the unselected-but-replaced options immediately after choice (seconds). Although choice blindness has been replicated across a variety of domains, there are numerous outstanding questions. Firstly, we sought to investigate how individual- or trial-factors modulated detection of the manipulations. Secondly, we examined the nature and temporal duration (minutes vs. days) of the preference alterations induced by these manipulations. Methods Participants performed a computerized choice blindness task, selecting the more attractive face between presented pairs of female faces, and providing a typewritten explanation for their choice on half of the trials. Chosen-face cue manipulations were produced on a subset of trials by presenting the unselected face during the choice explanation as if it had been selected. Following all choice trials, participants rated the attractiveness of each face individually, and rated the similarity of each face pair. After approximately two weeks, participants re-rated the attractiveness of each individual face online. Results Participants detected manipulations on only a small proportion of trials, with detections by fewer than half of participants. Detection rates increased with the number of prior detections, and detection rates subsequent to first detection were modulated by the choice certainty. We show clear short-term modulation of preferences in both manipulated and non-manipulated explanation trials compared to choice-only trials (with opposite directions of effect). Preferences were altered in the direction that subjects were led to believe they selected. PMID:25247886

The challenges of control groups, placebos and blinding in clinical trials of dietary interventions.

PubMed

Staudacher, Heidi M; Irving, Peter M; Lomer, Miranda C E; Whelan, Kevin

2017-08-01

High-quality placebo-controlled evidence for food, nutrient or dietary advice interventions is vital for verifying the role of diet in optimising health or for the management of disease. This could be argued to be especially important where the benefits of dietary intervention are coupled with potential risks such as compromising nutrient intake, particularly in the case of exclusion diets. The objective of the present paper is to explore the challenges associated with clinical trials in dietary research, review the types of controls used and present the advantages and disadvantages of each, including issues regarding placebos and blinding. Placebo-controlled trials in nutrient interventions are relatively straightforward, as in general placebos can be easily produced. However, the challenges associated with conducting placebo-controlled food interventions and dietary advice interventions are protean, and this has led to a paucity of placebo-controlled food and dietary advice trials compared with drug trials. This review appraises the types of controls used in dietary intervention trials and provides recommendations and nine essential criteria for the design and development of sham diets for use in studies evaluating the effect of dietary advice, along with practical guidance regarding their evaluation. The rationale for these criteria predominantly relate to avoiding altering the outcome of interest in those delivered the sham intervention in these types of studies, while not compromising blinding.

The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress

PubMed Central

Antic, Nick A.; Heeley, Emma; Anderson, Craig S.; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R. Doug

2015-01-01

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical Trials Registration Number: NCT00738179. Australia New Zealand Clinical Trials Registry Number: ACTRN12608000409370. Citation: Antic NA, Heeley E, Anderson CS, Luo Y, Wang J, Neal B, Grunstein R, Barbe F, Lorenzi-Filho G, Huang S, Redline S, Zhong N, McEvoy RD. The sleep apnea cardiovascular endpoints (SAVE) trial: rationale, ethics, design, and progress. SLEEP 2015;38(8):1247–1257. PMID:25669180

Management of oral lesions in HIV-positive patients.

PubMed

Baccaglini, Lorena; Atkinson, Jane C; Patton, Lauren L; Glick, Michael; Ficarra, Giuseppe; Peterson, Douglas E

2007-03-01

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.

PubMed

Berk, Michael; Dean, Olivia M; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Moss, Kirsteen; Allwang, Christine; Schapkaitz, Ian; Cobb, Heidi; Bush, Ashley I; Dodd, Seetal; Malhi, Gin S

2012-08-14

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

acutely manic bipolar patients, and the FDA approved it in 1995 for this indication. Also, it is used in conjunction with lithium or carbamazepine to...0652 TITLE: A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury...and Alcohol Use Following Traumatic Brain Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-2-0652 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury

DTIC Science & Technology

2010-10-01

comparable to lithium in treating acutely manic bipolar patients, and the FDA approved it in 1995 for this indication. Also, it is used in conjunction with...A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury PRINCIPAL INVESTIGATOR...Lability and Alcohol Use Following Traumatic Brain Injury 5b. GRANT NUMBER W81XWH-08-2-0652 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Fluid Lavage of Open Wounds (FLOW): A Multicenter, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures

DTIC Science & Technology

2013-10-01

Multicenter, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures PRINCIPAL...Solutions and Pressures in Patients with Open Fractures 5b. GRANT NUMBER W81XWH-12-1-0530 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kyle J. Jeray...important initial step in preventing infection in open fractures . However, there is little clinical evidence as to the best irrigation methods and additives

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

PubMed Central

2012-01-01

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493). PMID:22891797

Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

PubMed Central

2014-01-01

Background The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. Methods/Design The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. Discussion Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. Trial registration ClinicalTrials.gov: NCT01119014 PMID:25015535

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

PubMed

Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

Differential Globalization of Industry- and Non-Industry-Sponsored Clinical Trials.

PubMed

Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

2015-01-01

Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry-sponsored clinical trials and its evolution over time. We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry-sponsored international trials. 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry-sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry-sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry-sponsored trials (from 42.4% to 37.2%). Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry-sponsored clinical research. Only 3% of academic trials but 30% of industry trials are international. The latter appeared to be conducted in preferentially selected countries.

Differential Globalization of Industry- and Non-Industry–Sponsored Clinical Trials

PubMed Central

Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

2015-01-01

Background Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry–sponsored clinical trials and its evolution over time. Methods We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry–sponsored international trials. Results 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry–sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry–sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry–sponsored trials (from 42.4% to 37.2%). Conclusions Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry–sponsored clinical research. Only 3% of academic trials but 30% of industry trials are international. The latter appeared to be conducted in preferentially selected countries. PMID:26658791

Wet cupping therapy for treatment of herpes zoster: a systematic review of randomized controlled trials.

PubMed

Cao, Huijuan; Zhu, Chenjun; Liu, Jianping

2010-01-01

Wet cupping is a traditional Chinese medicine therapy commonly used in treating herpes zoster in China, and clinical studies have shown that wet cupping may have beneficial effect on herpes zoster compared with Western medication. We included randomized controlled trials (RCTs) on wet cupping for herpes zoster. We searched PubMed, the Cochrane Library (Issue 3, 2008), China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journals Fulltext Database VIP, and Wan Fang Database. All searches ended in February 2009. Two authors extracted data and assessed the trials' quality independently. RevMan 5.0.18 software (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). Eight RCTs involving 651 patients were included, and the methodological quality of trials was generally fair in terms of randomization, blinding, and intention-to-treat analysis. Meta-analyses showed wet cupping was superior to medication in the number of cured patients (RR 2.49, 95% CI 1.91 to 3.24, P < .00001), the number of patients with improved symptoms (RR 1.15, 95% CI 1.05 to 1.26, P = .003), and reducing the incidence rate of postherpetic neuralgia (RR 0.06, 95% CI 0.02 to 0.25, P = .0001). Wet cupping plus medication was significantly better than medication alone on number of cured patients (RR 1.93, 95% CI 1.23 to 3.04, P = .005) but demonstrated no difference in symptom improvement (RR 1.00, 95% CI 0.92 to 1.08, P = .98). There were no serious adverse effects related to wet cupping therapy in the included trials. Wet cupping appears to be effective in the treatment of herpes zoster. However, further large, rigorously designed

Randomised controlled trial of the clinical and cost effectiveness of a specialist team for managing refractory unipolar depressive disorder.

PubMed

Morriss, Richard; Marttunnen, Sarah; Garland, Anne; Nixon, Neil; McDonald, Ruth; Sweeney, Tim; Flambert, Heather; Fox, Richard; Kaylor-Hughes, Catherine; James, Marilyn; Yang, Min

2010-11-29

Around 40 per cent of patients with unipolar depressive disorder who are treated in secondary care mental health services do not respond to first or second line treatments for depression. Such patients have 20 times the suicide rate of the general population and treatment response becomes harder to achieve and sustain the longer they remain depressed. Despite this there are no randomised controlled trials of community based service delivery interventions delivering both algorithm based pharmacotherapy and psychotherapy for patients with chronic depressive disorder in secondary care mental health services who remain moderately or severely depressed after six months treatment. Without such trials evidence based guidelines on services for such patients cannot be derived. Single blind individually randomised controlled trial of a specialist depression disorder team (psychiatrist and psychotherapist jointly assessing and providing algorithm based drug and psychological treatment) versus usual secondary care treatment. We will recruit 174 patients with unipolar depressive disorder in secondary mental health services with a Hamilton Depression Rating Scale (HDRS) score ≥ 16 and global assessment of function (GAF) ≤ 60 after ≥ 6 months treatment. The primary outcome measures will be the HDRS and GAF supplemented by economic analysis including the EQ5 D and analysis of barriers to care, implementation and the process of care. Audits to benchmark both treatment arms against national standards of care will aid the interpretation of the results of the study. This trial will be the first to assess the effectiveness and implementation of a community based specialist depression disorder team. The study has been specially designed as part of the CLAHRC Nottinghamshire, Derbyshire and Lincolnshire joint collaboration between university, health and social care organisations to provide information of direct relevance to decisions on commissioning, service provision and implementation.

Involving service users in trials: developing a standard operating procedure

PubMed Central

2013-01-01

Background Many funding bodies require researchers to actively involve service users in research to improve relevance, accountability and quality. Current guidance to researchers mainly discusses general principles. Formal guidance about how to involve service users operationally in the conduct of trials is lacking. We aimed to develop a standard operating procedure (SOP) to support researchers to involve service users in trials and rigorous studies. Methods Researchers with experience of involving service users and service users who were contributing to trials collaborated with the West Wales Organisation for Rigorous Trials in Health, a registered clinical trials unit, to develop the SOP. Drafts were prepared in a Task and Finish Group, reviewed by all co-authors and amendments made. Results We articulated core principles, which defined equality of service users with all other research team members and collaborative processes underpinning the SOP, plus guidance on how to achieve these. We developed a framework for involving service users in research that defined minimum levels of collaboration plus additional consultation and decision-making opportunities. We recommended service users be involved throughout the life of a trial, including planning and development, data collection, analysis and dissemination, and listed tasks for collaboration. We listed people responsible for involving service users in studies and promoting an inclusive culture. We advocate actively involving service users as early as possible in the research process, with a minimum of two on all formal trial groups and committees. We propose that researchers protect at least 1% of their total research budget as a minimum resource to involve service users and allow enough time to facilitate active involvement. Conclusions This SOP provides guidance to researchers to involve service users successfully in developing and conducting clinical trials and creating a culture of actively involving service users in research at all stages. The UK Clinical Research Collaboration should encourage clinical trials units actively to involve service users and research funders should provide sufficient funds and time for this in research grants. PMID:23866730

AACCI Approved Methods Technical Committee Report: Collaborative study on a method for determining the water holding capacity of pulse flours and their protein materials (AACCI Method 56-37.01)

USDA-ARS?s Scientific Manuscript database

A method for determining water holding capacity (WHC) of pulse flours and protein materials has been developed and subjected to an interlaboratory study. Eleven participants analyzed twelve blind duplicates of six different samples in a collaborative study to evaluate the repeatability and reproduci...

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

PubMed

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials

NASA Astrophysics Data System (ADS)

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

PubMed Central

Bennell, Kim; Bowles, Kelly-Ann; Payne, Craig; Cicuttini, Flavia; Osborne, Richard; Harris, Anthony; Hinman, Rana

2007-01-01

Background Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. Methods/Design Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. Trial registration ACTR12605000503628; NCT00415259. PMID:17892539

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

PubMed Central

Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

2015-01-01

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

Characterisation of trials where marketing purposes have been influential in study design: a descriptive study.

PubMed

Barbour, Virginia; Burch, Druin; Godlee, Fiona; Heneghan, Carl; Lehman, Richard; Perera, Rafael; Ross, Joseph S; Schroter, Sara

2016-01-21

Analysis of trial documentation has revealed that some industry-funded trials may be done more for marketing purposes than scientific endeavour. We aimed to define characteristics of drug trials that appear to be influenced by marketing considerations and estimate their prevalence. We examined reports of randomised controlled trials of drugs published in six general medical journals in 2011. Six investigators independently reviewed all publications, characterising them as YES/MAYBE/NO suspected marketing trials, and then met to reach consensus. Blinded researchers then extracted key trial characteristics. We used blinded cluster analysis to determine if key variables could characterise the categories of trials (YES/MAYBE/NO). 41/194 (21 %) trials were categorised as YES, 14 (7 %) as MAYBE, 139 (72 %) as NO. All YES and MAYBE trials were funded by the manufacturer, compared with 37 % of NO trials (p < 0.001). A higher proportion of YES trials had authors or contributors from the manufacturer involved in study design (83 % vs. 19 %), data analysis (85 % vs.15 %) and reporting (81 % vs. 15 %) than NO trials (p < 0.001). There was no significant difference between groups in the median number of participants screened (p = 0.49), but the median number of centres recruiting participants was higher for YES compared with NO trials (171 vs. 13, p < 0.001). YES trials were not more likely to use a surrogate (42 % vs. 30 %; p = 0.38) or composite primary outcome measure (34 % vs. 19 %; p = 0.14) than NO trials. YES trials were often better reported in terms of blinding, safety outcomes and adverse events than NO trials. YES trials more frequently included speculation that might encourage clinicians to use the intervention outside of the study population compared to NO trials (59 % vs.37 %, p = 0.03). Cluster analysis based on study characteristics did not identify a clear variable structure that accurately characterised YES/MAYBE/NO trials. We reached consensus that a fifth of drug trials published in the highest impact general medical journals in 2011 had features that were suggestive of being designed for marketing purposes. Each of the marketing trials appeared to have a unique combination of features reported in the journal publications.

Misoprostol dose-related shivering and pyrexia in the third stage of labour. WHO Collaborative Trial of Misoprostol in the Management of the Third Stage of Labour.

PubMed

Lumbiganon, P; Hofmeyr, J; Gülmezoglu, A M; Pinol, A; Villar, J

1999-04-01

To select the misoprostol dose to be used in a large multicentre randomised trial comparing misoprostol with oxytocin in the routine management of the third stage of labour. Randomised pilot trial, double-blinded with the use of double placebos. Two of the nine hospitals that will participate in the main multicentre trial. The hospitals were located in Johannesburg, South Africa and Khon Kaen, Thailand. Women during second stage of labour about to be delivered vaginally. The trial had three arms: misoprostol 400 microg versus misoprostol 600 microg versus intramuscular oxytocin 10 IU. Each group received an injection and three tablets immediately after the birth of the baby. Shivering and pyrexia rates were the main outcome measures. Data on other side effects and characteristics of the third stage of labour were also collected. Side effects were noted as none, mild, moderate or severe. Both shivering and pyrexia (temperature > 38 degrees C) were most common in the 600 microg misoprostol group (28% and 7.5% for shivering and pyrexia, respectively) compared with 400 microg misoprostol (19% and 2%), and the oxytocin group (12.5% and 3%). The increase in shivering in the misoprostol 600 microg group was due primarily to a higher rate of moderate shivering. None of the women had a temperature > 40 degrees C. There were no increases in severe side effects and other adverse events in the misoprostol 600 microg group. When used in the management of the third stage of labour oral misoprostol is associated with an increase in the rate of moderate shivering and pyrexia which seems to be dose-related. Based on the results of this pilot trial, the Steering Committee has decided to use 600 microg misoprostol in the main trial, comparing it with oxytocin, in order to achieve higher effectiveness.

Blindness enhances auditory obstacle circumvention: Assessing echolocation, sensory substitution, and visual-based navigation

PubMed Central

Scarfe, Amy C.; Moore, Brian C. J.; Pardhan, Shahina

2017-01-01

Performance for an obstacle circumvention task was assessed under conditions of visual, auditory only (using echolocation) and tactile (using a sensory substitution device, SSD) guidance. A Vicon motion capture system was used to measure human movement kinematics objectively. Ten normally sighted participants, 8 blind non-echolocators, and 1 blind expert echolocator navigated around a 0.6 x 2 m obstacle that was varied in position across trials, at the midline of the participant or 25 cm to the right or left. Although visual guidance was the most effective, participants successfully circumvented the obstacle in the majority of trials under auditory or SSD guidance. Using audition, blind non-echolocators navigated more effectively than blindfolded sighted individuals with fewer collisions, lower movement times, fewer velocity corrections and greater obstacle detection ranges. The blind expert echolocator displayed performance similar to or better than that for the other groups using audition, but was comparable to that for the other groups using the SSD. The generally better performance of blind than of sighted participants is consistent with the perceptual enhancement hypothesis that individuals with severe visual deficits develop improved auditory abilities to compensate for visual loss, here shown by faster, more fluid, and more accurate navigation around obstacles using sound. PMID:28407000

Blindness enhances auditory obstacle circumvention: Assessing echolocation, sensory substitution, and visual-based navigation.

PubMed

Kolarik, Andrew J; Scarfe, Amy C; Moore, Brian C J; Pardhan, Shahina

2017-01-01

Performance for an obstacle circumvention task was assessed under conditions of visual, auditory only (using echolocation) and tactile (using a sensory substitution device, SSD) guidance. A Vicon motion capture system was used to measure human movement kinematics objectively. Ten normally sighted participants, 8 blind non-echolocators, and 1 blind expert echolocator navigated around a 0.6 x 2 m obstacle that was varied in position across trials, at the midline of the participant or 25 cm to the right or left. Although visual guidance was the most effective, participants successfully circumvented the obstacle in the majority of trials under auditory or SSD guidance. Using audition, blind non-echolocators navigated more effectively than blindfolded sighted individuals with fewer collisions, lower movement times, fewer velocity corrections and greater obstacle detection ranges. The blind expert echolocator displayed performance similar to or better than that for the other groups using audition, but was comparable to that for the other groups using the SSD. The generally better performance of blind than of sighted participants is consistent with the perceptual enhancement hypothesis that individuals with severe visual deficits develop improved auditory abilities to compensate for visual loss, here shown by faster, more fluid, and more accurate navigation around obstacles using sound.

Zonisamide and renal calculi in patients with epilepsy: how big an issue?

PubMed

Wroe, Stephen

2007-08-01

To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

PubMed

Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

2016-01-01

The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian). Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 10(10) pu, 35 [38%] to 2·5 × 10(10) pu, 35 [38%] to 5 × 10(10) pu, and 11 [12%] to 1 × 10(11) pu) and 20 in the USA (ten [50%] to 1 × 10(10) pu and ten [50%] to 1 × 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 10(10) and two [2%] received 1 × 10(11) pu) and four (20%) of 20 in the USA (all received 1 × 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness. 1 × 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers). Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases. Copyright © 2016 Tapia et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Projecting Event-Based Analysis Dates in Clinical Trials: An Illustration Based on the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration. Projecting analysis dates for the IDEA collaboration.

PubMed

Renfro, Lindsay A; Grothey, Axel M; Paul, James; Floriani, Irene; Bonnetain, Franck; Niedzwiecki, Donna; Yamanaka, Takeharu; Souglakos, Ioannis; Yothers, Greg; Sargent, Daniel J

2014-12-01

Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Real-time projection of the final analysis time during a trial, or the overall analysis time during a trial collaborative such as IDEA, has practical implications for trial feasibility when these projections are translated into additional time and resources required.

Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia.

PubMed

MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G

2014-07-10

Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728). 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.

Quality of life in newly diagnosed glaucoma patients : The Collaborative Initial Glaucoma Treatment Study.

PubMed

Janz, N K; Wren, P A; Lichter, P R; Musch, D C; Gillespie, B W; Guire, K E

2001-05-01

The Collaborative Initial Glaucoma Treatment Study (CIGTS) was designed to determine whether patients with newly diagnosed open-angle glaucoma are better treated initially by medicine or immediate filtering surgery. This paper describes the quality-of-life (QOL) measurement approach, instruments included, and the CIGTS participants' QOL findings at the time of diagnosis. Baseline results from a randomized, controlled clinical trial. Six hundred seven patients from 14 clinical centers were enrolled. Patients randomized to initial medication received a stepped medical regimen (n = 307). Those randomized to initial surgery underwent a trabeculectomy (n = 300). The baseline interview was conducted before treatment initiation. All baseline and posttreatment QOL assessments were conducted by telephone from a centralized interviewing center. The primary outcome measure described in this paper was QOL. The QOL instrument is multidimensional and incorporates both disease-specific and generic measures, including the Visual Activities Questionnaire, Sickness Impact Profile, and a Symptom and Health Problem CHECKLIST: The correlations between QOL measures and clinical outcomes were in the expected direction, but relatively weak. At initial diagnosis, difficulty with bright lights and with light and dark adaptation were the most frequently reported symptoms related to visual function, whereas visual distortion was the most bothersome. Approximately half of the patients reported at least some worry or concern about the possibility of blindness. Within the Visual Activities Questionnaire, higher scores on the Peripheral Vision subscale were associated with more field loss (P < 0.01). In regression analyses controlling for sociodemographics and nonocular comorbidities, increased visual field loss was significantly associated with higher dysfunction among five disease-specific QOL measures (P < 0.05). Newly diagnosed glaucoma patients reported experiencing some visual function symptoms at the time of diagnosis that would not be intuitively expected based on clinical testing. Some discussion about the association between clinical presentation and worry about blindness may reduce unnecessary concern. These results provide the basis for long-term comparisons of the QOL effects of initial medical and surgical treatment for open-angle glaucoma.

Augmentation in the treatment of restless legs syndrome with transdermal rotigotine.

PubMed

Beneš, Heike; García-Borreguero, Diego; Ferini-Strambi, Luigi; Schollmayer, Erwin; Fichtner, Andreas; Kohnen, Ralf

2012-06-01

To assess the risk of augmentation under treatment with the transdermally delivered dopamine agonist rotigotine for restless legs syndrome (RLS). Experts in RLS augmentation retrospectively reviewed data from two double-blind, placebo-controlled 6-month trials (745 rotigotine and 214 placebo subjects, NCT00136045 and NCT00135993) and from two open-label 1-year trials (620 rotigotine subjects, NCT00498108 and NCT00263068). All study visits were systematically evaluated applying the Max Planck Institute (MPI) criteria for the diagnosis of both augmentation and clinically relevant augmentation. MPI criteria for augmentation were met on at least one visit by 8.2% of all subjects in the double-blind trials with 12 subjects meeting the criteria for clinically relevant augmentation: 11 under rotigotine (1.5%) and one under placebo treatment. In the open-label trials, 9.7% of all subjects met the MPI criteria for augmentation and 2.9% met the criteria for clinically relevant augmentation. None of the patients treated with rotigotine for up to 1.5 years (double-blind plus open-label trial) discontinued prematurely owing to augmentation. Neither could dose-dependency or a time pattern for clinically relevant augmentation episodes be detected. Our analyses suggest that the risk for clinically relevant augmentation for the duration of up to 18 months of rotigotine treatment is low. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of a Collaborative Care Intervention vs Usual Care on Health Status of Patients With Chronic Heart Failure: The CASA Randomized Clinical Trial.

PubMed

Bekelman, David B; Allen, Larry A; McBryde, Connor F; Hattler, Brack; Fairclough, Diane L; Havranek, Edward P; Turvey, Carolyn; Meek, Paula M

2018-04-01

Many patients with chronic heart failure experience reduced health status despite receiving conventional therapy. To determine whether a symptom and psychosocial collaborative care intervention improves heart failure-specific health status, depression, and symptom burden in patients with heart failure. A single-blind, 2-arm, multisite randomized clinical trial was conducted at Veterans Affairs, academic, and safety-net health systems in Colorado among outpatients with symptomatic heart failure and reduced health status recruited between August 2012 and April 2015. Data from all participants were included regardless of level of participation, using an intent-to-treat approach. Patients were randomized 1:1 to receive the Collaborative Care to Alleviate Symptoms and Adjust to Illness (CASA) intervention or usual care. The CASA intervention included collaborative symptom care provided by a nurse and psychosocial care provided by a social worker, both of whom worked with the patients' primary care clinicians and were supervised by a study primary care clinician, cardiologist, and palliative care physician. The primary outcome was patient-reported heart failure-specific health status, measured by difference in change scores on the Kansas City Cardiomyopathy Questionnaire (range, 0-100) at 6 months. Secondary outcomes included depression (measured by the 9-item Patient Health Questionnaire), anxiety (measured by the 7-item Generalized Anxiety Disorder Questionnaire), overall symptom distress (measured by the General Symptom Distress Scale), specific symptoms (pain, fatigue, and shortness of breath), number of hospitalizations, and mortality. Of 314 patients randomized (157 to intervention arm and 157 to control arm), there were 67 women and 247 men, mean (SD) age was 65.5 (11.4) years, and 178 (56.7%) had reduced ejection fraction. At 6 months, the mean Kansas City Cardiomyopathy Questionnaire score improved 5.5 points in the intervention arm and 2.9 points in the control arm (difference, 2.6; 95% CI, -1.3 to 6.6; P = .19). Among secondary outcomes, depressive symptoms and fatigue improved at 6 months with CASA (effect size of -0.29 [95% CI, -0.53 to -0.04] for depressive symptoms and -0.30 [95% CI, -0.55 to -0.06] for fatigue; P = .02 for both). There were no significant changes in overall symptom distress, pain, shortness of breath, or number of hospitalizations. Mortality at 12 months was similar in both arms (10 patients died receiving CASA, and 13 patients died receiving usual care; P = .52). This multisite randomized clinical trial of the CASA intervention did not demonstrate improved heart failure-specific health status. Secondary outcomes of depression and fatigue, both difficult symptoms to treat in heart failure, improved. clinicaltrials.gov Identifier: NCT01739686.

Safety and Efficacy of the BrainPort V100 Device in Individuals Blinded by Traumatic Injury

DTIC Science & Technology

2017-12-01

study was to investigate the impact of the BrainPort V200 on real-world functional task performance in persons who are profoundly blind (no better than...16 6. Products 16 7. Participants & Other Collaborating Organizations 16 8. Special Reporting Requirements 18 9. Appendix...environment. The purpose of this study was to evaluate the safety and effectiveness of the BrainPort V200 in individuals who have been medically

Long-term results from an epiretinal prosthesis to restore sight to the blind

PubMed Central

Ho, Allen C.; Humayun, Mark S.; Dorn, Jessy D.; da Cruz, Lyndon; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Brown, Gary C.; Haller, Julia A.; Regillo, Carl D.; Del Priore, Lucian V.; Arditi, Aries; Geruschat, Duane R.; Greenberg, Robert J.

2015-01-01

Purpose Retinitis Pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. A rare disease, it affects about 100,000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in restoring some visual function to subjects completely blind from RP. Herein, we report clinical trial results at 1 and 3 years post-implant. Design The study is a multicenter, single-arm, prospective clinical trial. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Subjects served as their own controls – i.e., implanted eye vs. fellow eye, and System ON vs. System OFF (native residual vision). Methods The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Results Twenty-nine out of 30 subjects remained implanted with functioning Argus II Systems at 3 years post-implant. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the System ON than OFF on all visual function tests and functional vision assessments. Conclusions The three-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the FDA and a CE Mark in Europe. The Argus II System is the first and only retinal implant to have both approvals. PMID:26162233

Blindness prevention programmes: past, present, and future.

PubMed Central

Resnikoff, S.; Pararajasegaram, R.

2001-01-01

Blindness and visual impairment have far-reaching implications for society, the more so when it is realized that 80% of visual disability is avoidable. The marked increase in the size of the elderly population, with their greater propensity for visually disabling conditions, presents a further challenge in this respect. However, if available knowledge and skills were made accessible to those communities in greatest need, much of this needless blindness could be alleviated. Since its inception over 50 years ago, and beginning with trachoma control, WHO has spearheaded efforts to assist Member States to meet the challenge of needless blindness. Since the establishment of the WHO Programme for the Prevention of Blindness in 1978, vast strides have been made through various forms of technical support to establish national prevention of blindness programmes. A more recent initiative, "The Global Initiative for the Elimination of Avoidable Blindness" (referred to as "VISION 2020--The Right to Sight"), launched in 1999, is a collaborative effort between WHO and a number of international nongovernmental organizations and other interested partners. This effort is poised to take the steps necessary to achieve the goal of eliminating avoidable blindness worldwide by the year 2020. PMID:11285666

An Assessment of the Risk of Bias in Randomized Controlled Trial Reports Published in Prosthodontic and Implant Dentistry Journals.

PubMed

Papageorgiou, Spyridon N; Kloukos, Dimitrios; Petridis, Haralampos; Pandis, Nikolaos

2015-01-01

The objective of this study was to assess the risk of bias of randomized controlled trials (RCTs) published in prosthodontic and implant dentistry journals. The last 30 issues of 9 journals in the field of prosthodontic and implant dentistry (Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, Implant Dentistry, International Journal of Oral & Maxillofacial Implants, International Journal of Periodontics and Restorative Dentistry, International Journal of Prosthodontics, Journal of Dentistry, Journal of Oral Rehabilitation, and Journal of Prosthetic Dentistry) were hand-searched for RCTs. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool and analyzed descriptively. From the 3,667 articles screened, a total of 147 RCTs were identified and included. The number of published RCTs increased with time. The overall distribution of a high risk of bias assessment varied across the domains of the Cochrane risk of bias tool: 8% for random sequence generation, 18% for allocation concealment, 41% for masking, 47% for blinding of outcome assessment, 7% for incomplete outcome data, 12% for selective reporting, and 41% for other biases. The distribution of high risk of bias for RCTs published in the selected prosthodontic and implant dentistry journals varied among journals and ranged from 8% to 47%, which can be considered as substantial.

GET.ON Mood Enhancer: efficacy of Internet-based guided self-help compared to psychoeducation for depression: an investigator-blinded randomised controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. A large number of randomised controlled trials (RCTs) have shown the efficacy of Internet-based guided self-help interventions in reducing symptoms of depression. However, study quality varies considerably. The aim of this study is to evaluate the efficacy of a new Internet-based guided self-help intervention (GET.ON Mood Enhancer) compared to online-based psychoeducation in an investigator-blinded RCT. Methods/design A RCT will be conducted to compare the efficacy of GET.ON Mood Enhancer with an active control condition receiving online psychoeducation on depression (OPD). Both treatment groups will have full access to treatment as usual. Adults with MDD (n = 128) will be recruited and randomised to one of the two conditions. Primary outcome will be observer-rated depressive symptoms (HRSD-24) by independent assessors blind to treatment conditions. Secondary outcomes include changes in self-reported depressive symptom severity, anxiety and quality of life. Additionally, potential negative effects of the treatments will systematically be evaluated on several dimensions (for example, symptom deteriorations, attitudes toward seeking psychological help, relationships and stigmatisation). Assessments will take place at baseline, 6 and 12 weeks after randomisation. Discussion This study evaluates a new Internet-based guided self-help intervention for depression using an active control condition (psychoeducation-control) and an independent, blinded outcome evaluation. This study will further enhance the evidence for Internet-based guided self-help interventions for MDD. Trial registration German Clinical Trial Registration (DRKS): DRKS00005025 PMID:24476555

Working memory for vibrotactile frequencies: comparison of cortical activity in blind and sighted individuals.

PubMed

Burton, Harold; Sinclair, Robert J; Dixit, Sachin

2010-11-01

In blind, occipital cortex showed robust activation to nonvisual stimuli in many prior functional neuroimaging studies. The cognitive processes represented by these activations are not fully determined, although a verbal recognition memory role has been demonstrated. In congenitally blind and sighted (10 per group), we contrasted responses to a vibrotactile one-back frequency retention task with 5-s delays and a vibrotactile amplitude-change task; both tasks involved the same vibration parameters. The one-back paradigm required continuous updating for working memory (WM). Findings in both groups confirmed roles in WM for right hemisphere dorsolateral prefrontal (DLPFC) and dorsal/ventral attention components of posterior parietal cortex. Negative findings in bilateral ventrolateral prefrontal cortex suggested task performance without subvocalization. In bilateral occipital cortex, blind showed comparable positive responses to both tasks, whereas WM evoked large negative responses in sighted. Greater utilization of attention resources in blind were suggested as causing larger responses in dorsal and ventral attention systems, right DLPFC, and persistent responses across delays between trials in somatosensory and premotor cortex. In sighted, responses in somatosensory and premotor areas showed iterated peaks matched to stimulation trial intervals. The findings in occipital cortex of blind suggest that tactile activations do not represent cognitive operations for nonverbal WM task. However, these data suggest a role in sensory processing for tactile information in blind that parallels a similar contribution for visual stimuli in occipital cortex of sighted. © 2010 Wiley-Liss, Inc.

Trial of Naltrexone and Dextromethorphan for Gulf War Veterens’ Illness

DTIC Science & Technology

2016-03-01

held by the research pharmacist . Randomization was performed by drawing a card from a box that specified the order of administration. The study...study. The pills were administered in a randomized, double- blinded fashion. The code for the blinding was held by the research pharmacist

RESEARCH BULLETIN. NUMBER 4.

ERIC Educational Resources Information Center

CLARK, LESLIE L., ED.

THE FOLLOWING FOUR RESEARCH REPORTS ON ORIENTATION AND MOBILITY FOR THE BLIND BASED ON AURAL INFORMATION ARE CONTAINED IN THIS BULLETIN--"A PSYCHOACOUSTIC STUDY OF FACTORS AFFECTING HUMAN ECHOLOCATION" BY JOHN R. WELCH, "ORIENTATION BY AURAL CLUES" BY IVO KOHLER, "SONAR SYSTEM OF THE BLIND" BY WINTHROP N. KELLOGG, AND "TRIAL OF AN ACOUSTIC BLIND…

Analysis of Parent, Teacher, and Consultant Speech Exchanges and Educational Outcomes of Students With Autism During COMPASS Consultation.

PubMed

Ruble, Lisa; Birdwhistell, Jessie; Toland, Michael D; McGrew, John H

2011-01-01

The significant increase in the numbers of students with autism combined with the need for better trained teachers (National Research Council, 2001) call for research on the effectiveness of alternative methods, such as consultation, that have the potential to improve service delivery. Data from 2 randomized controlled single-blind trials indicate that an autism-specific consultation planning framework known as the collaborative model for promoting competence and success (COMPASS) is effective in increasing child Individual Education Programs (IEP) outcomes (Ruble, Dal-rymple, & McGrew, 2010; Ruble, McGrew, & Toland, 2011). In this study, we describe the verbal interactions, defined as speech acts and speech act exchanges that take place during COMPASS consultation, and examine the associations between speech exchanges and child outcomes. We applied the Psychosocial Processes Coding Scheme (Leaper, 1991) to code speech acts. Speech act exchanges were overwhelmingly affiliative, failed to show statistically significant relationships with child IEP outcomes and teacher adherence, but did correlate positively with IEP quality.

Analysis of Parent, Teacher, and Consultant Speech Exchanges and Educational Outcomes of Students With Autism During COMPASS Consultation

PubMed Central

RUBLE, LISA; BIRDWHISTELL, JESSIE; TOLAND, MICHAEL D.; MCGREW, JOHN H.

2011-01-01

The significant increase in the numbers of students with autism combined with the need for better trained teachers (National Research Council, 2001) call for research on the effectiveness of alternative methods, such as consultation, that have the potential to improve service delivery. Data from 2 randomized controlled single-blind trials indicate that an autism-specific consultation planning framework known as the collaborative model for promoting competence and success (COMPASS) is effective in increasing child Individual Education Programs (IEP) outcomes (Ruble, Dal-rymple, & McGrew, 2010; Ruble, McGrew, & Toland, 2011). In this study, we describe the verbal interactions, defined as speech acts and speech act exchanges that take place during COMPASS consultation, and examine the associations between speech exchanges and child outcomes. We applied the Psychosocial Processes Coding Scheme (Leaper, 1991) to code speech acts. Speech act exchanges were overwhelmingly affiliative, failed to show statistically significant relationships with child IEP outcomes and teacher adherence, but did correlate positively with IEP quality. PMID:22639523

Amoxicillin pulsatile - MiddleBrook: APC 111, APC-111, PULSYS-enhanced amoxicillin.

PubMed

2007-01-01

MiddleBrook Pharmaceuticals (formerly Advancis Pharmaceutical) is developing an improved version of amoxicillin using its pulsatile oral drug delivery technology, called PULSYS. Amoxicillin PULSYS is intended to provide a lower treatment dose, once-daily alternative to currently approved amoxicillin and penicillin regimens for the treatment of adolescents/adults with pharyngitis and/or tonsillitis. If amoxicillin PULSYS is approved, it will be the first and only once-daily amoxicillin therapy approved for use in the US. Regulatory submissions for the treatment of pharyngitis/tonsillitis have been made in the US. Amoxicillin PULSYS is in clinical development for the treatment of pharyngitis and/or tonsillitis due to group A streptococcal infections in adolescents/adults as a tablet formulation. MiddleBrook was conducting clinical development of a sprinkle formulation for children. However, this has been put on hold for financial reasons. MiddleBrook is seeking regulatory approval for this product as a 505(b)(2) product, which is one that is not considered to be a completely new product, but is also not a generic product. It is a product with some differences from a previously approved product and clinical data to support such differences are required; however, the basic safety and efficacy studies may have been conducted by other organisations. In June 2007, Advancis Pharmaceutical was renamed as MiddleBrook Pharmaceuticals, Inc. MiddleBrook and Par Pharmaceuticals entered a co-promotion agreement for this product in June 2004. Par was to fund future development in exchange for co-exclusive marketing rights and exclusive rights to sell amoxicillin PULSYS. MiddleBrook retained responsibility for the manufacturing programme and also retained all patents and brand names and was responsible for their enforcement. However, this collaboration was subsequently terminated in August 2005 by Par Pharmaceutical. MiddleBrook received the US $4.75 million R&D reimbursement payment due in the third quarter of 2005 and expects no further payments under the collaboration. Under certain circumstances, the termination clauses of the agreement may entitle Par to receive a share of net profits up to 50% of its total US $23 million investment in the development of certain amoxicillin PULSYS products, should a product covered by the agreement be successfully commercialised. Following the end of the first quarter of 2005, MiddleBrook entered into agreements with Clonmel Healthcare Ltd (STADA Group), which will provide MiddleBrook with commercial supply of its amoxicillin PULSYS products being evaluated in phase III trials. MiddleBrook has closed US $24 million in private placement of common equity; funds will be used to support the regulatory approval process for the once-daily amoxicillin pulsatile product. The company conducted phase III trials of this once-daily pulsatile amoxicillin product for the treatment of pharyngitis/tonsillitis due to group A streptococcal infections (commonly referred to as strep throat). Two trials of a 775 mg tablet formulation were conducted in adolescent/adult populations. In December 2006, the company entered into a definitive private placement agreement, raising US $18 million in gross proceeds. It intends to use the proceeds to prepare for the potential commercial launch of amoxicillin PULSYS and to continue the development of other products. The first of the adolescent/adult phase III trials was initiated in October 2004 in the US. This double-blind, non-inferiority, pivotal trial enrolled 510 such patients who received amoxicillin PULSYS 775 mg administered in tablet form once daily for 7 days or the US FDA standard comparator regimen, penicillin 250 mg administered four times daily for 10 days. However, in June 2005, the company reported that amoxicillin PULSYS failed to achieve the primary endpoint of this trial (i.e. bacterial eradication). The company initiated the second adolescent/adult phase III trial in November 2005. This two-arm, double-blind, double-dummy, non-inferiority trial enrolled a total of 620 patients from the US and Canada. Patients received amoxicillin PULSYS (775 mg tablet once daily for 10 days) or the standard penicillin regimen previously mentioned. Top-line results presented in August 2006 showed that the desired microbiological and clinical endpoints were achieved in this trial. In addition, the trial showed that amoxicillin PULSYS achieved 85% bacterial eradication in the per-protocol population, in accordance with the FDA's guidance for approval as a first-line therapy for pharyngitis. MiddleBrook has completed a phase I dose finding trial of its paediatric 'sprinkle' formulation of amoxicillin PULSYS in healthy volunteers. The company commenced a two-arm, investigator-blinded, non-inferiority, US-based, phase III trial in Janary 2005 to evaluate a 'sprinkle' formulation of amoxicillin PULSYS among paediatric patients with acute pharyngitis/tonsillitis caused by group A streptococcal infections. The drug was administered in multiparticulate granules, designed to be sprinkled over food, in two dosages: 475 mg once daily in patients aged 6 months to 4 years, and 775 mg once daily for children aged 5-12 years. Patients were given either 7 days' treatment with amoxicillin PULSYS or penicillin VK four times daily for 10 days. The primary endpoint of the paediatric trial was the same as the adult one. However, in July 2005, the company reported that the product failed to achieve its desired microbiological and clinical endpoints (primary and secondary) in this trial. MiddleBrook was to review the full data and evaluate what steps, if any, could be taken to improve future outcomes.

Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

PubMed

Citrome, Leslie

2016-01-01

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

The Sonoma Water Evaluation Trial (SWET): A randomized drinking water intervention trial to reduce gastrointestinal illness in older adults

EPA Science Inventory

Objectives. We estimate the risk of highly credible gastrointestinal illness (HCGI) among adults 55 and older in a community drinking tap water meeting current U.S. standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 indiv...

Preoperative carbohydrate treatment for enhancing recovery after elective surgery.

PubMed

Smith, Mark D; McCall, John; Plank, Lindsay; Herbison, G Peter; Soop, Mattias; Nygren, Jonas

2014-08-14

Preoperative carbohydrate treatments have been widely adopted as part of enhanced recovery after surgery (ERAS) or fast-track surgery protocols. Although fast-track surgery protocols have been widely investigated and have been shown to be associated with improved postoperative outcomes, some individual constituents of these protocols, including preoperative carbohydrate treatment, have not been subject to such robust analysis. To assess the effects of preoperative carbohydrate treatment, compared with placebo or preoperative fasting, on postoperative recovery and insulin resistance in adult patients undergoing elective surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 3), MEDLINE (January 1946 to March 2014), EMBASE (January 1947 to March 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1980 to March 2014) and Web of Science (January 1900 to March 2014) databases. We did not apply language restrictions in the literature search. We searched reference lists of relevant articles and contacted known authors in the field to identify unpublished data. We included all randomized controlled trials of preoperative carbohydrate treatment compared with placebo or traditional preoperative fasting in adult study participants undergoing elective surgery. Treatment groups needed to receive at least 45 g of carbohydrates within four hours before surgery or anaesthesia start time. Data were abstracted independently by at least two review authors, with discrepancies resolved by consensus. Data were abstracted and documented pro forma and were entered into RevMan 5.2 for analysis. Quality assessment was performed independently by two review authors according to the standard methodological procedures expected by The Cochrane Collaboration. When available data were insufficient for quality assessment or data analysis, trial authors were contacted to request needed information. We collected trial data on complication rates and aspiration pneumonitis. We included 27 trials involving 1976 participants Trials were conducted in Europe, China, Brazil, Canada and New Zealand and involved patients undergoing elective abdominal surgery (18), orthopaedic surgery (4), cardiac surgery (4) and thyroidectomy (1). Twelve studies were limited to participants with an American Society of Anaesthesiologists grade of I-II or I-III.A total of 17 trials contained at least one domain judged to be at high risk of bias, and only two studies were judged to be at low risk of bias across all domains. Of greatest concern was the risk of bias associated with inadequate blinding, as most of the outcomes assessed by this review were subjective. Only six trials were judged to be at low risk of bias because of blinding.In 19 trials including 1351 participants, preoperative carbohydrate treatment was associated with shortened length of hospital stay compared with placebo or fasting (by 0.30 days; 95% confidence interval (CI) 0.56 to 0.04; very low-quality evidence). No significant effect on length of stay was noted when preoperative carbohydrate treatment was compared with placebo (14 trials including 867 participants; mean difference -0.13 days; 95% CI -0.38 to 0.12). Based on two trials including 86 participants, preoperative carbohydrate treatment was also associated with shortened time to passage of flatus when compared with placebo or fasting (by 0.39 days; 95% CI 0.70 to 0.07), as well as increased postoperative peripheral insulin sensitivity (three trials including 41 participants; mean increase in glucose infusion rate measured by hyperinsulinaemic euglycaemic clamp of 0.76 mg/kg/min; 95% CI 0.24 to 1.29; high-quality evidence).As reported by 14 trials involving 913 participants, preoperative carbohydrate treatment was not associated with an increase or a decrease in the risk of postoperative complications compared with placebo or fasting (risk ratio of complications 0.98, 95% CI 0.86 to 1.11; low-quality evidence). Aspiration pneumonitis was not reported in any patients, regardless of treatment group allocation. Preoperative carbohydrate treatment was associated with a small reduction in length of hospital stay when compared with placebo or fasting in adult patients undergoing elective surgery. It was found that preoperative carbohydrate treatment did not increase or decrease postoperative complication rates when compared with placebo or fasting. Lack of adequate blinding in many studies may have contributed to observed treatment effects for these subjective outcomes, which are subject to possible biases.

Methodological reporting of randomized clinical trials in respiratory research in 2010.

PubMed

Lu, Yi; Yao, Qiuju; Gu, Jie; Shen, Ce

2013-09-01

Although randomized controlled trials (RCTs) are considered the highest level of evidence, they are also subject to bias, due to a lack of adequately reported randomization, and therefore the reporting should be as explicit as possible for readers to determine the significance of the contents. We evaluated the methodological quality of RCTs in respiratory research in high ranking clinical journals, published in 2010. We assessed the methodological quality, including generation of the allocation sequence, allocation concealment, double-blinding, sample-size calculation, intention-to-treat analysis, flow diagrams, number of medical centers involved, diseases, funding sources, types of interventions, trial registration, number of times the papers have been cited, journal impact factor, journal type, and journal endorsement of the CONSORT (Consolidated Standards of Reporting Trials) rules, in RCTs published in 12 top ranking clinical respiratory journals and 5 top ranking general medical journals. We included 176 trials, of which 93 (53%) reported adequate generation of the allocation sequence, 66 (38%) reported adequate allocation concealment, 79 (45%) were double-blind, 123 (70%) reported adequate sample-size calculation, 88 (50%) reported intention-to-treat analysis, and 122 (69%) included a flow diagram. Multivariate logistic regression analysis revealed that journal impact factor ≥ 5 was the only variable that significantly influenced adequate allocation sequence generation. Trial registration and journal impact factor ≥ 5 significantly influenced adequate allocation concealment. Medical interventions, trial registration, and journal endorsement of the CONSORT statement influenced adequate double-blinding. Publication in one of the general medical journal influenced adequate sample-size calculation. The methodological quality of RCTs in respiratory research needs improvement. Stricter enforcement of the CONSORT statement should enhance the quality of RCTs.

Research outcomes and recommendations for the assessment of progression in cancer clinical trials from a PhRMA working group.

PubMed

Stone, A M; Bushnell, W; Denne, J; Sargent, D J; Amit, O; Chen, C; Bailey-Iacona, R; Helterbrand, J; Williams, G

2011-08-01

Progression free survival (PFS) is increasingly used as a primary end-point in oncology clinical trials. This paper provides recommendations for optimal trial design, conduct and analysis in situations where PFS has the potential to be an acceptable end-point for regulatory approval. These recommendations are based on research performed by the Pharmaceutical Research and Manufacturers Association (PhRMA) sponsored PFS Working Group, including the re-analysis of 28 randomised Phase III trials from 12 companies/institutions. (1) In the assessment of PFS, there is a critical distinction between measurement error that results from random variation, which by itself tends to attenuate treatment effect, versus bias which increases the probability of a false negative or false positive finding. Investigator bias can be detected by auditing a random sample of patients by blinded, independent, central review (BICR). (2) ITT analyses generally resulted in smaller treatment effects (HRs closer to 1) than analyses that censor patients for potentially informative events (such as starting other anti-cancer therapy). (3) Interval censored analyses (ICA) are more robust to time-evaluation bias than the log-rank test. A sample based BICR audit may be employed in open or partially blinded trials and should not be required in true double-blind trials. Patients should be followed until progression even if they have discontinued treatment to be consistent with the ITT principle. ICAs should be a standard sensitivity analysis to assess time-evaluation bias. Implementation of these recommendations would standardize and in many cases simplify phase III oncology clinical trials that use a PFS primary end-point. Copyright © 2011 Elsevier Ltd. All rights reserved.

HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Gathier, C S; van den Bergh, W M; Slooter, A J C

2014-04-01

Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Blinded sample size re-estimation in three-arm trials with 'gold standard' design.

PubMed

Mütze, Tobias; Friede, Tim

2017-10-15

In this article, we study blinded sample size re-estimation in the 'gold standard' design with internal pilot study for normally distributed outcomes. The 'gold standard' design is a three-arm clinical trial design that includes an active and a placebo control in addition to an experimental treatment. We focus on the absolute margin approach to hypothesis testing in three-arm trials at which the non-inferiority of the experimental treatment and the assay sensitivity are assessed by pairwise comparisons. We compare several blinded sample size re-estimation procedures in a simulation study assessing operating characteristics including power and type I error. We find that sample size re-estimation based on the popular one-sample variance estimator results in overpowered trials. Moreover, sample size re-estimation based on unbiased variance estimators such as the Xing-Ganju variance estimator results in underpowered trials, as it is expected because an overestimation of the variance and thus the sample size is in general required for the re-estimation procedure to eventually meet the target power. To overcome this problem, we propose an inflation factor for the sample size re-estimation with the Xing-Ganju variance estimator and show that this approach results in adequately powered trials. Because of favorable features of the Xing-Ganju variance estimator such as unbiasedness and a distribution independent of the group means, the inflation factor does not depend on the nuisance parameter and, therefore, can be calculated prior to a trial. Moreover, we prove that the sample size re-estimation based on the Xing-Ganju variance estimator does not bias the effect estimate. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension.

PubMed

Liu, Zhao-min; Ho, Suzanne C; Chen, Yu-ming; Tang, Nelson; Woo, Jean

2014-09-01

The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Emotional wellbeing of blind patients in a pilot trial with subretinal implants.

PubMed

Peters, Tobias; Klingberg, Stefan; Zrenner, Eberhart; Wilhelm, Barbara

2013-06-01

Participation in first human applications of retinal neuroprosthesis may create psychological stress for blind retinitis pigmentosa patients. The aim of this study was to assess the emotional wellbeing of patients undergoing implantation of a subretinal implant. Nine blind patients participating in a pilot trial with subretinal implants were enlisted. The Brief Symptom Inventory (BSI), a short self-report scale of nine primary symptoms, was used to assess reaction to the psychological distress related to study participation. The number and the intensity of symptoms were analysed, and global scores for overall psychological distress (tGSI), severity of reported symptoms (tPDSI), and level number of self-reported symptoms (tPST) were calculated. The questionnaire was administered before implantation, 2-3 times during the trial and before explantation. There were no significant alterations during the trial for the average scores of the nine primary symptoms. One patient, however, showed values higher than the norm, for six subscores before implantation and for eight subscores before explantation. A significant improvement was found in both the overall psychological distress level (tGSI) and the severity of reported symptoms (tPDSI) at the final visit, compared to those at the study start. The number of self-reported symptoms (tPST) was not significantly altered. In the first ongoing pilot trial with an active, cable-bound subretinal implant, we found that trial participation and the implant procedure and subsequent testing did not have any adverse effects on the participants' emotional wellbeing. Their distress generally improved during study participation, rather than showing signs of decreased wellbeing.

Evidence for the impact of quality improvement collaboratives: systematic review

PubMed Central

2008-01-01

Objective To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care. Data sources Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases. Study selection Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes. Data synthesis Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect. Conclusions The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives. PMID:18577559

Oxytocin impedes the effect of the word blindness post-hypnotic suggestion on Stroop task performance.

PubMed

Parris, Benjamin A; Dienes, Zoltan; Bate, Sarah; Gothard, Stace

2014-07-01

The ability to enhance sensitivity to relevant (post)hypnotic suggestions has implications for creating clinically informed analogues of psychological and neuropsychological conditions and for the use of hypnotic interventions in psychological and medical conditions. The aim of this study was to test the effect of oxytocin inhalation on a post-hypnotic suggestion that previously has been shown to improve the selectivity of attention in the Stroop task. In a double-blind placebo-controlled between-subjects study, medium hypnotizable individuals performed the Stroop task under normal conditions and when they had been given a post-hypnotic suggestion that they would perceive words as meaningless symbols. In line with previous research, Stroop interference was substantially reduced by the suggestion in the placebo condition. However, contrary to expectations, oxytocin impeded the effect of the word blindness suggestion on performance. The results are explained in terms of the requirement for the re-implementation of the word blindness suggestion on a trial-by-trial basis and the need to sustain activation of the suggestion between trials. The findings contrast with a recent study showing a beneficial effect of oxytocin on sensitivity to (post)hypnotic suggestions but are consistent with findings showing a detrimental effect of oxytocin on memory processes. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

2009-01-01

The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

Partnering to run a community-based program for deaf-blind young adults.

PubMed

Riester, A E

1992-12-01

Community-based programs that assist deaf-blind young adults with living skills can be a cost effective alternative to institutional care. Their unique medical, psychosocial training, and daily living needs require services and support from a variety of agencies and providers. The elements and concepts necessary to conduct a program 24 hours a day for young adults who are deaf and blind includes sound management, realistic staff expectations for clients, developmentally appropriate activities, family participation in planning accessible medical and psychological services, and close collaboration with universities and community organizations. Management must also be sensitive to the emotional concerns of the staff and provide ongoing opportunities for supervision and training.

Engaging blind and partially sighted stakeholders in transformational change.

PubMed

Pearson, Victoria

2016-09-01

For non-profit organizations in the disability sector, engaging stakeholders with disabilities on matters of strategic planning is both a responsibility and an expectation. As part of our current strategic plan, which calls for organizational and systemic transformation, the Canadian National Institute for the Blind (CNIB) has engaged blind and partially sighted stakeholders alongside other interest groups to build and advocate for a more holistic model of vision healthcare and rehabilitation. This article describes the CNIB's multi-year process, including early-stage consultations, collaborative strategy development, and political advocacy and shares our organization's key success factors and learnings in creating meaningful, mutually beneficial engagement. © 2016 The Canadian College of Health Leaders.

Projecting Event-Based Analysis Dates in Clinical Trials: An Illustration Based on the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration. Projecting analysis dates for the IDEA collaboration

PubMed Central

Renfro, Lindsay A.; Grothey, Axel M.; Paul, James; Floriani, Irene; Bonnetain, Franck; Niedzwiecki, Donna; Yamanaka, Takeharu; Souglakos, Ioannis; Yothers, Greg; Sargent, Daniel J.

2015-01-01

Purpose Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. Patients and Methods In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Results Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Conclusions Real-time projection of the final analysis time during a trial, or the overall analysis time during a trial collaborative such as IDEA, has practical implications for trial feasibility when these projections are translated into additional time and resources required. PMID:26989447

Global Collaboration in Acute Care Clinical Research: Opportunities, Challenges, and Needs.

PubMed

Marshall, John C

2017-02-01

The most impactful research in critical care comes from trials groups led by clinician-investigators who study questions arising through the day-to-day care of critically ill patients. The success of this model reflects both "necessity"-the paucity of new therapies introduced through industry-led research-and "clinical reality"-nuanced modulation of standard practice can have substantial impact on clinically important outcomes. Success in a few countries has fueled efforts to build similar models around the world and to collaborate on an unprecedented scale in large international trials. International collaboration brings opportunity-the more rapid completion of clinical trials, enhanced generalizability of the results of these trials, and a focus on questions that have evoked international curiosity. It has changed practice, improved outcomes, and enabled an international response to pandemic threats. It also brings challenges. Investigators may feel threatened by the loss of autonomy inherent in collaboration, and appropriate models of academic credit are yet to be developed. Differences in culture, practice, ethical frameworks, research experience, and resource availability create additional imbalances. Patient and family engagement in research is variable and typically inadequate. Funders are poorly equipped to evaluate and fund international collaborative efforts. Yet despite or perhaps because of these challenges, the discipline of critical care is leading the world in crafting new models of clinical research collaboration that hold the promise of not only improving the care of the most vulnerable patients in the healthcare system but also transforming the way that we conduct clinical research.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

PubMed Central

Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V.; Sleeper, Lynn A.; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D.; Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.; De Backer, Julie; De Paepe, Anne M.; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D.; Mullen, Michael J.; Child, Anne H.; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B.; Creager, Mark A.; Devereux, Richard B.; Loeys, Bart; Forfar, J. Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C.; Baigent, Colin

2015-01-01

Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). PMID:25965707

Double-blind comparative trial of indoprofen and acetylsalicylic acid in osteoarthritis.

PubMed

Katona, G

1981-01-01

The effectiveness, safety and acceptability of indoprofen (IP) and acetylsalicylic acid (ASA) were assessed in patients with osteoarthritis, in a double-blind comparative trial. Each patient received IP 600 mg/day or ASA 2100 mg/day for a four-week period; after a one-week wash-out period, the same drug was given at a higher dosage (IP 800 or ASA 2800 mg/day) for another four weeks. Seventeen patients on indoprofen and 14 on SAS completed the trial. A significant improvement was obtained with indoprofen in the different parameters measuring pain, from the first treatment period; results were similar at the end of the second period. Results with ASA, at both dosages, appeared less impressive. Two patients on indoprofen and five on ASA complained of side effects.

[Thinking on designation of sham acupuncture in clinical research].

PubMed

Pan, Li-Jia; Chen, Bo; Zhao, Xue; Guo, Yi

2014-01-01

Randomized controlled trials (RCT) is the source of the raw data of evidence-based medicine. Blind method is adopted in most of the high-quality RCT. Sham acupuncture is the main form of blinded in acupuncture clinical trial. In order to improve the quality of acupuncture clinical trail, based on the necessity of sham acupuncture in clinical research, the current situation as well as the existing problems of sham acupuncture, suggestions were put forward from the aspects of new way and new designation method which can be adopted as reference, and factors which have to be considered during the process of implementing. Various subjective and objective factors involving in the process of trial should be considered, and used of the current international standards, try to be quantification, and carry out strict quality monitoring.

A systematic review of randomised controlled trials evaluating the effect of mother/baby skin-to-skin care on successful breast feeding.

PubMed

Carfoot, Sue; Williamson, Paula R; Dickson, Rumona

2003-06-01

to examine the effects of early skin-to-skin contact between mother and baby on the initiation and duration of breast feeding. electronic databases--the Cochrane Library, MEDLINE,CINAHL and EMBASE. References of studies were examined to identify additional trials and contact was made with researchers in the field. Study selection criteria: randomised or quasi-randomised controlled trials in any language in which skin-to-skin contact between mothers and their healthy full-term newborn babies was compared to routine contact. Primary outcomes were success of first breast feed and duration of breast feeding. Secondary outcomes included, baby temperature and behaviour. STUDY-QUALITY ASSESSMENT: validity of included studies was assessed using criteria defined by the Cochrane Collaboration. Application of inclusion criteria, validity assessment and data extraction were carried out independently by two reviewers with a third reviewer to resolve differences. seven randomised controlled trials were identified. Five studies assessed duration of breast feeding with mixed results. None of the studies assessed the success of the first breast-feeding experience. Study quality was variable with methods of randomisation and blinding of assessment unclear in four of the five studies providing relevant results. the findings of this systematic review fail to support the current initiatives to implement changes in clinical practice to include skin-to-skin contact. Methodological flaws within the included studies prohibit firm conclusions being reached with regard to the effect of skin-to-skin contact on the duration of breast feeding, timing of first breast feed or baby physiological factors. The review highlights the need for further primary research to assess the effect of skin-to-skin contact on the breast-feeding experience.

Medial tibial stress syndrome: evidence-based prevention.

PubMed

Craig, Debbie I

2008-01-01

Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32-40. Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Studies were identified by searching MEDLINE (1966-2000), Current Contents (1996-2000), Biomedical Collection (1993-1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury.

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Now You See It, Now You Don't: Repetition Blindness for Nonwords

ERIC Educational Resources Information Center

Morris, Alison L.; Still, Mary L.

2008-01-01

Repetition blindness (RB) for nonwords has been found in some studies, but not in others. The authors propose that the discrepancy in results is fueled by participant strategy; specifically, when rapid serial visual presentation lists are short and participants are explicitly informed that some trials will contain repetitions, participants are…

Human norovirus inactivation in oysters by high hydrostatic pressure processing: A randomized double-blinded study

USDA-ARS?s Scientific Manuscript database

This randomized, double-blinded, clinical trial assessed the effect of high hydrostatic pressure processing (HPP) on genogroup I.1 human norovirus (HuNoV) inactivation in virus-seeded oysters when ingested by subjects. The safety and efficacy of HPP treatments were assessed in three study phases wi...

High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study.

ERIC Educational Resources Information Center

Findling, Robert L.; Maxwell, Kathleen; Scotese-Wojtila, Lynette; Huang, Jie; Yamashita, Toyoko; Wiznitzer, Max

1997-01-01

Evaluation of high doses of pyridoxine and magnesium in a 10-week double-blind placebo-controlled trial with 10 patients (mean age 6 years) having autism concluded that the high doses used were ineffective in ameliorating autistic behaviors. (DB)

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

PubMed Central

2013-01-01

Background Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids. Methods/Design Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care. Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months. Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg). Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l). Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke. Primary outcome: Addenbrooke’s Cognitive Examination-Revised. Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures. Randomisation: using stratification, minimization and simple randomization. Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management. Discussion The PODCAST trial is ongoing with 78 patients recruited to date from 22 sites. Outcomes of cognitive impairment and dementia are accruing. Trial registration ISRCTN85562386 PMID:24266960

Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Granger, Christopher B; Lopes, Renato D; Hanna, Michael; Ansell, Jack; Hylek, Elaine M; Alexander, John H; Thomas, Laine; Wang, Junyuan; Bahit, M Cecilia; Verheugt, Freek; Lawrence, Jack; Xavier, Denis; Wallentin, Lars

2015-01-01

We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial. The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

A conceptual model for the development process of confirmatory adaptive clinical trials within an emergency research network.

PubMed

Mawocha, Samkeliso C; Fetters, Michael D; Legocki, Laurie J; Guetterman, Timothy C; Frederiksen, Shirley; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-06-01

Adaptive clinical trials use accumulating data from enrolled subjects to alter trial conduct in pre-specified ways based on quantitative decision rules. In this research, we sought to characterize the perspectives of key stakeholders during the development process of confirmatory-phase adaptive clinical trials within an emergency clinical trials network and to build a model to guide future development of adaptive clinical trials. We used an ethnographic, qualitative approach to evaluate key stakeholders' views about the adaptive clinical trial development process. Stakeholders participated in a series of multidisciplinary meetings during the development of five adaptive clinical trials and completed a Strengths-Weaknesses-Opportunities-Threats questionnaire. In the analysis, we elucidated overarching themes across the stakeholders' responses to develop a conceptual model. Four major overarching themes emerged during the analysis of stakeholders' responses to questioning: the perceived statistical complexity of adaptive clinical trials and the roles of collaboration, communication, and time during the development process. Frequent and open communication and collaboration were viewed by stakeholders as critical during the development process, as were the careful management of time and logistical issues related to the complexity of planning adaptive clinical trials. The Adaptive Design Development Model illustrates how statistical complexity, time, communication, and collaboration are moderating factors in the adaptive design development process. The intensity and iterative nature of this process underscores the need for funding mechanisms for the development of novel trial proposals in academic settings.

Developing a Biostatistical Collaboration Course in a Health Science Research Methodology Program

ERIC Educational Resources Information Center

Thabane, Lehana; Walter, Stephen D.; Hanna, Steven; Goldsmith, Charles H.; Pullenayegum, Eleanor

2008-01-01

Effective statistical collaboration in a multidisciplinary health research environment requires skills not taught in the usual statistics courses. Graduates often learn such collaborative skills through trial and error. In this paper, we discuss the development of a biostatistical collaboration course aimed at graduate students in a Health…

Clinical Use of Curcumin in Depression: A Meta-Analysis.

PubMed

Ng, Qin Xiang; Koh, Shawn Shao Hong; Chan, Hwei Wuen; Ho, Collin Yih Xian

2017-06-01

There is growing interest in the use of curcumin, a plant polyphenol with potent anti-inflammatory, anti-oxidant, and neuroprotective properties, as a novel antidepressant. Clinical trials have yielded conflicting conclusions pertaining to its effectiveness in depression. A meta-analysis of the topic, which has not been done until now, is therefore necessary to summarize current evidence and generate hypotheses for further research. Using the keywords [curcumin OR diferuloylmethane OR curcuminoid OR turmeric OR Indian saffron] AND [depression OR MDD OR suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine database yielded 2081 articles published in English between January 1, 1960, and August 1, 2016. Six clinical trials with a total of 377 patients were reviewed, comparing the use of curcumin to placebo. In patients with depression, the pooled standardized mean difference from baseline Hamilton Rating Scale for Depression scores (pooled standardized mean difference -0.344, 95% confidence interval -0.558 to -0.129; P = .002) support the significant clinical efficacy of curcumin in ameliorating depressive symptoms. Significant anti-anxiety effects were also reported in 3 of the trials. Notably, no adverse events were reported in any of the trials. Most trials had a generally low risk of bias, except for an open trial of curcumin and a single-blinded study. Because of the small number of studies available, a funnel plot or sensitivity analysis was not possible. Evidence on the long-term efficacy and safety of curcumin is also limited as the duration of all available studies ranged from 4 to 8 weeks. Curcumin appears to be safe, well-tolerated, and efficacious among depressed patients. More robust randomized controlled trials with larger sample sizes and follow-up studies carried out over a longer duration should be planned to ascertain its benefits. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

The Norwegian Cervical Arthroplasty Trial (NORCAT): 2-year clinical outcome after single-level cervical arthroplasty versus fusion-a prospective, single-blinded, randomized, controlled multicenter study.

PubMed

Sundseth, Jarle; Fredriksli, Oddrun Anita; Kolstad, Frode; Johnsen, Lars Gunnar; Pripp, Are Hugo; Andresen, Hege; Myrseth, Erling; Müller, Kay; Nygaard, Øystein P; Zwart, John-Anker

2017-04-01

Standard surgical treatment for symptomatic cervical disc disease has been discectomy and fusion, but the use of arthroplasty, designed to preserve motion, has increased, and most studies report clinical outcome in its favor. Few of these trials, however, blinded the patients. We, therefore, conducted the Norwegian Cervical Arthroplasty Trial, and present 2-year clinical outcome after arthroplasty or fusion. This multicenter trial included 136 patients with single-level cervical disc disease. The patients were randomized to arthroplasty or fusion, and blinded to the treatment modality. The surgical team was blinded to randomization until nerve root decompression was completed. Primary outcome was the self-rated Neck Disability Index. Secondary outcomes were the numeric rating scale for pain and quality of life questionnaires Short Form-36 and EuroQol-5Dimension-3 Level. There was a significant improvement in the primary and all secondary outcomes from baseline to 2-year follow-up for both arthroplasty and fusion (P < 0.001), and no observed significant between-group differences at any follow-up times. However, linear mixed model analyses, correcting for baseline values, dropouts and missing data, revealed a difference in Neck Disability Index (P = 0.049), and arm pain (P = 0.027) in favor of fusion at 2 years. The duration of surgery was longer (P < 0.001), and the frequency of reoperations higher (P = 0.029) with arthroplasty. The present study showed excellent clinical results and no significant difference between treatments at any scheduled follow-up. However, the rate of index level reoperations was higher and the duration of surgery longer with arthroplasty. http://www.clinicaltrials.gov NCT 00735176.19.

Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Low back pain is a prevalent and debilitating condition that affects the health and quality of life of older adults. Older people often consult primary care physicians about back pain, with many also receiving concurrent care from complementary and alternative medicine providers, most commonly doctors of chiropractic. However, a collaborative model of treatment coordination between these two provider groups has yet to be tested. The primary aim of the Collaborative Care for Older Adults Clinical Trial is to develop and evaluate the clinical effectiveness and feasibility of a patient-centered, collaborative care model with family medicine physicians and doctors of chiropractic for the treatment of low back pain in older adults. Methods/design This pragmatic, pilot randomized controlled trial will enroll 120 participants, age 65 years or older with subacute or chronic low back pain lasting at least one month, from a community-based sample in the Quad-Cities, Iowa/Illinois, USA. Eligible participants are allocated in a 1:1:1 ratio to receive 12 weeks of medical care, concurrent medical and chiropractic care, or collaborative medical and chiropractic care. Primary outcomes are self-rated back pain and disability. Secondary outcomes include general and functional health status, symptom bothersomeness, expectations for treatment effectiveness and improvement, fear avoidance behaviors, depression, anxiety, satisfaction, medication use and health care utilization. Treatment safety and adverse events also are monitored. Participant-rated outcome measures are collected via self-reported questionnaires and computer-assisted telephone interviews at baseline, and at 4, 8, 12, 24, 36 and 52 weeks post-randomization. Provider-rated expectations for treatment effectiveness and participant improvement also are evaluated. Process outcomes are assessed through qualitative interviews with study participants and research clinicians, chart audits of progress notes and content analysis of clinical trial notes. Discussion This pragmatic, pilot randomized controlled trial uses a mixed method approach to evaluate the clinical effectiveness, feasibility, and participant and provider perceptions of collaborative care between medical doctors and doctors of chiropractic in the treatment of older adults with low back pain. Trial registration This trial registered in ClinicalTrials.gov on 04 March 2011 with the ID number of NCT01312233. PMID:23324133

Control charts for monitoring accumulating adverse event count frequencies from single and multiple blinded trials.

PubMed

Gould, A Lawrence

2016-12-30

Conventional practice monitors accumulating information about drug safety in terms of the numbers of adverse events reported from trials in a drug development program. Estimates of between-treatment adverse event risk differences can be obtained readily from unblinded trials with adjustment for differences among trials using conventional statistical methods. Recent regulatory guidelines require monitoring the cumulative frequency of adverse event reports to identify possible between-treatment adverse event risk differences without unblinding ongoing trials. Conventional statistical methods for assessing between-treatment adverse event risks cannot be applied when the trials are blinded. However, CUSUM charts can be used to monitor the accumulation of adverse event occurrences. CUSUM charts for monitoring adverse event occurrence in a Bayesian paradigm are based on assumptions about the process generating the adverse event counts in a trial as expressed by informative prior distributions. This article describes the construction of control charts for monitoring adverse event occurrence based on statistical models for the processes, characterizes their statistical properties, and describes how to construct useful prior distributions. Application of the approach to two adverse events of interest in a real trial gave nearly identical results for binomial and Poisson observed event count likelihoods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Transfer of learning on a spatial memory task between the blind and sighted people.

PubMed

Akpinar, Selcuk; Popović, Stevo; Kirazci, Sadettin

2012-12-01

The purpose of this study was to analyze the effect of two different types of feedback on a spatial memory task between the blind and blindfolded-sighted participants. Participants tried to estimate the predetermined distance by using their dominant hands. Both blind and blindfolded-sighted groups were randomly divided into two feedback subgroups as "100% frequency" and "10% bandwidth". The score of the participants was given verbally to the participants as knowledge of results (KR). The target distance was set as 60 cm. Sixty acquisition trials were performed in 4 sets each including 15 repetition afterwards immediate and delayed retention tests were undertaken. Moreover, 24 hours past the delayed retention test, the participants completed 15 no-KR trials as a transfer test (target distance was 30 cm). The results of the statistical analyses revealed no significant differences for both acquisition and retention tests. However, a significant difference was found at transfer test. 100% frequency blind group performed significantly less accurate than all other groups. As a result, it can be concluded that different types of feedback have similar effect on spatial memory task used in this study. However, types of feedback can change the performance of accuracy on transferring this skill among the blind.

Verification of the change blindness phenomenon while managing critical events on a combat information display.

PubMed

DiVita, Joseph; Obermayer, Richard; Nugent, William; Linville, James M

2004-01-01

Change blindness occurs when humans are unable to detect significant changes in objects and scenes after their attention is momentarily diverted. Because change blindness is relevant in many applied settings, the current study investigated the phenomenon in the context of tasks performed by naval command and control system personnel. Operators of such systems are often heavily loaded with concurrent visual search, situation assessment, voice communications, and control-display manipulation tasks at large, physically dispersed tactical situation displays. As the operators' attention shifts from one display to another, it creates an opportunity for changes to occur on unattended screens with potentially negative consequences. Our results show that on a display containing 8 objects of interest, considerable change blindness was demonstrated in that participants required 2 or more selections to correctly identify a changed object on nearly 1/3 of the test trials. Further, operator performance on 15% of the trials was equivalent to randomly guessing with replacement after making 3 incorrect selections. This research underscores the need for developing effective countermeasures to the change blindness phenomenon. Actual or potential uses of this research include interface design of computer workstations for military, nuclear power industry, air traffic control, crisis response center, and hospital emergency room applications.

Response-specifying cue for action interferes with perception of feature-sharing stimuli.

PubMed

Nishimura, Akio; Yokosawa, Kazuhiko

2010-06-01

Perceiving a visual stimulus is more difficult when a to-be-executed action is compatible with that stimulus, which is known as blindness to response-compatible stimuli. The present study explored how the factors constituting the action event (i.e., response-specifying cue, response intention, and response feature) affect the occurrence of this blindness effect. The response-specifying cue varied along the horizontal and vertical dimensions, while the response buttons were arranged diagonally. Participants responded based on one dimension randomly determined in a trial-by-trial manner. The response intention varied along a single dimension, whereas the response location and the response-specifying cue varied within both vertical and horizontal dimensions simultaneously. Moreover, the compatibility between the visual stimulus and the response location and the compatibility between that stimulus and the response-specifying cue was separately determined. The blindness effect emerged exclusively based on the feature correspondence between the response-specifying cue of the action task and the visual target of the perceptual task. The size of this stimulus-stimulus (S-S) blindness effect did not differ significantly across conditions, showing no effect of response intention and response location. This finding emphasizes the effect of stimulus factors, rather than response factors, of the action event as a source of the blindness to response-compatible stimuli.

Barack Obama Blindness (BOB): Absence of Visual Awareness to a Single Object.

PubMed

Persuh, Marjan; Melara, Robert D

2016-01-01

In two experiments, we evaluated whether a perceiver's prior expectations could alone obliterate his or her awareness of a salient visual stimulus. To establish expectancy, observers first made a demanding visual discrimination on each of three baseline trials. Then, on a fourth, critical trial, a single, salient and highly visible object appeared in full view at the center of the visual field and in the absence of any competing visual input. Surprisingly, fully half of the participants were unaware of the solitary object in front of their eyes. Dramatically, observers were blind even when the only stimulus on display was the face of U.S. President Barack Obama. We term this novel, counterintuitive phenomenon, Barack Obama Blindness (BOB). Employing a method that rules out putative memory effects by probing awareness immediately after presentation of the critical stimulus, we demonstrate that the BOB effect is a true failure of conscious vision.

Barack Obama Blindness (BOB): Absence of Visual Awareness to a Single Object

PubMed Central

Persuh, Marjan; Melara, Robert D.

2016-01-01

In two experiments, we evaluated whether a perceiver’s prior expectations could alone obliterate his or her awareness of a salient visual stimulus. To establish expectancy, observers first made a demanding visual discrimination on each of three baseline trials. Then, on a fourth, critical trial, a single, salient and highly visible object appeared in full view at the center of the visual field and in the absence of any competing visual input. Surprisingly, fully half of the participants were unaware of the solitary object in front of their eyes. Dramatically, observers were blind even when the only stimulus on display was the face of U.S. President Barack Obama. We term this novel, counterintuitive phenomenon, Barack Obama Blindness (BOB). Employing a method that rules out putative memory effects by probing awareness immediately after presentation of the critical stimulus, we demonstrate that the BOB effect is a true failure of conscious vision. PMID:27047362

Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.

PubMed

Mulford, Jonathan S; Watson, Anna; Broe, David; Solomon, Michael; Loefler, Andreas; Harris, Ian

2016-03-01

The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia. © 2015 Royal Australasian College of Surgeons.

Obstacle Crossing Differences Between Blind and Blindfolded Subjects After Haptic Exploration.

PubMed

Forner-Cordero, Arturo; Garcia, Valéria D; Rodrigues, Sérgio T; Duysens, Jacques

2016-01-01

Little is known about the ability of blind people to cross obstacles after they have explored haptically their size and position. Long-term absence of vision may affect spatial cognition in the blind while their extensive experience with the use of haptic information for guidance may lead to compensation strategies. Seven blind and 7 sighted participants (with vision available and blindfolded) walked along a flat pathway and crossed an obstacle after a haptic exploration. Blind and blindfolded subjects used different strategies to cross the obstacle. After the first 20 trials the blindfolded subjects reduced the distance between the foot and the obstacle at the toe-off instant, while the blind behaved as the subjects with full vision. Blind and blindfolded participants showed larger foot clearance than participants with vision. At foot landing the hip was more behind the foot in the blindfolded condition, while there were no differences between the blind and the vision conditions. For several parameters of the obstacle crossing task, blind people were more similar to subjects with full vision indicating that the blind subjects were able to compensate for the lack of vision.

Achieving consensus for clinical trials

PubMed Central

Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. Oliver; Walsh, Karin S.; Wolters, Pamela L.; Widemann, Brigitte C.

2013-01-01

The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

Implementation of treat-to-target in rheumatoid arthritis through a Learning Collaborative: Rationale and design of the TRACTION trial.

PubMed

Solomon, Daniel H; Lee, Sara B; Zak, Agnes; Corrigan, Cassandra; Agosti, Jenifer; Bitton, Asaf; Harrold, Leslie; Losina, Elena; Lu, Bing; Pincus, Ted; Radner, Helga; Smolen, Josef; Katz, Jeffrey N; Fraenkel, Liana

2016-08-01

Treat-to-target (TTT) is a recommended strategy in the management of rheumatoid arthritis (RA), but various data sources suggest that its uptake in routine care in the US is suboptimal. Herein, we describe the design of a randomized controlled trial of a Learning Collaborative to facilitate implementation of TTT. We recruited 11 rheumatology sites from across the US and randomized them into the following two groups: one received the Learning Collaborative intervention in Phase 1 (month 1-9) and the second formed a wait-list control group to receive the intervention in Phase 2 (months 10-18). The Learning Collaborative intervention was designed using the Model for Improvement, consisting of a Change Package with corresponding principles and action phases. Phase 1 intervention practices had nine learning sessions, collaborated using a web-based tool, and shared results of plan-do-study-act cycles and monthly improvement metrics collected at each practice. The wait-list control group sites had no intervention during Phase 1. The primary trial outcome is the implementation of TTT as measured by chart review, comparing the differences from baseline to end of Phase 1, between intervention and control sites. All intervention sites remained engaged in the Learning Collaborative throughout Phase 1, with a total of 38 providers participating. The primary trial outcome measures are currently being collected by the study team through medical record review. If the Learning Collaborative is an effective means for improving implementation of TTT, this strategy could serve as a way of implementing disseminating TTT more widely. Copyright © 2016 Elsevier Inc. All rights reserved.

Diverse attitudes to and understandings of spontaneous awakening trials: results from a statewide quality improvement collaborative*.

PubMed

Miller, Melissa A; Krein, Sarah L; George, Christine T; Watson, Sam R; Hyzy, Robert C; Iwashyna, Theodore J

2013-08-01

Spontaneous awakening trials (SATs) improve outcomes in mechanically ventilated patients, but implementation remains erratic. We examined variation in reported practice, prevalence of attitudes and fears regarding spontaneous awakening trials, and organizational practices associated with routine implementation of spontaneous awakening trials in an ICU quality improvement collaborative. Written survey. Michigan Health and Hospital Association's Keystone ICU, a quality improvement collaborative of 73 hospitals. Attendees of the yearly Keystone ICU meeting, January 2011, including nurses, physicians, hospital administrators, and other healthcare professionals. Respondents were asked about institutional characteristics, spontaneous awakening trial practice, attitudes and barriers regarding spontaneous awakening trials, and organizational cultural characteristics that might influence SAT practice. The association of organizational cultural characteristics and attitudes with reported spontaneous awakening trial use was evaluated using logistic regression. Three hundred nineteen participants attended the meeting. The survey response rate was 83.4%. Respondents reported wide variation in approach to spontaneous awakening trial performance and patient selection. 48.6% of respondents reported regular spontaneous awakening trial use, defined as greater than 75% of mechanically ventilated patients undergoing spontaneous awakening trials each day. In bivariable analysis, addressing sedation goals routinely in rounds and having spontaneous awakening trials as part of unit culture were positively associated with regular spontaneous awakening trial use, whereas the perception that spontaneous awakening trials increased short-term adverse effects, staff fears of spontaneous awakening trials, and the perception that spontaneous awakening trials are hard work were negatively associated with regular spontaneous awakening trial use. In multivariable analysis, only addressing sedation in rounds (odds ratio, 2.85 [95% CI, 1.55-5.23]), incorporation of spontaneous awakening trials into unit culture (odds ratio, 3.36 [95% CI, 1.75-6.43]), and the perception that spontaneous awakening trials are hard work (odds ratio, 0.53 [95% CI, 0.30-0.96]) remained statistically significantly associated with regular spontaneous awakening trial use. Respondents in managerial positions were less likely to perceive spontaneous awakening trials as hard work (odds ratio, 0.44 [95% CI, 0.22-0.85]). Even in a motivated statewide quality improvement collaborative, spontaneous awakening trial practice varies widely and concerns persist regarding spontaneous awakening trials. Cultural practices may counteract the effect of concerns regarding spontaneous awakening trials and are associated with increased performance of this beneficial intervention. Patient selection should be a focus for continuing medical education. Differences in perception of work between management and staff may also be a focus for improved communication.

Aripiprazole for the maintenance treatment of bipolar I disorder: A review.

PubMed

McIntyre, Roger S

2010-01-01

Bipolar disorder is a chronic neuropsychiatric syndrome associated with substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Metabolic comorbidity (eg, overweight, obesity, metabolic syndrome) differentially affects individuals with bipolar disorder and contributes to increased illness-associated morbidity and mortality (ie, cardiovascular disease). Few pharmacologic agents have been approved by the US Food and Drug Administration for the maintenance treatment of bipolar disorder. This paper discusses the metabolic profile of aripiprazole and reviews pivotal registration trials of aripiprazole for the maintenance treatment of adults with bipolar I disorder. MEDLINE was searched for English-language articles published between January 1995 and November 2009. The key search term was aripiprazole, combined with bipolar disorder and maintenance treatment. The review was limited to randomized, controlled registration trials, supplemented by poster presentations involving the registration-trial data sets. Three studies of the efficacy and tolerability of aripiprazole monotherapy in the maintenance treatment of bipolar I disorder were identified by the literature search: a 26-week, randomized, double-blind study and its 74-week extension phase (for a total of 100 weeks of double-blind treatment), and a randomized, double-blind comparison of aripiprazole with placebo and lithium (internal comparator) for up to 12 weeks. After 100 weeks of double-blind treatment, aripiprazole had a minimal effect on body composition and did not disrupt metabolic parameters compared with placebo. The mean (SD) weight change was 0.4 (0.8) kg with aripiprazole and -1.9 (0.8) kg with placebo (P = NS). A clinically significant (> or =7%) increase in weight occurred in 20% of the aripiprazole group and 5% of the placebo group (P = 0.01). Extrapyramidal symptoms were reported in 22% of the aripiprazole group and 15% of the placebo group. The identified trials of aripiprazole primarily enrolled patients during a manic state; no maintenance trials of combination therapy or trials enrolling individuals presenting with an acute depressive episode were identified. The available evidence supports the efficacy and tolerability of aripiprazole in the maintenance treatment of bipolar disorder. The placebo-subtracted differences in body composition and metabolic parameters suggest utility for aripiprazole in the long-term treatment of bipolar disorder. 2010 Excerpta Medica Inc. All rights reserved.

Impact on caesarean section rates following injections of sterile water (ICARIS): a multicentre randomised controlled trial.

PubMed

Lee, Nigel; Mårtensson, Lena B; Homer, Caroline; Webster, Joan; Gibbons, Kristen; Stapleton, Helen; Dos Santos, Natalie; Beckmann, Michael; Gao, Yu; Kildea, Sue

2013-05-03

Sterile water injections have been used as an effective intervention for the management of back pain during labour. The objective of the current research is to determine if sterile water injections, as an intervention for back pain in labour, will reduce the intrapartum caesarean section rate. A double blind randomised placebo controlled trialSetting: Maternity hospitals in AustraliaParticipants: 1866 women in labour, ≥18 years of age who have a singleton pregnancy with a fetus in a cephalic presentation at term (between 37 + 0 and 41 + 6 weeks gestation), who assess their back pain as equal to or greater than seven on a visual analogue scale when requesting analgesia and able to provide informed consent. Participants will be randomised to receive either 0.1 to 0.3 millilitres of sterile water or a normal saline placebo via four intradermal injections into four anatomical points surrounding the Michaelis' rhomboid over the sacral area. Two injections will be administered over the posterior superior iliac spine (PSIS) and the remaining two at two centimetres posterior, and one centimetre medial to the PSIS respectively. Proportion of women who have a caesarean section in labour.Randomisation: Permuted blocks stratified by research site.Blinding (masking):Double-blind trial in which participants, clinicians and research staff blinded to group assignment. Funded by the National Health and Medical Research CouncilTrial registration:Australian New Zealand Clinical Trials Registry (No ACTRN12611000221954). Sterile water injections, which may have a positive effect on reducing the CS rate, have been shown to be a safe and simple analgesic suitable for most maternity settings. A procedure that could reduce intervention rates without adversely affecting safety for mother and baby would benefit Australian families and taxpayers and would reduce requirements for maternal operating theatre time. Results will have external validity, as the technique may be easily applied to maternity populations outside Australia. In summary, the results of this trial will contribute High level evidence on the impact of SWI on intrapartum CS rates and provide evidence of the analgesic effect of SWI on back pain.

Mind the gap in clinical trials: A participatory action analysis with citizen collaborators.

PubMed

Price, Amy; Liew, Su May; Kirkpatrick, Jo; Price, Jazmin; Lopreto, Taylor; Nelken, Yasmin

2017-02-01

What are the strengths, gaps, expectations, and barriers to research engagement in clinical trials as communicated through social media? Clinical trials test treatments to provide reliable information for safety and effectiveness. Trials are building blocks in which what is learned in earlier research can be used to improve treatments, compare alternatives, and improve quality of life. For 20 years, the percentages of clinical trials volunteers have decreased whereas the costs of running clinical trials have multiplied. Participants enroll in trials to access latest treatments, to help others, and to advance science, but there is growing unrest. The priorities of those running the trials differ from those of the participants, and the roles for public research involvement lack clarity. Changes to bridge these gaps in the research culture are proposed through the use of participatory action research (PAR) in which stakeholders collaborate to improve research methodology, galvanize citizen participation, multiply health knowledge, problem-solve barriers to access, and explore the value of research volunteers as collaborators. PAR enabled the inclusion of citizens as full collaborators. Social media data were gathered for 120 days until saturation was reached. De-identified data were organized into a Strengths Weaknesses, Opportunities and Threats framework and coded into themes for analysis. After the analysis, the authors prioritized potential solutions for improving research engagement. Strengths and opportunities remained constant through trial phases, disease burdens, and interventions. Threats included alienation, litigation, disparity, and shaming. Poor management and barriers to inclusion were identified as weaknesses. Opportunities included improving resource management and information quality. Barriers were minimized when relationships between staff and participants were inclusive, respectful, tolerant, and open to change. Participants' communications ranged from fulfillment through trial involvement to disparities and rights violations. PAR provides a safe space without power imbalances in which researchers and citizen worked as equals rather than as researchers and objects of research. © 2016 John Wiley & Sons, Ltd.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

PubMed Central

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-01-01

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752. PMID:29730616

Asperger syndrome and anxiety disorders (PAsSA) treatment trial: a study protocol of a pilot, multicentre, single-blind, randomised crossover trial of group cognitive behavioural therapy

PubMed Central

Langdon, Peter E; Murphy, Glynis H; Wilson, Edward; Shepstone, Lee; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra

2013-01-01

Introduction A number of studies have established that children, adolescents and adults with Asperger syndrome (AS) and high functioning autism (HFA) have significant problems with anxiety. Cognitive behavioural therapy (CBT) is an effective treatment for anxiety in a variety of clinical populations. There is a growing interest in exploring the effectiveness of CBT for people with AS who have mental health problems, but currently there are no known clinical trials involving adults with AS or HFA. Studies with children who have AS have reported some success. The current study aims to examine whether modified group CBT for clinically significant anxiety in an AS population is likely to be efficacious. Methods and analysis This study is a randomised, single-blind crossover trial. At least 36 individuals will be recruited and randomised into a treatment arm or a waiting-list control arm. During treatment, individuals will receive 3 sessions of individual CBT, followed by 21 sessions of group CBT. Primary outcome measures focus on anxiety. Secondary outcome measures focus on everyday social and psychiatric functioning, additional measures of anxiety and fear, depression, health-related quality of life and treatment cost. Assessments will be administered at pregroup and postgroup and at follow-up by researchers who are blinded to group allocation. The trial aims to find out whether or not psychological treatments for anxiety can be adapted and used to successfully treat the anxiety experienced by people with AS. Furthermore, we aim to determine whether this intervention represents good value for money. Ethics and dissemination The trial received a favourable ethical opinion from a National Health Service (NHS) Research Ethics Committee. All participants provided written informed consent. Findings will be shared with all trial participants, and the general public, as well as the scientific community. Trial Registration ISRCTN 30265294 (DOI: 10.1186/ISRCTN30265294), UKCRN 8370. PMID:23901031

Design paper: the DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of aerobic versus non-aerobic versus relaxation training for patients with light to moderate depression.

PubMed

Krogh, Jesper; Petersen, Lone; Timmermann, Michael; Saltin, Bengt; Nordentoft, Merete

2007-01-01

In western countries, the yearly incidence of depression is estimated to be 3-5% and the lifetime prevalence is 17%. In patient populations with chronic diseases the point prevalence may be 20%. Depression is associated with increased risk for various conditions such as osteoporoses, cardiovascular diseases, and dementia. WHO stated in 2000 that depression was the fourth leading cause of disease burden in terms of disability. In 2000 the cost of depression in the US was estimated to 83 billion dollars. A predominance of trials suggests that physical exercise has a positive effect on depressive symptoms. However, a meta-analysis from 2001 stated: "The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow-up." The major objective for this randomized trial is to compare the effect of non-aerobic, aerobic, and relaxation training on depressive symptoms using the blindly assessed Hamilton depression scale (HAM-D(17)) as primary outcome. The secondary outcome is the effect of the intervention on working status (i.e., lost days from work, employed/unemployed) and the tertiary outcomes consist of biological responses. The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are recruited through general practitioners and psychiatrist and randomized to three different interventions: 1) non-aerobic, -- progressive resistance training, 2) aerobic training, -- cardio respiratory fitness, and 3) relaxation training with minimal impact on strength or cardio respiratory fitness. Training for all three groups takes place twice a week for 4 months. Evaluation of patients' symptoms takes place four and 12 months after inclusion. The trial is designed to include 45 patients in each group. Statistical analysis will be done as intention to treat (all randomized patients). Results from the DEMO trial will be reported according to the CONSORT guidelines in 2008-2009.

Oxandrolone augmentation of resistance training in older women: a randomized trial

USDA-ARS?s Scientific Manuscript database

INTRODUCTION: Sarcopenia is disproportionately present in older women with disability, and optimum treatment is not clear. We conducted a double-blind, randomized, placebo-controlled trial to determine whether oxandrolone administration in elderly women improves body composition or physical function...

TUTORIAL: Development of a cortical visual neuroprosthesis for the blind: the relevance of neuroplasticity

NASA Astrophysics Data System (ADS)

Fernández, E.; Pelayo, F.; Romero, S.; Bongard, M.; Marin, C.; Alfaro, A.; Merabet, L.

2005-12-01

Clinical applications such as artificial vision require extraordinary, diverse, lengthy and intimate collaborations among basic scientists, engineers and clinicians. In this review, we present the state of research on a visual neuroprosthesis designed to interface with the occipital visual cortex as a means through which a limited, but useful, visual sense could be restored in profoundly blind individuals. We review the most important physiological principles regarding this neuroprosthetic approach and emphasize the role of neural plasticity in order to achieve desired behavioral outcomes. While full restoration of fine detailed vision with current technology is unlikely in the immediate near future, the discrimination of shapes and the localization of objects should be possible allowing blind subjects to navigate in a unfamiliar environment and perhaps even to read enlarged text. Continued research and development in neuroprosthesis technology will likely result in a substantial improvement in the quality of life of blind and visually impaired individuals.

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old.

PubMed

2015-09-01

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were titered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

PubMed Central

2015-01-01

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose. PMID:26517656

Neurofeedback for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials.

PubMed

Cortese, Samuele; Ferrin, Maite; Brandeis, Daniel; Holtmann, Martin; Aggensteiner, Pascal; Daley, David; Santosh, Paramala; Simonoff, Emily; Stevenson, Jim; Stringaris, Argyris; Sonuga-Barke, Edmund J S

2016-06-01

We performed meta-analyses of randomized controlled trials to examine the effects of neurofeedback on attention-deficit/hyperactivity disorder (ADHD) symptoms and neuropsychological deficits in children and adolescents with ADHD. We searched PubMed, Ovid, Web of Science, ERIC, and CINAHAL through August 30, 2015. Random-effects models were employed. Studies were evaluated with the Cochrane Risk of Bias tool. We included 13 trials (520 participants with ADHD). Significant effects were found on ADHD symptoms rated by assessors most proximal to the treatment setting, that is, the least blinded outcome measure (standardized mean difference [SMD]: ADHD total symptoms = 0.35, 95% CI = 0.11-0.59; inattention = 0.36, 95% CI = 0.09-0.63; hyperactivity/impulsivity = 0.26, 95% CI = 0.08-0.43). Effects were not significant when probably blinded ratings were the outcome or in trials with active/sham controls. Results were similar when only frequency band training trials, the most common neurofeedback approach, were analyzed separately. Effects on laboratory measures of inhibition (SMD = 0.30, 95% CI = -0.10 to 0.70) and attention (SMD = 0.13, 95% CI = -0.09 to 0.36) were not significant. Only 4 studies directly assessed whether learning occurred after neurofeedback training. The risk of bias was unclear for many Cochrane Risk of Bias domains in most studies. Evidence from well-controlled trials with probably blinded outcomes currently fails to support neurofeedback as an effective treatment for ADHD. Future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: A pilot double-blind randomized trial [ISRCTN45683816

PubMed Central

Akhondzadeh, Shahin; Fallah-Pour, Hasan; Afkham, Khosro; Jamshidi, Amir-Hossein; Khalighi-Cigaroudi, Farahnaz

2004-01-01

Background The morbidity and mortality associated with depression are considerable and continue to increase. Depression currently ranks fourth among the major causes of disability worldwide, after lower respiratory infections, prenatal conditions, and HIV/AIDS. Crocus sativus L. is used to treat depression. Many medicinal plants textbooks refer to this indication whereas there is no evidence-based document. Our objective was to compare the efficacy of stigmas of Crocus sativus (saffron) with imipramine in the treatment of mild to moderate depression in a 6-week pilot double-blind randomized trial. Methods Thirty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive capsule of saffron 30 mg/day (TDS) (Group 1) and capsule of imipramine 100 mg/day (TDS) (Group 2) for a 6-week study. Results Saffron at this dose was found to be effective similar to imipramine in the treatment of mild to moderate depression (F = 2.91, d.f. = 1, P = 0.09). In the imipramine group anticholinergic effects such as dry mouth and also sedation were observed more often that was predictable. Conclusion The main overall finding from this study is that saffron may be of therapeutic benefit in the treatment of mild to moderate depression. To the best of our knowledge this is the first clinical trial that supports this indication for saffron. A large-scale trial with placebo control is warranted. PMID:15341662

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Wrist-ankle acupuncture (WAA) for primary dysmenorrhea (PD) of young females: study protocol for a randomized controlled trial.

PubMed

Chen, Yingfan; Tian, Sinan; Tian, Jing; Shu, Shi

2017-08-22

Primary dysmenorrhea (PD) is one of the most common health complaints all over the world, specifically among young females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, and wrist-ankle acupuncture (WAA) has confirmed analgesic efficacy for various types of pain. The aim of this study is to evaluate the immediate analgesia effect of WAA on PD of young females. This study will carry out a randomized parallel controlled single-blind trial to observe the immediate analgesia effect of WAA in PD of young females. Sixty participants who meet inclusion criteria will be recruited from September 2016 to September 2017 in Changhai hospital of China. They are randomly assigned to WAA therapy or sham acupuncture groups (30 patients for each group), and then receive real or sham acupuncture treatment, respectively. In this trial, the primary outcome measure is simple form of McGill pain questionnaire (SF-MPQ), while expectation and treatment credibility scale (ETCS), safety assessment, the COX menstrual symptom scale (CMSS), questionnaire about the feeling of being punctured are included in the secondary outcomes. This trial will be the first study protocol designed to evaluate the immediate analgesia effect of WAA in PD of young females. The strengths in methodology, including rigorous randomized, sham-controlled, participants-blinded and assessors-blinded, will guarantee the quality of this study. WAA doesn't require any needling sensation, so non-penetrating sham acupuncture can serve as an effective placebo intervention in this trial. Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-16008546 ; registration date: 27 May 2016).

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.

PubMed

Sparks, Jeffrey A; Barbhaiya, Medha; Karlson, Elizabeth W; Ritter, Susan Y; Raychaudhuri, Soumya; Corrigan, Cassandra C; Lu, Fengxin; Selhub, Jacob; Chasman, Daniel I; Paynter, Nina P; Ridker, Paul M; Solomon, Daniel H

2017-08-01

The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. CIRT will randomize up to 7000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose: 15-20mg/week) or placebo for an average follow-up period of 3-5 years; subjects in both treatment arms receive folic acid 1mg daily for 6 days each week. The primary endpoints of CIRT include recurrent cardio vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Collaboration among Grandparents and Professionals with Discrete Trial Training in the Treatment for Traumatic Brain Injury

ERIC Educational Resources Information Center

Devlin, Sandra D.; Krenzer, Daniels J.; Edwards, Jennifer

2009-01-01

This study evaluated the impact of collaborative efforts of grandparents and school professionals in the treatment of Traumatic Brain Injury in a six-year-old boy. The method of treatment was discrete trial training across settings (e.g., home and school) and the change agents were the child's grandparents, special education teacher, and a teacher…

Routine vitamin A supplementation for the prevention of blindness due to measles infection in children.

PubMed

Bello, Segun; Meremikwu, Martin M; Ejemot-Nwadiaro, Regina I; Oduwole, Olabisi

2016-08-31

Reduced vitamin A concentration increases the risk of blindness in children infected with the measles virus. Promoting vitamin A supplementation in children with measles contributes to the control of blindness in children, which is a high priority within the World Health Organization (WHO) VISION 2020 The Right to Sight Program. To assess the efficacy of vitamin A in preventing blindness in children with measles without prior clinical features of vitamin A deficiency. We searched CENTRAL 2015, Issue 11, MEDLINE (1950 to December week 3, 2015), Embase (1974 to December 2015) and LILACS (1985 to December 2015). Randomised controlled trials (RCTs) assessing the efficacy of vitamin A in preventing blindness in well-nourished children diagnosed with measles but with no prior clinical features of vitamin A deficiency. For the original review, two review authors independently assessed studies for eligibility and extracted data on reported outcomes. We contacted trial authors of the included studies for additional information on unpublished data. We included two RCTs which were clinically heterogenous. We presented the continuous outcomes reported as the mean difference (MD) with 95% confidence interval (CI) and dichotomous outcomes as risk ratio (RR) with 95% CI. Due to marked clinical heterogeneity we considered it inappropriate to perform a meta-analysis. For the first publication of this review, two RCTs involving 260 children with measles which compared vitamin A with placebo met the inclusion criteria. Neither study reported blindness or other ocular morbidities as end points. One trial of moderate quality suggested evidence of a significant increase in serum retinol levels in the vitamin A group one week after two doses of vitamin A (MD 9.45 µg/dL, 95% CI 2.19 to 16.71; 17 participants, moderate-quality evidence), but not six weeks after three doses of vitamin A (MD 2.56 µg/dL, 95% CI -5.28 to 10.40; 39 participants, moderate-quality evidence). There was no significant difference in weight gain six weeks (MD 0.39 kg, -0.04 to 0.82; 48 participants, moderate-quality evidence) and six months (MD 0.52 kg, 95% CI -0.08 to 1.12; 36 participants, moderate-quality evidence) after three doses of vitamin A.The second trial found no significant difference in serum retinol levels two weeks after a single dose of vitamin A (MD 2.67 µg/dL, 95% CI -0.29 to 5.63; 155 participants, moderate-quality evidence). Percentage of undernutrition between the two groups did not differ significantly at one week (RR 0.93, 95% CI 0.56 to 1.54, 145 participants) and two weeks (RR 0.82, 95% CI 0.52 to 1.29, 147 participants) after a single dose of vitamin A. No adverse event was reported in either study. We did not find any new RCTS for this second update. We did not find any trials assessing whether or not vitamin A supplementation in children with measles prevents blindness, as neither study reported blindness or other ocular morbidities as end points.

Aggregated data from two double-blind base station provocation studies comparing individuals with idiopathic environmental intolerance with attribution to electromagnetic fields and controls.

PubMed

Eltiti, Stacy; Wallace, Denise; Russo, Riccardo; Fox, Elaine

2015-02-01

Data from two previous studies were aggregated to provide a statistically powerful test of whether exposure to electromagnetic fields (EMFs) produced by telecommunication base stations negatively affects well-being in individuals who report idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) and control participants. A total of 102 IEI-EMF and 237 controls participated in open provocation trials and 88 IEI-EMF and 231 controls went on to complete double-blind trials in which they were exposed to EMFs from a base station emitting either a Global System for Mobile Communication and Universal Mobile Telecommunications System or a Terrestrial Trunked Radio Telecommunications System signal. Both experiments included a comparison sham condition. Visual analog and symptom scales measured subjective well-being. Results showed that IEI-EMF participants reported lower levels of well-being during real compared to sham exposure during open provocation, but not during double-blind trials. Additionally, participants reported lower levels of well-being during high compared to low load trials and this did not interact with radiofrequency-EMF exposure. These findings are consistent with a growing body of literature indicating there is no causal relationship between short-term exposure to EMFs and subjective well-being in members of the public whether or not they report perceived sensitivity to EMFs. © 2015 Wiley Periodicals, Inc.

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

Brief Report: Pilot Single-Blind Placebo Lead-in Study of Acamprosate in Youth with Autistic Disorder

ERIC Educational Resources Information Center

Erickson, Craig A.; Wink, Logan K.; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; McDougle, Christopher J.

2014-01-01

Rationale: An excitatory/inhibitory (E:I) imbalance marked by enhanced glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of autism spectrum disorders (ASD). Objectives: We report on the first single-blind placebo lead-in trial of acamprosate, a drug with putative mechanisms restoring E:I…

A method and technical equipment for an acute human trial to evaluate retinal implant technology

NASA Astrophysics Data System (ADS)

Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

2005-03-01

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 µm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial.

PubMed

Overton, Edgar Turner; Lawrence, Steven J; Wagner, Eva; Nopora, Katrin; Rösch, Siegfried; Young, Philip; Schmidt, Darja; Kreusel, Christian; De Carli, Sonja; Meyer, Thomas P; Weidenthaler, Heinz; Samy, Nathaly; Chaplin, Paul

2018-01-01

Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts. The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637. Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment. The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA. ClinicalTrials.gov NCT01144637.

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

USDA-ARS?s Scientific Manuscript database

Background: The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not l...

The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive-behavioural therapy.

PubMed

Langdon, Peter E; Murphy, Glynis H; Shepstone, Lee; Wilson, Edward C F; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

2016-03-01

There is a growing interest in using cognitive-behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. None. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.

Training tomorrow's environmental problem-solvers: an integrative approach to graduate education

USDA-ARS?s Scientific Manuscript database

Environmental problems are generally complex and blind to disciplinary boundaries. Efforts to devise long-term solutions require collaborative research that integrates knowledge across historically disparate fields, yet the traditional model for training new scientists emphasizes personal independe...

International Collaboration between US and Thailand on a Clinical Trial of Treatment for HIV-associated Cryptococcal Meningitis

PubMed Central

Zimmer, LO; Nolen, TL; Pramanpol, S; Wallace, D; Walker, ME; Pappas, P; Chetchotisakd, P

2010-01-01

Background International clinical trials can provide scientific and logistic benefits in spite of the many challenges. Determining whether a country, especially a developing country, is an appropriate location for the research should include in-country consultation and partnering to assess its social value for the population; that treatments are relevant for the population under study; and that the research infrastructure and ethical oversight are adequate. Collaboration increases the likelihood of study success and helps ensure that benefits accrue to recruited populations and their community. Purpose This paper describes our experiences on a bi-national study and may provide guidance for those planning to engage in future collaborations. Methods A Thai and United States team collaborated to develop and implement a Phase II clinical trial for HIV-associated cryptococcal meningitis to assess safety and tolerability of combination therapy versus standard treatment. Clinical and cultural differences, regulatory hurdles and operational issues were addressed before and during the study to ensure a successful collaboration between the 2 groups. Results The international multicenter study allowed for more rapid enrollment, reduced costs to complete the study, sharing of the benefits of research, greater generalizability of results and capacity building in Thailand; quality metrics in Thailand were equivalent to or better than those in the U.S. Conclusions Conducting successful clinical trials internationally requires early and ongoing collaboration to ensure the study meets sites’ requirements and expectations, conforms to varying national regulations, adheres to data quality standards and is responsive to the health needs of studied populations. PMID:19897055

Effective Online Practices for International Learning Collaborations

ERIC Educational Resources Information Center

Ray, Waverly C.; Muñiz-Solari, Osvaldo; Klein, Phil; Solem, Michael

2012-01-01

The Association of American Geographers' Center for Global Geography Education aims to internationalize geography in higher education by providing materials and activities to support international learning collaborations. From 2007-2011, geographers in different countries collaboratively developed online learning materials and trialed these…

Methodological reporting quality of randomized controlled trials: A survey of seven core journals of orthopaedics from Mainland China over 5 years following the CONSORT statement.

PubMed

Zhang, J; Chen, X; Zhu, Q; Cui, J; Cao, L; Su, J

2016-11-01

In recent years, the number of randomized controlled trials (RCTs) in the field of orthopaedics is increasing in Mainland China. However, randomized controlled trials (RCTs) are inclined to bias if they lack methodological quality. Therefore, we performed a survey of RCT to assess: (1) What about the quality of RCTs in the field of orthopedics in Mainland China? (2) Whether there is difference between the core journals of the Chinese department of orthopedics and Orthopaedics Traumatology Surgery & Research (OTSR). This research aimed to evaluate the methodological reporting quality according to the CONSORT statement of randomized controlled trials (RCTs) in seven key orthopaedic journals published in Mainland China over 5 years from 2010 to 2014. All of the articles were hand researched on Chongqing VIP database between 2010 and 2014. Studies were considered eligible if the words "random", "randomly", "randomization", "randomized" were employed to describe the allocation way. Trials including animals, cadavers, trials published as abstracts and case report, trials dealing with subgroups analysis, or trials without the outcomes were excluded. In addition, eight articles selected from Orthopaedics Traumatology Surgery & Research (OTSR) between 2010 and 2014 were included in this study for comparison. The identified RCTs are analyzed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT), including the sample size calculation, allocation sequence generation, allocation concealment, blinding and handling of dropouts. A total of 222 RCTs were identified in seven core orthopaedic journals. No trials reported adequate sample size calculation, 74 (33.4%) reported adequate allocation generation, 8 (3.7%) trials reported adequate allocation concealment, 18 (8.1%) trials reported adequate blinding and 16 (7.2%) trials reported handling of dropouts. In OTSR, 1 (12.5%) trial reported adequate sample size calculation, 4 (50.0%) reported adequate allocation generation, 1 (12.5%) trials reported adequate allocation concealment, 2 (25.0%) trials reported adequate blinding and 5 (62.5%) trials reported handling of dropouts. There were statistical differences as for sample size calculation and handling of dropouts between papers from Mainland China and OTSR (P<0.05). The findings of this study show that the methodological reporting quality of RCTs in seven core orthopaedic journals from the Mainland China is far from satisfaction and it needs to further improve to keep up with the standards of the CONSORT statement. Level III case control. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The effects of blinding on the outcomes of psychotherapy and pharmacotherapy for adult depression: A meta-analysis.

PubMed

Cuijpers, P; Karyotaki, E; Andersson, G; Li, J; Mergl, R; Hegerl, U

2015-09-01

Randomized trials with antidepressants are often run under double blind placebo-controlled conditions, whereas those with psychotherapies are mostly unblinded. This can introduce bias in favor of psychotherapy when the treatments are directly compared. In this meta-analysis, we examine this potential source of bias. We searched Pubmed, PsycInfo, Embase and the Cochrane database (1966 to January 2014) by combining terms indicative of psychological treatment and depression, and limited to randomized trials. We included 35 trials (with 3721 patients) in which psychotherapy and pharmacotherapy for adult depression were directly compared with each other. We calculated effect sizes for each study indicating the difference between psychotherapy and pharmacotherapy at post-test. Then, we examined the difference between studies with a placebo condition and those without in moderator analyses. We did not find a significant difference between the studies with and those without a placebo condition. The studies in which a placebo condition was included indicated no significant difference between psychotherapy and pharmacotherapy (g=-0.07; NNT=25). Studies in which no placebo condition was included (and patients and clinicians in both conditions were not blinded), resulted in a small, but significant difference between psychotherapy and pharmacotherapy in favor of pharmacotherapy (g=-0.13; NNT=14). Studies comparing psychotherapy and pharmacotherapy in which both groups of patients (and therapists) are not blinded (no placebo condition is included) result in a very small, but significantly higher effect for pharmacotherapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Pharmacological treatments of cerebellar ataxia.

PubMed

Ogawa, Masafumi

2004-01-01

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.

The influence of multiple trials and computer-mediated communication on collaborative and individual semantic recall.

PubMed

Hinds, Joanne M; Payne, Stephen J

2018-04-01

Collaborative inhibition is a phenomenon where collaborating groups experience a decrement in recall when interacting with others. Despite this, collaboration has been found to improve subsequent individual recall. We explore these effects in semantic recall, which is seldom studied in collaborative retrieval. We also examine "parallel CMC", a synchronous form of computer-mediated communication that has previously been found to improve collaborative recall [Hinds, J. M., & Payne, S. J. (2016). Collaborative inhibition and semantic recall: Improving collaboration through computer-mediated communication. Applied Cognitive Psychology, 30(4), 554-565]. Sixty three triads completed a semantic recall task, which involved generating words beginning with "PO" or "HE" across three recall trials, in one of three retrieval conditions: Individual-Individual-Individual (III), Face-to-face-Face-to-Face-Individual (FFI) and Parallel-Parallel-Individual (PPI). Collaborative inhibition was present across both collaborative conditions. Individual recall in Recall 3 was higher when participants had previously collaborated in comparison to recalling three times individually. There was no difference between face-to-face and parallel CMC recall, however subsidiary analyses of instance repetitions and subjective organisation highlighted differences in group members' approaches to recall in terms of organisation and attention to others' contributions. We discuss the implications of these findings in relation to retrieval strategy disruption.

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. 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/.

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

Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review

PubMed Central

Zhang, Claire Shuiqing; Tan, Hsiewe Ying; Zhang, George Shengxi; Zhang, Anthony Lin; Xue, Charlie Changli; Xie, Yi Min

2015-01-01

While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and blinding credibility. PMID:26536619

Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

PubMed

Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

2016-01-01

Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

Building a future full of opportunity for blind youths in science

NASA Astrophysics Data System (ADS)

Beck-Winchatz, B.; Riccobono, M. A.

Like their sighted peers many blind students in elementary middle and high school are naturally interested in space This interest can motivate them to learn fundamental scientific quantitative and critical thinking skills and sometimes even lead to careers in SMET disciplines However these students are often at a disadvantage in science because of the ubiquity of important graphical information that is generally not available in accessible formats the unfamiliarity of teachers with non-visual teaching methods lack of access to blind role models and the low expectations of their teachers and parents In this presentation we will describe joint efforts by NASA and the National Federation of the Blind s NFB Center for Blind Youth in Science to develop and implement strategies to promote opportunities for blind youth in science These include the development of tactile space science books and curriculum materials science academies for blind middle school and high school students internship and mentoring programs as well as research on non-visual learning techniques This partnership with the NFB exemplifies the effectiveness of collaborations between NASA and consumer-directed organizations to improve opportunities for underserved and underrepresented individuals Session participants will also have the opportunity to examine some of the recently developed tactile space science education materials themselves

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

Advancing participation of blind students in Science, Technology, Engineering, and Math

NASA Astrophysics Data System (ADS)

Beck-Winchatz, Bernhard; Riccobono, Mark A.

2008-12-01

Like their sighted peers, many blind students in elementary, middle, and high school are naturally interested in space. This interest can motivate them to learn fundamental scientific, quantitative, and critical thinking skills, and sometimes even lead to careers in Science, Technology, Engineering, and Math (STEM) disciplines. However, these students are often at a disadvantage in science because of the ubiquity of important graphical information that is generally not available in accessible formats, the unfamiliarity of teachers with non-visual teaching methods, lack of access to blind role models, and the low expectations of their teachers and parents. We discuss joint efforts by the National Aeronautics and Space Administration (NASA) and the National Federation of the Blind’s (NFB) National Center for Blind Youth in Science (NCBYS) to develop and implement strategies to promote opportunities for blind youth in science. These include the development of tactile space science books and curriculum materials, science academies for blind middle school and high school students, and college-level internship and mentoring programs. The partnership with the NFB exemplifies the effectiveness of collaborations between NASA and consumer-directed organizations to improve opportunities for underserved and underrepresented individuals.

Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

ERIC Educational Resources Information Center

Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

A Randomized Controlled Trial of the Group-Based Modified Story Memory Technique in TBI

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0726 TITLE: A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI 5b. GRANT...forthcoming, The current study addresses this need through a double blind, placebo- controlled , randomized clinical trial (RCT) of a group

The Rules of Engagement: CTTI Recommendations for Successful Collaborations Between Sponsors and Patient Groups Around Clinical Trials.

PubMed

Bloom, Diane; Beetsch, Joel; Harker, Matthew; Hesterlee, Sharon; Moreira, Paulo; Patrick-Lake, Bray; Selig, Wendy; Sherman, Jeffrey; Smith, Sophia K; Valentine, James E; Roberts, Jamie N

2018-03-01

To identify the elements necessary for successful collaboration between patient groups and academic and industry sponsors of clinical trials, in order to develop recommendations for best practices for effective patient group engagement. In-depth interviews, informed by a previously reported survey, were conducted to identify the fundamentals of successful patient group engagement. Thirty-two respondents from 3 sectors participated: patient groups, academic researchers, and industry. The findings were presented to a multistakeholder group of experts in January 2015. The expert group came to consensus on a set of actionable recommendations for best practices for patient groups and research sponsors. Interview respondents acknowledged that not all patient groups are created equal in terms of what they can contribute to a clinical trial. The most important elements for effective patient group engagement include establishing meaningful partnerships, demonstrating mutual benefits, and collaborating as partners from the planning stage forward. Although there is a growing appreciation by sponsors about the benefits of patient group engagement, there remains some resistance and some uncertainty about how best to engage. Barriers include mismatched expectations and a perception that patient groups lack scientific sophistication and that "wishful thinking" may cloud their recommendations. Patient groups are developing diverse skillsets and acquiring assets to leverage in order to become collaborators with industry and academia on clinical trials. Growing numbers of research sponsors across the clinical trials enterprise are recognizing the benefits of continuous and meaningful patient group engagement, but there are still mindsets to change, and stakeholders need further guidance on operationalizing a new model of clinical trial conduct.

Methodological reporting of randomized trials in five leading Chinese nursing journals.

PubMed

Shi, Chunhu; Tian, Jinhui; Ren, Dan; Wei, Hongli; Zhang, Lihuan; Wang, Quan; Yang, Kehu

2014-01-01

Randomized controlled trials (RCTs) are not always well reported, especially in terms of their methodological descriptions. This study aimed to investigate the adherence of methodological reporting complying with CONSORT and explore associated trial level variables in the Chinese nursing care field. In June 2012, we identified RCTs published in five leading Chinese nursing journals and included trials with details of randomized methods. The quality of methodological reporting was measured through the methods section of the CONSORT checklist and the overall CONSORT methodological items score was calculated and expressed as a percentage. Meanwhile, we hypothesized that some general and methodological characteristics were associated with reporting quality and conducted a regression with these data to explore the correlation. The descriptive and regression statistics were calculated via SPSS 13.0. In total, 680 RCTs were included. The overall CONSORT methodological items score was 6.34 ± 0.97 (Mean ± SD). No RCT reported descriptions and changes in "trial design," changes in "outcomes" and "implementation," or descriptions of the similarity of interventions for "blinding." Poor reporting was found in detailing the "settings of participants" (13.1%), "type of randomization sequence generation" (1.8%), calculation methods of "sample size" (0.4%), explanation of any interim analyses and stopping guidelines for "sample size" (0.3%), "allocation concealment mechanism" (0.3%), additional analyses in "statistical methods" (2.1%), and targeted subjects and methods of "blinding" (5.9%). More than 50% of trials described randomization sequence generation, the eligibility criteria of "participants," "interventions," and definitions of the "outcomes" and "statistical methods." The regression analysis found that publication year and ITT analysis were weakly associated with CONSORT score. The completeness of methodological reporting of RCTs in the Chinese nursing care field is poor, especially with regard to the reporting of trial design, changes in outcomes, sample size calculation, allocation concealment, blinding, and statistical methods.

Collaborative Interventions for Circulation and Depression (COINCIDE): study protocol for a cluster randomized controlled trial of collaborative care for depression in people with diabetes and/or coronary heart disease

PubMed Central

2012-01-01

Background Depression is up to two to three times as common in people with long-term conditions. It negatively affects medical management of disease and self-care behaviors, and leads to poorer quality of life and high costs in primary care. Screening and treatment of depression is increasingly prioritized, but despite initiatives to improve access and quality of care, depression remains under-detected and under-treated, especially in people with long-term conditions. Collaborative care is known to positively affect the process and outcome of care for people with depression and long-term conditions, but its effectiveness outside the USA is still relatively unknown. Furthermore, collaborative care has yet to be tested in settings that resemble more naturalistic settings that include patient choice and the usual care providers. The aim of this study was to test the effectiveness of a collaborative-care intervention, for people with depression and diabetes/coronary heart disease in National Health Service (NHS) primary care, in which low-intensity psychological treatment services are delivered by the usual care provider - Increasing Access to Psychological Therapies (IAPT) services. The study also aimed to evaluate the cost-effectiveness of the intervention over 6 months, and to assess qualitatively the extent to which collaborative care was implemented in the intervention general practices. Methods This is a cluster randomized controlled trial of 30 general practices allocated to either collaborative care or usual care. Fifteen patients per practice will be recruited after a screening exercise to detect patients with recognized depression (≥10 on the nine-symptom Patient Health Questionnaire; PHQ-9). Patients in the collaborative-care arm with recognized depression will be offered a choice of evidence-based low-intensity psychological treatments based on cognitive and behavioral approaches. Patients will be case managed by psychological well-being practitioners employed by IAPT in partnership with a practice nurse and/or general practitioner. The primary outcome will be change in depressive symptoms at 6 months on the 90-item Symptoms Checklist (SCL-90). Secondary outcomes include change in health status, self-care behaviors, and self-efficacy. A qualitative process evaluation will be undertaken with patients and health practitioners to gauge the extent to which the collaborative-care model is implemented, and to explore sustainability beyond the clinical trial. Discussion COINCIDE will assess whether collaborative care can improve patient-centered outcomes, and evaluate access to and quality of care of co-morbid depression of varying intensity in people with diabetes/coronary heart disease. Additionally, by working with usual care providers such as IAPT, and by identifying and evaluating interventions that are effective and appropriate for routine use in the NHS, the COINCIDE trial offers opportunities to address translational gaps between research and implementation. Trial Registration Number ISRCTN80309252 Trial Status Open PMID:22906179

Efficacy of paracetamol, diclofenac and advice for acute low back pain in general practice: design of a randomized controlled trial (PACE Plus).

PubMed

Schreijenberg, M; Luijsterburg, P A J; Van Trier, Y D M; Rizopoulos, D; Koopmanschap, M A; Voogt, L; Maher, C G; Koes, B W

2017-02-01

Low back pain is common and associated with a considerable burden to patients and society. There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain. This trial will assess the effectiveness of paracetamol, diclofenac and placebo for acute low back pain over a period of 4 weeks. Furthermore, this trial will assess the additional effectiveness of paracetamol, diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks. The PACE Plus trial is a multi-center, placebo-blinded, superiority randomized controlled trial in primary care, with a follow-up of 12 weeks. Patients with acute low back pain aged 18-60 years presenting in general practice will be included. Patients are randomized into four groups: 1) Advice only (usual care conforming with the clinical guideline of the Dutch College of General Practitioners); 2) Advice and paracetamol; 3) Advice and diclofenac; 4) Advice and placebo. The primary outcome is low back pain intensity measured with a numerical rating scale (0-10). Secondary outcomes include compliance to treatment, disability, perceived recovery, costs, adverse reactions, satisfaction, sleep quality, co-interventions and adequacy of blinding. Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models. An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life. Explorative analyses will be performed to assess effect modification by predefined variables. Ethical approval has been granted. Trial results will be released to an appropriate peer-viewed journal. This paper presents the design of the PACE Plus trial: a multi-center, placebo-blinded, superiority randomized controlled trial in primary care that will assess the effectiveness of advice only, paracetamol, diclofenac and placebo for acute low back pain. Dutch Trial Registration NTR6089 , registered September 14th, 2016. Version 4, June 2016.

Test-treatment RCTs are susceptible to bias: a review of the methodological quality of randomized trials that evaluate diagnostic tests.

PubMed

Ferrante di Ruffano, Lavinia; Dinnes, Jacqueline; Sitch, Alice J; Hyde, Chris; Deeks, Jonathan J

2017-02-24

There is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests. Many international bodies are calling for diagnostic randomized controlled trials to provide the most rigorous evidence of impact to patient health. Although these so-called test-treatment RCTs are very challenging to undertake due to their methodological complexity, they have not been subjected to a systematic appraisal of their methodological quality. The extent to which these trials may be producing biased results therefore remains unknown. We set out to address this issue by conducting a methodological review of published test-treatment trials to determine how often they implement adequate methods to limit bias and safeguard the validity of results. We ascertained all test-treatment RCTs published 2004-2007, indexed in CENTRAL, including RCTs which randomized patients to diagnostic tests and measured patient outcomes after treatment. Tests used for screening, monitoring or prognosis were excluded. We assessed adequacy of sequence generation, allocation concealment and intention-to-treat, appropriateness of primary analyses, blinding and reporting of power calculations, and extracted study characteristics including the primary outcome. One hundred three trials compared 105 control with 119 experimental interventions, and reported 150 primary outcomes. Randomization and allocation concealment were adequate in 57 and 37% of trials. Blinding was uncommon (patients 5%, clinicians 4%, outcome assessors 21%), as was an adequate intention-to-treat analysis (29%). Overall 101 of 103 trials (98%) were at risk of bias, as judged using standard Cochrane criteria. Test-treatment trials are particularly susceptible to attrition and inadequate primary analyses, lack of blinding and under-powering. These weaknesses pose much greater methodological and practical challenges to conducting reliable RCT evaluations of test-treatment strategies than standard treatment interventions. We suggest a cautious approach that first examines whether a test-treatment intervention can accommodate the methodological safeguards necessary to minimize bias, and highlight that test-treatment RCTs require different methods to ensure reliability than standard treatment trials. Please see the companion paper to this article: http://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0286-0 .

Collaborative evaluation of a high school prevention curriculum: How methods of collaborative evaluation enhanced a randomized control trial to inform program improvement.

PubMed

Orsini, Muhsin Michael; Wyrick, David L; Milroy, Jeffrey J

2012-11-01

Blending high-quality and rigorous research with pure evaluation practice can often be best accomplished through thoughtful collaboration. The evaluation of a high school drug prevention program (All Stars Senior) is an example of how perceived competing purposes and methodologies can coexist to investigate formative and summative outcome variables that can be used for program improvement. Throughout this project there were many examples of client learning from evaluator and evaluator learning from client. This article presents convincing evidence that collaborative evaluation can improve the design, implementation, and findings of the randomized control trial. Throughout this paper, we discuss many examples of good science, good evaluation, and other practical benefits of practicing collaborative evaluation. Ultimately, the authors created the term pre-formative evaluation to describe the period prior to data collection and before program implementation, when collaborative evaluation can inform program improvement. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Causal Model for Joint Evaluation of Placebo and Treatment-Specific Effects in Clinical Trials

PubMed Central

Zhang, Zhiwei; Kotz, Richard M.; Wang, Chenguang; Ruan, Shiling; Ho, Martin

2014-01-01

Summary Evaluation of medical treatments is frequently complicated by the presence of substantial placebo effects, especially on relatively subjective endpoints, and the standard solution to this problem is a randomized, double-blinded, placebo-controlled clinical trial. However, effective blinding does not guarantee that all patients have the same belief or mentality about which treatment they have received (or treatmentality, for brevity), making it difficult to interpret the usual intent-to-treat effect as a causal effect. We discuss the causal relationships among treatment, treatmentality and the clinical outcome of interest, and propose a causal model for joint evaluation of placebo and treatment-specific effects. The model highlights the importance of measuring and incorporating patient treatmentality and suggests that each treatment group should be considered a separate observational study with a patient's treatmentality playing the role of an uncontrolled exposure. This perspective allows us to adapt existing methods for dealing with confounding to joint estimation of placebo and treatment-specific effects using measured treatmentality data, commonly known as blinding assessment data. We first apply this approach to the most common type of blinding assessment data, which is categorical, and illustrate the methods using an example from asthma. We then propose that blinding assessment data can be collected as a continuous variable, specifically when a patient's treatmentality is measured as a subjective probability, and describe analytic methods for that case. PMID:23432119

Methodological considerations in the design and implementation of clinical trials.

PubMed

Cirrincione, Constance T; Lavoie Smith, Ellen M; Pang, Herbert

2014-02-01

To review study design issues related to clinical trials led by oncology nurses, with special attention to those conducted within the cooperative group setting; to emphasize the importance of the statistician's role in the process of clinical trials. Studies available at clinicaltrials.gov using experimental designs that have been published in peer-reviewed journals; cooperative group trials are highlighted. The clinical trial is a primary means to test intervention efficacy. A properly designed and powered study with clear and measurable objectives is as important as the intervention itself. Collaboration among the study team, including the statistician, is central in developing and conducting appropriately designed studies. For optimal results, collaboration is an ongoing process that should begin early on. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of Attention Training on Academic Achievement, Executive Functioning, and Behavior: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Kirk, Hannah; Gray, Kylie; Ellis, Kirsten; Taffe, John; Cornish, Kim

2017-01-01

Children with intellectual and developmental disabilities (IDD) experience significant difficulties in attention, learning, executive functions, and behavioral regulation. Emerging evidence suggests that computerized cognitive training may remediate these impairments. In a double blind controlled trial, 76 children with IDD (4-11 years) were…

Escitalopram in the Treatment of Adolescent Depression: A Randomized Placebo-Controlled Multisite Trial

ERIC Educational Resources Information Center

Emslie, Graham J.; Ventura, Daniel; Korotzer, Andrew; Tourkodimitris, Stavros

2009-01-01

A randomized, double-blind, placebo-controlled trial that involves 312 male and female patients aged 12-17 reveal the effectiveness of escitalopram in the treatment of depressed adolescents. Eighty-three percent of the participants or 259 participants completed the 8 weeks therapy period.

Science Activities for the Visually Impaired: Developing a Model.

ERIC Educational Resources Information Center

DeLucchi, Linda; And Others

1980-01-01

Science activities for the visually impaired (SAVI) introduces blind and visually impaired children (9 to 12 years old) to physical and life sciences in a multisensory way. Evolution of SAVI activities involves exploration, local trials, and national trials. SAVI project materials can help integrate handicapped children into the mainstream through…

PARTICIPANT BLINDING AND GASTROINTESTINAL ILLNESS IN A RANDOMIZED, CONTROLLED TRIAL OF AN IN-HOME DRINKING WATER INTERVENTION

EPA Science Inventory

Background. There is no consensus about the level of risk of gastrointestinal illness posed by consumption of drinking water that meets all regulatory requirements. Earlier drinking water intervention trials from Canada suggested that 14% - 40% of such gastrointestinal il...

Computerized Training of Working Memory in Children with ADHD-A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Klingberg, Torkel; Fernell, Elisabeth; Olesen, Pernille J.; Johnson, Mats; Gustafsson, Per; Dahlstrom, Kerstin; Gillberg, Christopher G.; Forssberg, Hans; Westerberg, Helena

2005-01-01

Objective: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic…

Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

Oppositional Defiant Disorder in Adults with ADHD

ERIC Educational Resources Information Center

Reimherr, Frederick W.; Marchant, Barrie K.; Olsen, John L.; Wender, Paul H.; Robison, Reid J.

2013-01-01

Objective: Oppositional defiant disorder (ODD) is the most common comorbid condition in childhood ADHD. This trial was prospectively designed to explore ODD symptoms in ADHD adults. Method: A total of 86 patients in this placebo-controlled, double-blind trial of methylphenidate transdermal system (MTS) were categorized based on the presence of ODD…

[Usage of Calendula officinalis in the prevention and treatment of radiodermatitis: a randomized double-blind controlled clinical trial].

PubMed

Schneider, Franciane; Danski, Mitzy Tannia Reichembach; Vayego, Stela Adami

2015-04-01

To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27) and experimental (24). There is statistically significant evidence (p-value = 0.0120) that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402). Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.

A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers.

PubMed

Jang, Hee-Chang; Kim, Choong Jong; Kim, Kye Hyoung; Lee, Kwang-Hee; Byun, Young-Ho; Seong, Baik-Lin; Saletti, Giulietta; Czerkinsky, Cecil; Park, Wan Beom; Park, Sang-Won; Kim, Hong-Bin; Kim, Nam Joong; Oh, Myoung-don

2010-08-16

A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous "take" reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 99.2% (122/123), and 90.8% (109/120), respectively, and these rates did not differ significantly between the conventional-dose and the low-dose CJ-50300 (1.0x10(8) and 1.0x10(7) plaque-forming units/mL, respectively) (P>0.05 for each). No serious adverse reaction was observed. However, one case of possible generalized vaccinia occurred in the conventionally dosed group [ClinicalTrials.gov Identifier: NCT00607243].

Epilepsy and Neuromodulation—Randomized Controlled Trials

PubMed Central

Kwon, Churl-Su; Ripa, Valeria; Al-Awar, Omar; Panov, Fedor; Ghatan, Saadi; Jetté, Nathalie

2018-01-01

Neuromodulation is a treatment strategy that is increasingly being utilized in those suffering from drug-resistant epilepsy who are not appropriate for resective surgery. The number of double-blinded RCTs demonstrating the efficacy of neurostimulation in persons with epilepsy is increasing. Although reductions in seizure frequency is common in these trials, obtaining seizure freedom is rare. Invasive neuromodulation procedures (DBS, VNS, and RNS) have been approved as therapeutic measures. However, further investigations are necessary to delineate effective targeting, minimize side effects that are related to chronic implantation and to improve the cost effectiveness of these devices. The RCTs of non-invasive modes of neuromodulation whilst showing much promise (tDCS, eTNS, rTMS), require larger powered studies as well as studies that focus at better targeting techniques. We provide a review of double-blinded randomized clinical trials that have been conducted for neuromodulation in epilepsy. PMID:29670050

Inadvertent P-hacking among trials and systematic reviews of the effect of progestogens in pregnancy? A systematic review and meta-analysis.

PubMed

Prior, M; Hibberd, R; Asemota, N; Thornton, J G

2017-06-01

Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking". To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting. Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303. Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews. For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind. Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit. When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective. Progestogens to prevent pregnancy loss, an example of P-hacking. © 2017 Royal College of Obstetricians and Gynaecologists.

The Globalization of Cooperative Groups.

PubMed

Valdivieso, Manuel; Corn, Benjamin W; Dancey, Janet E; Wickerham, D Lawrence; Horvath, L Elise; Perez, Edith A; Urton, Alison; Cronin, Walter M; Field, Erica; Lackey, Evonne; Blanke, Charles D

2015-10-01

The National Cancer Institute (NCI)-supported adult cooperative oncology research groups (now officially Network groups) have a longstanding history of participating in international collaborations throughout the world. Most frequently, the US-based cooperative groups work reciprocally with the Canadian national adult cancer clinical trial group, NCIC CTG (previously the National Cancer Institute of Canada Clinical Trials Group). Thus, Canada is the largest contributor to cooperative groups based in the United States, and vice versa. Although international collaborations have many benefits, they are most frequently utilized to enhance patient accrual to large phase III trials originating in the United States or Canada. Within the cooperative group setting, adequate attention has not been given to the study of cancers that are unique to countries outside the United States and Canada, such as those frequently associated with infections in Latin America, Asia, and Africa. Global collaborations are limited by a number of barriers, some of which are unique to the countries involved, while others are related to financial support and to US policies that restrict drug distribution outside the United States. This article serves to detail the cooperative group experience in international research and describe how international collaboration in cancer clinical trials is a promising and important area that requires greater consideration in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

The Globalization of Cooperative Groups

PubMed Central

Valdivieso, Manuel; Corn, Benjamin W.; Dancey, Janet E.; Wickerham, D. Lawrence; Horvath, L. Elise; Perez, Edith A.; Urton, Alison; Cronin, Walter M.; Field, Erica; Lackey, Evonne; Blanke, Charles D.

2015-01-01

The National Cancer Institute-supported adult cooperative oncology research groups (now officially Network groups) have a long-standing history of participating in international collaborations throughout the world. Most frequently, the U.S. based cooperative groups work reciprocally with the Canadian national adult cancer clinical trial group, NCIC CTG (previously the National Cancer Institute of Canada Clinical Trials Group). Thus, Canada is the largest contributor to cooperative groups based in the U.S., and vice versa. Although international collaborations have many benefits, they are most frequently utilized to enhance patient accrual to large phase III trials originating in the U.S. or Canada. Within the cooperative group setting, adequate attention has not been given to the study of cancers that are unique to countries outside the U.S. and Canada, such as those frequently associated with infections in Latin America, Asia and Africa. Global collaborations are limited by a number of barriers, some of which are unique to the countries involved, while others are related to financial support and to U.S. policies that restrict drug distribution outside the U.S. This manuscript serves to detail the cooperative group experience in international research and describe how international collaboration in cancer clinical trials is a promising and important area that requires greater consideration in the future. PMID:26433551

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial.

PubMed

McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

2002-04-01

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information.

Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.

PubMed

Rambaldi, A; Jacobs, B P; Iaquinto, G; Gluud, C

2005-04-18

Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases. To assess the beneficial and harmful effects of milk thistle or milk thistle constituents versus placebo or no intervention in patients with alcoholic liver disease and/or viral liver diseases (hepatitis B and hepatitis C). The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and full text searches were combined (December 2003). Manufacturers and researchers in the field were contacted. Only randomised clinical trials in patients with alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic) were included. Interventions encompassed milk thistle at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published and no language limitations were applied. The primary outcome measure was mortality. Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality. Thirteen randomised clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered adequately double-blinded. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.

Barriers and facilitators experienced in collaborative prospective research in orthopaedic oncology: A qualitative study.

PubMed

Rendon, J S; Swinton, M; Bernthal, N; Boffano, M; Damron, T; Evaniew, N; Ferguson, P; Galli Serra, M; Hettwer, W; McKay, P; Miller, B; Nystrom, L; Parizzia, W; Schneider, P; Spiguel, A; Vélez, R; Weiss, K; Zumárraga, J P; Ghert, M

2017-05-01

As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration. All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation. The 13 surgeons who participated in the discussion represented orthopaedic oncology practices from seven countries (Argentina, Brazil, Italy, Spain, Denmark, United States and Canada). Four categories and associated themes emerged from the discussion: the need for collaboration in the field of orthopaedic oncology due to the rarity of the tumours and the need for high level evidence to guide treatment; motivational factors for participating in collaborative research including establishing proof of principle, learning opportunity, answering a relevant research question and being part of a collaborative research community; barriers to participation including funding, personal barriers, institutional barriers, trial barriers, and administrative barriers and facilitators for participation including institutional facilitators, leadership, authorship, trial set-up, and the support of centralised study coordination. Orthopaedic surgeons involved in an ongoing international randomised controlled trial (RCT) were motivated by many factors to participate. There were a number of barriers to and facilitators for their participation. There was a collective sense of fatigue experienced in overcoming these barriers, which was mirrored by a strong collective sense of the importance of, and need for, collaborative research in this field. The experiences were described as essential educational first steps to advance collaborative studies in this area. Knowledge gained from this study will inform the development of future large-scale collaborative research projects in orthopaedic oncology. Cite this article: J. S. Rendon, M. Swinton, N. Bernthal, M. Boffano, T. Damron, N. Evaniew, P. Ferguson, M. Galli Serra, W. Hettwer, P. McKay, B. Miller, L. Nystrom, W. Parizzia, P. Schneider, A. Spiguel, R. Vélez, K. Weiss, J. P. Zumárraga, M. Ghert. Barriers and facilitators experienced in collaborative prospective research in orthopaedic oncology: A qualitative study. Bone Joint Res 2017;6:-314. DOI: 10.1302/2046-3758.65.BJR-2016-0192.R1. © 2017 Ghert et al.

Challenges and Successful Pedagogical Strategies: Experiences from Six Swedish Students with Blindness and Autism in Different School Settings.

PubMed

de Verdier, Kim; Fernell, Elisabeth; Ek, Ulla

2018-02-01

The prevalence of autism in children with blindness is much higher than in the general population. There are many challenges regarding the school situation for children with this complex dual disability. This study explored challenges and successful strategies in school for a sample of six Swedish children with blindness and autism, with and without intellectual disability, through qualitative interviews with students, teachers and parents. All students displayed executive functioning deficits, and the teaching situation entailed several challenges. Our research points to the importance of adopting evidence-based practices for ASD, but adapted according to the students lack of vision. For this to be possible, close collaboration between teachers, parents and specialists in the field of visual impairment and autism is necessary.

Maximum type I error rate inflation from sample size reassessment when investigators are blind to treatment labels.

PubMed

Żebrowska, Magdalena; Posch, Martin; Magirr, Dominic

2016-05-30

Consider a parallel group trial for the comparison of an experimental treatment to a control, where the second-stage sample size may depend on the blinded primary endpoint data as well as on additional blinded data from a secondary endpoint. For the setting of normally distributed endpoints, we demonstrate that this may lead to an inflation of the type I error rate if the null hypothesis holds for the primary but not the secondary endpoint. We derive upper bounds for the inflation of the type I error rate, both for trials that employ random allocation and for those that use block randomization. We illustrate the worst-case sample size reassessment rule in a case study. For both randomization strategies, the maximum type I error rate increases with the effect size in the secondary endpoint and the correlation between endpoints. The maximum inflation increases with smaller block sizes if information on the block size is used in the reassessment rule. Based on our findings, we do not question the well-established use of blinded sample size reassessment methods with nuisance parameter estimates computed from the blinded interim data of the primary endpoint. However, we demonstrate that the type I error rate control of these methods relies on the application of specific, binding, pre-planned and fully algorithmic sample size reassessment rules and does not extend to general or unplanned sample size adjustments based on blinded data. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial.

PubMed

Mohammadi, Mohammad-Reza; Kazemi, Mohammad-Reza; Zia, Ebtehal; Rezazadeh, Shams-Ali; Tabrizi, Mina; Akhondzadeh, Shahin

2010-11-01

The aim of the present study was to further evaluate, under double blind and controlled conditions, the efficacy of amantadine for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents as compared to methylphenidate. This was a 6-week randomized clinical trial. Forty patients (28 boys and 12 girls) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial. All study subjects were randomly assigned to receive the treatment using capsule of amantadine at a dose of 100-150 mg/day depending on weight (100 mg/day for <30 kg and 150 mg/day for >30 kg) or methylphenidate at a dose of 20-30 mg/day for a 6-week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV. No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.02; p = 0.86 and df = 1; F = 0.01; p = 0.89, respectively). Side effects of decreased appetite and restlessness were observed more frequently in the methylphenidate group. The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD. Nevertheless, the present results do not constitute proof of efficacy. Copyright © 2010 John Wiley & Sons, Ltd.

Establishing a clinical trials network in nephrology: experience of the Australasian Kidney Trials Network

PubMed Central

Morrish, Alicia T; Hawley, Carmel M; Johnson, David W; Badve, Sunil V; Perkovic, Vlado; Reidlinger, Donna M; Cass, Alan

2014-01-01

Chronic kidney disease is a major public health problem globally. Despite this, there are fewer high-quality, high-impact clinical trials in nephrology than other internal medicine specialties, which has led to large gaps in evidence. To address this deficiency, the Australasian Kidney Trials Network, a Collaborative Research Group, was formed in 2005. Since then, the Network has provided infrastructure and expertise to conduct patient-focused high-quality, investigator-initiated clinical trials in nephrology. The Network has not only been successful in engaging the nephrology community in Australia and New Zealand but also in forming collaborations with leading researchers from other countries. This article describes the establishment, development, and functions of the Network. The article also discusses the current and future funding strategies to ensure uninterrupted conduct of much needed clinical trials in nephrology to improve the outcomes of patients affected by kidney diseases with cost-effective interventions. PMID:24088955

Charles Dickens, trachoma, and blindness in pre-Victorian England.

PubMed

Margo, Curtis E; Harman, Lynn E

In the early 1820s, a Yorkshire boarding school was devastated by an outbreak of blinding ophthalmia. The cause of the epidemic was-in all likelihood-trachoma, then known as Egyptian ophthalmia. The headmaster of the Yorkshire school, William Shaw, was sued for gross negligence by 2 families whose sons went blind during the outbreak. The epidemic and trial would play a role in creating one of the literature's most notorious fictional characters. Eighteen years after the trial, Charles Dickens modeled the vile schoolmaster Wackford Squeers in Nicholas Nickleby after Shaw, whose reputation and career would later be ruined by his thinly disguised portrayal in the novel. The original boarding school epidemic took place while London's first eye hospital was moving to Lower Moorfields, an institution that 17 years earlier was established primarily to cope with Egyptian ophthalmia. We explore trachoma's wide-ranging impact on pre-Victorian England, from inspiring an enduring literary villain to the creation of a renowned eye hospital. Copyright © 2017 Elsevier Inc. All rights reserved.

Corticosteroids for the common cold.

PubMed

Hayward, Gail; Thompson, Matthew J; Perera, Rafael; Del Mar, Chris B; Glasziou, Paul P; Heneghan, Carl J

2015-10-13

The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

Collaborative care for patients with bipolar disorder: a randomised controlled trial

PubMed Central

2011-01-01

Background Bipolar disorder is a severe mental illness with serious consequences for daily living of patients and their caregivers. Care as usual primarily consists of pharmacotherapy and supportive treatment. However, a substantial number of patients show a suboptimal response to treatment and still suffer from frequent episodes, persistent interepisodic symptoms and poor social functioning. Both psychiatric and somatic comorbid disorders are frequent, especially personality disorders, substance abuse, cardiovascular diseases and diabetes. Multidisciplinary collaboration of professionals is needed to combine all expertise in order to achieve high-quality integrated treatment. 'Collaborative Care' is a treatment method that could meet these needs. Several studies have shown promising effects of these integrated treatment programs for patients with bipolar disorder. In this article we describe a research protocol concerning a study on the effects of Collaborative Care for patients with bipolar disorder in the Netherlands. Methods/design The study concerns a two-armed cluster randomised clinical trial to evaluate the effectiveness of Collaborative Care (CC) in comparison with Care as usual (CAU) in outpatient clinics for bipolar disorder or mood disorders in general. Collaborative Care includes individually tailored interventions, aimed at personal goals set by the patient. The patient, his caregiver, the nurse and the psychiatrist all are part of the Collaborative Care team. Elements of the program are: contracting and shared decision making; psycho education; problem solving treatment; systematic relapse prevention; monitoring of outcomes and pharmacotherapy. Nurses coordinate the program. Nurses and psychiatrists in the intervention group will be trained in the intervention. The effects will be measured at baseline, 6 months and 12 months. Primary outcomes are psychosocial functioning, psychiatric symptoms, and quality of life. Caregiver outcomes are burden and satisfaction with care. Discussion Several ways to enhance the quality of this study are described, as well as some limitations caused by the complexities of naturalistic treatment settings where not all influencing factors on an intervention and the outcomes can be controlled. Trial Registration The Netherlands Trial Registry, NTR2600. PMID:21849078

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

PubMed Central

Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

2015-01-01

Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.

PubMed

Gilliaux, Maxime; Renders, Anne; Dispa, Delphine; Holvoet, Dominique; Sapin, Julien; Dehez, Bruno; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan

2015-02-01

Several pilot studies have evoked interest in robot-assisted therapy (RAT) in children with cerebral palsy (CP). To assess the effectiveness of RAT in children with CP through a single-blind randomized controlled trial. Sixteen children with CP were randomized into 2 groups. Eight children performed 5 conventional therapy sessions per week over 8 weeks (control group). Eight children completed 3 conventional therapy sessions and 2 robot-assisted sessions per week over 8 weeks (robotic group). For both groups, each therapy session lasted 45 minutes. Throughout each RAT session, the patient attempted to reach several targets consecutively with the REAPlan. The REAPlan is a distal effector robot that allows for displacements of the upper limb in the horizontal plane. A blinded assessment was performed before and after the intervention with respect to the International Classification of Functioning framework: body structure and function (upper limb kinematics, Box and Block test, Quality of Upper Extremity Skills Test, strength, and spasticity), activities (Abilhand-Kids, Pediatric Evaluation of Disability Inventory), and participation (Life Habits). During each RAT session, patients performed 744 movements on average with the REAPlan. Among the variables assessed, the smoothness of movement (P < .01) and manual dexterity assessed by the Box and Block test (P = .04) improved significantly more in the robotic group than in the control group. This single-blind randomized controlled trial provides the first evidence that RAT is effective in children with CP. Future studies should investigate the long-term effects of this therapy. © The Author(s) 2014.

A double-blind randomized controlled pilot trial examining the safety and efficacy of therapeutic touch in premature infants.

PubMed

Whitley, Julie Anne; Rich, Bonnie L

2008-12-01

To explore the hypothesis that nontouch therapy such as therapeutic touch (TT) reduces stress to a clinically important degree and is safe to use in preterm infants. A pilot randomized, double-blind, controlled trial. Two groups of 10 infants were enrolled and randomly assigned to treatment or nontreatment groups. Gestational age was less than 29 weeks. Demographic descriptions of the 2 groups were statistically similar. The observer and staff were blinded to assignment; the TT practitioner was blinded to observed measurements. Each infant received either TT or no therapeutic touch (NTT) for 5 minutes on 3 consecutive days at the same time of day, behind a curtain. Heart period variability (HPV) was measured 5 minutes before, during, and after the treatment phase. Examination of the parameters of oxygen saturation and episodes of apnea demonstrated no increase in adverse events in TT group compared with NTT group. Repeated-measures multivariate analysis of variance on HPV revealed differences in the interaction of group assignment with low-frequency, high-frequency, and low-to-high- frequency ratio interaction (F2,143 = 8.076, P = .000) and for group, day, and low-frequency, high-frequency, and low-to-high-frequency ratio (F2,288 = 3.146, P = .015), and in the posttreatment time period (F1,16 = 6.259, P = .024), reflective of greater parasympathetic activity in TT group. In this pilot trial, HPV showed an increase for the TT group compared with the NTT group. The study reveals no adverse effects of TT in preterm infants.

Exenatide and the treatment of patients with Parkinson’s disease

PubMed Central

Aviles-Olmos, Iciar; Dickson, John; Kefalopoulou, Zinovia; Djamshidian, Atbin; Ell, Peter; Soderlund, Therese; Whitton, Peter; Wyse, Richard; Isaacs, Tom; Lees, Andrew; Limousin, Patricia; Foltynie, Thomas

2013-01-01

Background. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. Methods. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson’s disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). Results. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). Conclusion. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD. Trial registration. Clinicaltrials.gov NCT01174810. Funding. Cure Parkinson’s Trust. PMID:23728174

Small studies may overestimate the effect sizes in critical care meta-analyses: a meta-epidemiological study

PubMed Central

2013-01-01

Introduction Small-study effects refer to the fact that trials with limited sample sizes are more likely to report larger beneficial effects than large trials. However, this has never been investigated in critical care medicine. Thus, the present study aimed to examine the presence and extent of small-study effects in critical care medicine. Methods Critical care meta-analyses involving randomized controlled trials and reported mortality as an outcome measure were considered eligible for the study. Component trials were classified as large (≥100 patients per arm) and small (<100 patients per arm) according to their sample sizes. Ratio of odds ratio (ROR) was calculated for each meta-analysis and then RORs were combined using a meta-analytic approach. ROR<1 indicated larger beneficial effect in small trials. Small and large trials were compared in methodological qualities including sequence generating, blinding, allocation concealment, intention to treat and sample size calculation. Results A total of 27 critical care meta-analyses involving 317 trials were included. Of them, five meta-analyses showed statistically significant RORs <1, and other meta-analyses did not reach a statistical significance. Overall, the pooled ROR was 0.60 (95% CI: 0.53 to 0.68); the heterogeneity was moderate with an I2 of 50.3% (chi-squared = 52.30; P = 0.002). Large trials showed significantly better reporting quality than small trials in terms of sequence generating, allocation concealment, blinding, intention to treat, sample size calculation and incomplete follow-up data. Conclusions Small trials are more likely to report larger beneficial effects than large trials in critical care medicine, which could be partly explained by the lower methodological quality in small trials. Caution should be practiced in the interpretation of meta-analyses involving small trials. PMID:23302257

PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial.

PubMed

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel; Pedersen, Niels Anker; Dahl, Jørgen Berg; Schrøder, Henrik Morville; Bülow, Hans Henrik; Bjørck, Jan Gottfrid; Overgaard, Søren; Mathiesen, Ole; Wetterslev, Jørn

2017-10-10

Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results. The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively. PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination of paracetamol and ibuprofen used in a perioperative setting. ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015.

The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive–behavioural therapy

PubMed Central

Murphy, Glynis H.; Shepstone, Lee; Wilson, Edward C.F.; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

2016-01-01

Background There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. Aims To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Method Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. Results The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Conclusions Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703772

Implementing Collaborative Learning Methods in the Political Science Classroom

ERIC Educational Resources Information Center

Wolfe, Angela

2012-01-01

Collaborative learning is one, among other, active learning methods, widely acclaimed in higher education. Consequently, instructors in fields that lack pedagogical training often implement new learning methods such as collaborative learning on the basis of trial and error. Moreover, even though the benefits in academic circles are broadly touted,…

Social Support, a Mediator in Collaborative Depression Care for Cancer Patients

ERIC Educational Resources Information Center

Oh, Hyunsung; Ell, Kathleen

2015-01-01

Objective: This study assessed whether perceived social support (PSS) is a factor in improving physical and functional well-being observed among cancer patients receiving collaborative depression care. Methods: A secondary analysis was conducted of data collected in a randomized clinical trial testing the effectiveness of collaborative depression…

The Gluten-Free, Casein-Free Diet in Autism: Results of a Preliminary Double Blind Clinical Trial

ERIC Educational Resources Information Center

Elder, Jennifer Harrison; Shankar, Meena; Shuster, Jonathan; Theriaque, Douglas; Burns, Sylvia; Sherrill, Lindsay

2006-01-01

This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12…

Double-blind evaluation of deanol in tardive dyskinesia.

PubMed

Penovich, P; Morgan, J P; Kerzner, B; Karch, F; Goldblatt, D

1978-05-12

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

ERIC Educational Resources Information Center

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

A Randomized, Rater-Blinded, Parallel Trial of Intensive Speech Therapy in Sub-Acute Post-Stroke Aphasia: The SP-I-R-IT Study

ERIC Educational Resources Information Center

Martins, Isabel Pavao; Leal, Gabriela; Fonseca, Isabel; Farrajota, Luisa; Aguiar, Marta; Fonseca, Jose; Lauterbach, Martin; Goncalves, Luis; Cary, M. Carmo; Ferreira, Joaquim J.; Ferro, Jose M.

2013-01-01

Background: There is conflicting evidence regarding the benefits of intensive speech and language therapy (SLT), particularly because intensity is often confounded with total SLT provided. Aims: A two-centre, randomized, rater-blinded, parallel study was conducted to compare the efficacy of 100 h of SLT in a regular (RT) versus intensive (IT)…

The effectiveness of foot reflexology in inducing ovulation: a sham-controlled randomized trial.

PubMed

Holt, Jane; Lord, Jonathan; Acharya, Umesh; White, Adrian; O'Neill, Nyree; Shaw, Steve; Barton, Andy

2009-06-01

To determine whether foot reflexology, a complementary therapy, has an effect greater than sham reflexology on induction of ovulation. Sham-controlled randomized trial with patients and statistician blinded. Infertility clinic in Plymouth, United Kingdom. Forty-eight women attending the clinic with anovulation. Women were randomized to receive eight sessions of either genuine foot reflexology or sham reflexology with gentle massage over 10 weeks. The primary outcome was ovulation detected by serum progesterone level of >30 nmol/L during the study period. Twenty-six patients were randomized to genuine reflexology and 22 to sham (one randomized patient was withdrawn). Patients remained blinded throughout the trial. The rate of ovulation during true reflexology was 11 out of 26 (42%), and during sham reflexology it was 10 out of 22 (46%). Pregnancy rates were 4 out of 26 in the true group and 2 out of 22 in the control group. Because of recruitment difficulties, the required sample size of 104 women was not achieved. Patient blinding of reflexology studies is feasible. Although this study was too small to reach a definitive conclusion on the specific effect of foot reflexology, the results suggest that any effect on ovulation would not be clinically relevant. Sham reflexology may have a beneficial general effect, which this study was not designed to detect.

The Role of Thoracic Medial Branch Blocks in Managing Chronic Mid and Upper Back Pain: A Randomized, Double-Blind, Active-Control Trial with a 2-Year Followup

PubMed Central

Manchikanti, Laxmaiah; Singh, Vijay; Falco, Frank J. E.; Cash, Kimberly A.; Pampati, Vidyasagar; Fellows, Bert

2012-01-01

Study Design. A randomized, double-blind, active-control trial. Objective. To determine the clinical effectiveness of therapeutic thoracic facet joint nerve blocks with or without steroids in managing chronic mid back and upper back pain. Summary of Background Data. The prevalence of thoracic facet joint pain has been established as 34% to 42%. Multiple therapeutic techniques utilized in managing chronic thoracic pain of facet joint origin include medial branch blocks, radiofrequency neurotomy, and intraarticular injections. Methods. This randomized double-blind active controlled trial was performed in 100 patients with 50 patients in each group who received medial branch blocks with local anesthetic alone or local anesthetic and steroids. Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months. Results. Significant improvement with significant pain relief and functional status improvement of 50% or more were observed in 80% of the patients in Group I and 84% of the patients in Group II at 2-year followup. Conclusions. Therapeutic medial branch blocks of thoracic facets with or without steroids may provide a management option for chronic function-limiting thoracic pain of facet joint origin. PMID:22851967

The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial.

PubMed

Ashida, Ryo; Okamura, Yukiyasu; Wakabayashi-Nakao, Kanako; Mizuno, Takashi; Aoki, Shuichi; Uesaka, Katsuhiko

2018-06-08

To investigate whether preoperative enteral diets -enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized -controlled trial. Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD. © 2018 S. Karger AG, Basel.

Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study.

PubMed

Mohammadi, Mohammad-Reza; Hafezi, Poopak; Galeiha, Ali; Hajiaghaee, Reza; Akhondzadeh, Shahin

2012-01-01

A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg) (group 1) or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for < 30kg and 30 mg/day for > 30kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD) and -15.60±7.81 (mean±SD) for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD) and -22.40±9.90 (mean±SD) for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of buspirone was less effective than methylphenidate in the treatment of ADHD.

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.

Psychological therapy for inpatients receiving acute mental health care: A systematic review and meta-analysis of controlled trials.

PubMed

Paterson, Charlotte; Karatzias, Thanos; Dickson, Adele; Harper, Sean; Dougall, Nadine; Hutton, Paul

2018-04-16

The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta-analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. A systematic review and meta-analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms 'inpatient', 'psychological therapy', and 'acute'. No restriction was placed on diagnosis. The moderating effect of the use of assessor-blind RCT methodology was examined via subgroup and sensitivity analyses. Overall, psychological therapy was associated with small-to-moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow-up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single-blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single-blind RCT methodology was associated with reduced therapy-attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and external validity are now required to establish what type, format, and intensity of brief psychological therapy is required to achieve sustained benefits. Clinical implications: This review provides the first meta-analytical synthesis of brief psychological therapy delivered in acute psychiatric inpatient settings. This review suggests that brief psychological therapy may be associated with reduced emotional distress and readmissions. The evidence in this review is of limited quality. The type, format, and intensity of brief psychological therapy required to achieve sustained benefits are yet to be established. © 2018 The British Psychological Society.

A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery.

PubMed

Bennett-Guerrero, Elliott; Berry, Scott M; Bergese, Sergio D; Fleshner, Phillip R; Minkowitz, Harold S; Segura-Vasi, Alvaro M; Itani, Kamal M F; Henderson, Karen W; Rackowski, Felicia P; Aberle, Laura H; Stryjewski, Martin E; Corey, G Ralph; Allenby, Kent S

2017-06-01

SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Copyright © 2016 Elsevier Inc. All rights reserved.

Implementation of a Novel Adherence Monitoring Strategy in a Phase III, Blinded, Placebo-Controlled, HIV-1 Prevention Clinical Trial.

PubMed

Husnik, Marla J; Brown, Elizabeth R; Marzinke, Mark; Livant, Edward; Palanee-Phillips, Thesla; Hendrix, Craig W; Matovu Kiweewa, Flavia; Nair, Gonasagrie; Soto-Torres, Lydia E; Schwartz, Katie; Hillier, Sharon L; Baeten, Jared M

2017-11-01

Placebo-controlled HIV-1 prevention trials of pre-exposure prophylaxis (PrEP) have not generally used concurrent measurement of adherence because of the potential risk of unblinding. However, several pre-exposure prophylaxis trials for HIV-1 prevention among women failed to show effectiveness because of low product adherence. Evaluation of product adherence objectively during a study provides the opportunity for strengthening adherence activities at sites having low adherence. During MTN-020/ASPIRE, a phase III, placebo-controlled trial of the dapivirine intravaginal ring, we implemented an adherence monitoring system. Monitoring began in quarter 1 (Q1) 2013 and continued through the conclusion of the trial. Blood plasma was collected quarterly and tested for dapivirine concentrations while maintaining blinding among study team members involved in participant management. Dapivirine concentrations >95 pg/mL, reflecting >8 hours of continuous use, were assessed as signaling product use. Study leadership monitored results on a monthly basis and provided feedback to site investigators. Experiences were shared across sites to motivate staff and counsel participants to strive toward higher adherence levels. An upward trend in adherence was observed (P < 0.0001); the proportion of samples from subjects in the active arm with dapivirine >95 pg/mL increased from 63% in Q1 2013 to 84% by Q1 2015. Ongoing drug level testing as a marker of adherence in MTN-020/ASPIRE demonstrates the feasibility of real-time adherence monitoring while maintaining study blinding at the level of participants, sites, and study leadership. This approach is novel for large-scale effectiveness studies for HIV-1 prevention.

Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

PubMed

Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

2013-02-27

This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Wissel, Jörg; Ganapathy, Vaidyanathan; Ward, Anthony B; Borg, Jörgen; Ertzgaard, Per; Herrmann, Christoph; Haggstrom, Anders; Sakel, Mohamed; Ma, Julia; Dimitrova, Rozalina; Fulford-Smith, Antony; Gillard, Patrick

2016-07-01

Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX(®) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain ≥4 achieving ≥30% and ≥50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. At baseline, most patients (74.3%) experienced pain and 47.4% had pain ≥4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P < 0.05). Higher proportions of patients in the pain subgroup achieved ≥30% and ≥50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P < 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials.

PubMed

Thai-Cuarto, Dao; O'Brien, Christopher F; Jimenez, Roland; Liang, Grace S; Burke, Joshua

2018-04-01

Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults. Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication. Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters. The pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8 mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, - 2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment. Results from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.

Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase.

PubMed

Gupta, Ajay; Thompson, David; Whitehouse, Andrew; Collier, Tim; Dahlof, Bjorn; Poulter, Neil; Collins, Rory; Sever, Peter

2017-06-24

In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40-79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest-muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment-and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7-3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2-2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88-1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75-1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56-0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57-1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08-1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10-1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06-1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04-1·88]; p=0·03), which were reported more commonly by statin users than by non-users. These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Pfizer, Servier Research Group, and Leo Laboratories. Copyright © 2017 Elsevier Ltd. All rights reserved.

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).

Transition of patients from blinded study drug to open-label anticoagulation: the ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Mercuri, Michele; Curt, Valentin; Betcher, Joshua; Grip, Laura; Cange, Abby L; Crompton, Andrea E; Murphy, Sabina A; Deenadayalu, Naveen; Antman, Elliott M

2014-08-12

At the end of 2 previous trials, an excess of stroke and bleeding was observed in patients with AF randomized to a new oral anticoagulant (NOAC) who transitioned to a vitamin K antagonist (VKA). The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial compared once-daily edoxaban to warfarin for stroke prevention in patients with AF. An end-of-trial transition plan was developed to minimize the risks of stroke due to inadequate anticoagulation and bleeding from excessive anticoagulation during this critical period. All patients on the blinded study drug at the trial's conclusion were included in this analysis. In pre-specified analyses, stroke, bleeding, and death that occurred through 30 days after the end-of-trial visit were stratified by randomized treatment allocation and open-label anticoagulant selected post-trial. Of the 13,642 patients taking the blinded study drug at the end of the trial, 9,304 (68.2%) were transitioned to open-label VKA and 4,258 patients (31.2%) to an NOAC. There were 21 strokes evenly distributed across the 3 randomized treatment arms: warfarin 7 (1.90%/year), edoxaban high dose 7 (1.89%/year), edoxaban low dose 7 (1.85%/year). Major bleeding was also similar across the 3 treatment arms: warfarin 11 (2.98%/year), edoxaban high dose 10 (2.69%/year), edoxaban low dose 18 (4.76%/year). In patients transitioned to VKA, 85% of patients had at least 1 INR ≥ 2 by day 14 after the transition and 99% by day 30. The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants. (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [EngageAFTIMI48]; NCT00781391). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

Structuring communication relationships for interprofessional teamwork (SCRIPT): a cluster randomized controlled trial

PubMed Central

Zwarenstein, Merrick; Reeves, Scott; Russell, Ann; Kenaszchuk, Chris; Conn, Lesley Gotlib; Miller, Karen-Lee; Lingard, Lorelei; Thorpe, Kevin E

2007-01-01

Background Despite a burgeoning interest in using interprofessional approaches to promote effective collaboration in health care, systematic reviews find scant evidence of benefit. This protocol describes the first cluster randomized controlled trial (RCT) to design and evaluate an intervention intended to improve interprofessional collaborative communication and patient-centred care. Objectives The objective is to evaluate the effects of a four-component, hospital-based staff communication protocol designed to promote collaborative communication between healthcare professionals and enhance patient-centred care. Methods The study is a multi-centre mixed-methods cluster randomized controlled trial involving twenty clinical teaching teams (CTTs) in general internal medicine (GIM) divisions of five Toronto tertiary-care hospitals. CTTs will be randomly assigned either to receive an intervention designed to improve interprofessional collaborative communication, or to continue usual communication practices. Non-participant naturalistic observation, shadowing, and semi-structured, qualitative interviews were conducted to explore existing patterns of interprofessional collaboration in the CTTs, and to support intervention development. Interviews and shadowing will continue during intervention delivery in order to document interactions between the intervention settings and adopters, and changes in interprofessional communication. The primary outcome is the rate of unplanned hospital readmission. Secondary outcomes are length of stay (LOS); adherence to evidence-based prescription drug therapy; patients' satisfaction with care; self-report surveys of CTT staff perceptions of interprofessional collaboration; and frequency of calls to paging devices. Outcomes will be compared on an intention-to-treat basis using adjustment methods appropriate for data from a cluster randomized design. Discussion Pre-intervention qualitative analysis revealed that a substantial amount of interprofessional interaction lacks key core elements of collaborative communication such as self-introduction, description of professional role, and solicitation of other professional perspectives. Incorporating these findings, a four-component intervention was designed with a goal of creating a culture of communication in which the fundamentals of collaboration become a routine part of interprofessional interactions during unstructured work periods on GIM wards. Trial registration Registered with National Institutes of Health as NCT00466297. PMID:17877830

Attention Training in Individuals with Generalized Social Phobia: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Amir, Nader; Beard, Courtney; Taylor, Charles T.; Klumpp, Heide; Elias, Jason; Burns, Michelle; Chen, Xi

2009-01-01

The authors conducted a randomized, double-blind placebo-controlled trial to examine the efficacy of an attention training procedure in reducing symptoms of social anxiety in 44 individuals diagnosed with generalized social phobia (GSP). Attention training comprised a probe detection task in which pictures of faces with either a threatening or…

Statin use and 25-hydroxyvitamin D blood level response to vitamin D treatment of older adults

USDA-ARS?s Scientific Manuscript database

Objectives: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. Design: Pooled analysis. Setting: Three double-blind randomized controlled trials that tested different doses of vitamin D. Participants: Participants of three trials (N = 646; ...

Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

2017-01-01

Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

A Proposed Multisite Double-Blind Randomized Clinical Trial of Neurofeedback for ADHD: Need, Rationale, and Strategy

ERIC Educational Resources Information Center

Kerson, Cynthia

2013-01-01

Objective: Additional treatments with persisting benefit are needed for ADHD. Because ADHD often shows excessive theta electroencephalogram (EEG) power, low beta, and excessive theta-beta ratio (TBR), a promising treatment is neurofeedback (NF) downtraining TBR. Although several nonblind randomized clinical trials (RCTs) show a medium-large…

Towards Defining Adequate Lithium Trials for Individuals with Mental Retardation and Mental Illness.

ERIC Educational Resources Information Center

Pary, Robert J.

1991-01-01

Use of lithium with mentally retarded individuals with psychiatric conditions and/or behavior disturbances is discussed. The paper describes components of an adequate clinical trial and reviews case studies and double-blind cases. The paper concludes that aggression is the best indicator for lithium use, and reviews treatment parameters and…

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study)

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and ...

Training Anxious Children to Disengage Attention from Threat: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Bar-Haim, Yair; Morag, Inbar; Glickman, Shlomit

2011-01-01

Background: Threat-related attention biases have been implicated in the etiology and maintenance of anxiety disorders. As a result, attention bias modification (ABM) protocols have been employed as treatments for anxious adults. However, they have yet to emerge for children. A randomized, double-blind placebo-controlled trial was conducted to…

A Compound Herbal Preparation (CHP) in the Treatment of Children with ADHD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L.

2010-01-01

Objective: Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. Method: Design: A randomized, double-blind, placebo-controlled trial. Setting: University-affiliated tertiary medical center. Participants: 120 children newly diagnosed with ADHD,…

76 FR 23324 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31, rm... Cardiovascular Risk in Diabetes-Lipid (ACCORD Lipid) trial as they relate to the efficacy and safety of the... cholesterol goal. The ACCORD Lipid study was a randomized, double-blind, placebo- controlled add-on trial...

Intervention for Verb Argument Structure in Children with Persistent SLI: A Randomized Control Trial

ERIC Educational Resources Information Center

Ebbels, Susan H.; van der Lely, Heather K. J.; Dockrell, Julie E.

2007-01-01

Purpose: The authors aimed to establish whether 2 theoretically motivated interventions could improve use of verb argument structure in pupils with persistent specific language impairment (SLI). Method: Twenty-seven pupils with SLI (ages 11;0-16;1) participated in this randomized controlled trial with "blind" assessment. Participants were randomly…

Interpretation Training in Individuals with Generalized Social Anxiety Disorder: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Amir, Nader; Taylor, Charles T.

2012-01-01

Objective: To examine the efficacy of a multisession computerized interpretation modification program (IMP) in the treatment of generalized social anxiety disorder (GSAD). Method: The sample comprised 49 individuals meeting diagnostic criteria for GSAD who were enrolled in a randomized, double-blind placebo-controlled trial comparing IMP (n = 23)…

Dietary supplementation with a superoxide dismutase-melon concentrate reduces stress, physical and mental fatigue in healthy people: a randomised, double-blind, placebo-controlled trial.

PubMed

Carillon, Julie; Notin, Claire; Schmitt, Karine; Simoneau, Guy; Lacan, Dominique

2014-06-19

We aimed to investigate effects of superoxide dismutase (SOD)-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32) and placebo (n = 29) for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD) and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. trial approved by the ethical committee of Poitiers (France), and the ClinicalTrials.gov Identifier is NCT01767922.

Use of a medication control officer to reduce bias in a clinical trial: lessons learned from the scleroderma lung study.

PubMed

Hsu, Vivien M; Khanna, Dinesh; Smith, Edwin; Filemon, Tan; Whelton, Sean; Lopata, Mel; Davis, John C; Polito, Albert; Heck, Louis; Molitor, Jerry; Abeles, Micha; Granda, Jose; Korn, Joseph; Clements, Philip

2010-02-01

Scleroderma Lung Study (SLS) was designed to evaluate the efficacy and safety of oral cyclophosphamide (CYC) versus placebo taken for 1 year for scleroderma-associated interstitial lung disease. An independent medication control officer (MCO), usually a physician, at each center was assigned to monitor laboratory and clinical toxicity of study medication and regulate its dosing based on these results. By having an MCO who watched and managed toxicity, the study investigators were free to care for study patients and to assess study outcomes without the potential bias of knowing toxicity data (toxicity from cyclophosphamide is distinctive - cytopenias and hematuria in particular). To assess the usefulness of an MCO, whose chief role was to maintain safety while retaining the blinding in the clinical trial. Patients had safety laboratory testing every 2-4 weeks and results were sent directly to the MCO within 2 days of the test. Other clinical adverse events (AEs) were reported by the patient to a nurse coordinator who reported them to the MCO who then managed the AEs to preserve the blinding of investigators caring for the patients. The MCO was provided pre-determined algorithms for dose adjustments of test medication based on the presence and severity of laboratory abnormalities. Safety monitoring by the MCO was effective in the early detection of drug toxicity with provision of appropriate medical intervention on a timely basis. At the same time, investigator blinding appeared to be maintained. The testing of MCO effectiveness in maintaining blinding and consistency was not defined as an a priori hypothesis and thus complete data relating to the efficacy of the MCO were not collected in a prospective fashion. An MCO and pre-specified monitoring and dosing guidelines, coupled with uniform pre-specified responses to AEs, may be used effectively to preserve investigator blinding and provide consistency in response to AEs in a clinical trial setting, even when AEs of the test medication are distinctive.

Effect of single-dose low-level helium-neon laser irradiation on orthodontic pain: a split-mouth single-blind placebo-controlled randomized clinical trial.

PubMed

Sobouti, Farhad; Khatami, Maziar; Chiniforush, Nasim; Rakhshan, Vahid; Shariati, Mahsa

2015-01-01

Pain is the most common complication of orthodontic treatment. Low-level laser therapy (LLLT) has been suggested as a new analgesic treatment free of the adverse effects of analgesic medications. However, it is not studied thoroughly, and the available studies are quite controversial. Moreover, helium neon (He-Ne) laser has not been assessed before. This split-mouth placebo-controlled randomized clinical trial was performed on 16 male and 14 female orthodontic patients requiring bilateral upper canine retraction. The study was performed at a private clinic in Sari, Iran, in 2014. It was single blind: patients, orthodontist, and personnel were blinded of the allocations, but the laser operator (periodontist) was not blinded. Once canine retractor was activated, a randomly selected maxillary quarter received a single dose of He-Ne laser irradiation (632.8 nm, 10 mw, 6 j/cm(2) density). The other quarter served as the placebo side, treated by the same device but powered off. In the first, second, fourth, and seventh days, blinded patients rated their pain sensed on each side at home using visual analog scale (VAS) questionnaires. There was no harm identified during or after the study. Pain changes were analyzed using two- and one-way repeated-measures ANOVA, Bonferroni, and t-test (α = 0.01, β > 0.99). This trial was not registered. It was self-funded by the authors. Sixteen males and 11 females remained in the study (aged 12-21). Average pain scores sensed in all 4 intervals on control and laser sides were 4.06 ± 2.85 and 2.35 ± 1.77, respectively (t-test P < 0.0001). One-way ANOVA showed significant pain declines over time, in each group (P < 0.0001). Two-way ANOVA showed significant effects for LLLT (P < 0.0001) and time (P = <0.0001). Single-dose He-Ne laser therapy might reduce orthodontic pain caused by retracting maxillary canines.

A Blinded Randomized Controlled Trial of Motivational Interviewing to Improve Adherence with Osteoporosis Medications: Design of the OPTIMA Trial

PubMed Central

Solomon, Daniel H.; Gleeson, Timothy; Iversen, Maura; Avorn, Jerome; Brookhart, M. Alan; Lii, Joyce; Losina, Elena; May, Frank; Patrick, Amanda; Shrank, William H.; Katz, Jeffrey N.

2010-01-01

Purpose While many effective treatments exist for osteoporosis, most people do not adhere to such treatments long-term. No proven interventions exist to improve osteoporosis medication adherence. We report here on the design and initial enrollment in an innovative randomized controlled trial aimed at improving adherence to osteoporosis treatments. Methods The trial represents a collaboration between academic researchers and a state-run pharmacy benefits program for low-income older adults. Beneficiaries beginning treatment with a medication for osteoporosis are targeted for recruitment. We randomize consenting individuals to receive 12-months of mailed education (control arm) or an intervention consisting of one-on-one telephone-based counseling and the mailed education. Motivational Interviewing forms the basis for the counseling program which is delivered by seven trained and supervised health counselors over ten telephone calls. The counseling sessions include scripted dialogue, open-ended questions about medication adherence and its barriers, as well as structured questions. The primary endpoint of the trial is medication adherence measured over the 12-month intervention period. Secondary endpoints include fractures, nursing home admissions, health care resource utilization, and mortality. Results During the first 7 months of recruitment, we have screened 3,638 potentially eligible subjects. After an initial mailing, 1,115 (30.6%) opted out of telephone recruitment and 1,019 (28.0%) could not be successfully contacted. Of the remaining, 879 (24.2%) consented to participate and were randomized. Women comprise over 90% of all groups, mean ages range from 77–80 years old, and the majority in all groups was white. The distribution of osteoporosis medications was comparable across groups and the median number of different prescription drugs used in the prior year was 8–10. Conclusions We have developed a novel intervention for improving osteoporosis medication adherence. The intervention is currently being tested in a large scale randomized controlled trial. If successful, the intervention may represent a useful model for improving adherence to other chronic treatments. PMID:19436935

Effect of caffeine on cycling time-trial performance in the heat.

PubMed

Pitchford, Nathan W; Fell, James W; Leveritt, Michael D; Desbrow, Ben; Shing, Cecilia M

2014-07-01

The purpose of this investigation was to determine whether a moderate dose of caffeine would improve a laboratory simulated cycling time-trial in the heat. Nine well-trained male subjects (VO2max 64.4±6.8mLmin(-1)kg(-1), peak power output 378±40W) completed one familiarisation and two experimental laboratory simulated cycling time-trials in environmental conditions of 35°C and 25% RH 90min after consuming either caffeine (3mgkg(-1) BW) or placebo, in a double blind, cross-over study. Time-trial performance was faster in the caffeine trial compared with the placebo trial (mean±SD, 3806±359s versus 4079±333s, p=0.06, 90%CI 42-500s, 86% likelihood of benefit, d=-0.79). Caffeine ingestion was associated with small to moderate increases in average heart rate (p=0.178, d=0.39), VO2 (p=0.154, d=0.45), respiratory exchange ratio (p=0.292, d=0.35) and core temperature (p=0.616, d=0.22) when compared to placebo, however, these were not statistically significant. Average RPE during the caffeine supplemented time-trial was not significantly different from placebo (p=0.41, d=-0.13). Caffeine supplementation at 3mgkg(-1) BW resulted in a worthwhile improvement in cycling time-trial performance in the heat. Double-blind cross-over study. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Blindness following bleb-related infection in open angle glaucoma.

PubMed

Yamada, Hiroki; Sawada, Akira; Kuwayama, Yasuaki; Yamamoto, Tetsuya

2014-11-01

To estimate the risk of blindness following bleb-related infection after trabeculectomy with mitomycin C in open angle glaucoma, utilizing data obtained from two prospective multicenter studies. The incidence of bleb-related infection in open angle glaucoma after the first or second glaucoma surgery was calculated using a Kaplan-Meier analysis and data from the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS). The rate of blindness following bleb-related infection was calculated using data from the Japan Glaucoma Society Survey of Bleb-related Infection (JGSSBI). Finally, the rate of blindness following bleb-related infection after filtering surgery was estimated based on the above two data sets. Blindness was defined as an eye with a visual acuity of 0.04 or less. The incidences of development of bleb-related infection at 5 years were 2.6 ± 0.7 % (calculated cumulative incidence ± standard error) for all infections and 0.9 ± 0.4 % for endophthalmitis in all cases in the CBIITS data. The rates of blindness in the JGSSBI data were 14 % for the total cases with bleb-related infection and 30 % for the endophthalmitis subgroup. The rate of blindness developing within 5 years following trabeculectomy was estimated to be approximately 0.24-0.36 %. The rate of blindness following bleb-related infection within 5 years after trabeculectomy is considerable and thus careful consideration must be given to the indication for trabeculectomy and the selection of surgical techniques.

The South Asian Origins of the Global Network to Eradicate Blindness: WHO, NGOs, and Decentralization.

PubMed

Williams, Logan D A

2018-03-01

The global network to eradicate blindness emerged out of the work of Western and South Asian professionals to eradicate smallpox which was endemic in South Asia. The history of the emergence of the global network to eradicate blindness demonstrates a shift from vertical command and control public health programs directed by the WHO, to the decentralized public health services originating in non-profit, non-governmental organizations and coordinated by the WHO. The WHO constitution started with a federal regionalist structure that encouraged collaboration and coordination with NGOs. In South Asia in particular, epidemiologists and general medical practitioners moved from eradicating smallpox through the WHO to creating their own domestic and international NGOs based in various countries with a mission to control blindness in South Asia and Africa. In 1975, pushed by the WHO Director General, these new NGOs in turn joined with individual ophthalmologists and existing blind member associations to form the International Agency for the Prevention of Blindness. Thus, the WHO was shaped by, and shaping, international NGOs such as the IAPB. The IAPB pushed for the formation of the WHO Prevention of Blindness program. This was the earliest example of how the IAPB facilitates bottom-up agenda-setting in the WHO. In 1980, when the WHO officially closed the smallpox program, the Prevention of Blindness program first received independent funding. Presently, the IAPB acts as a decentralized arm of the WHO. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of acupuncture on serum metabolic parameters in premenopausal obese women: study protocol for a randomized controlled trial.

PubMed

Kim, Koh-Woon; Yoo, Hye Hyun; Cho, Jae-Heung; Yang, Yo-Chan; Kim, Je-In; Kim, Song-Yi; Park, Ji-Yeun; Park, Hi-Joon; Song, Mi-Yeon

2015-08-04

Complex metabolic changes cause obesity, making weight loss difficult. For this reason, understanding metabolism is important, and considering the shortcomings of conventional treatment options for obesity, acupuncture is a possible option. However, evidence supporting its efficacy on metabolic parameters in obese patients is lacking. The aim of this study is to investigate the effects of acupuncture on serum metabolic parameters in premenopausal obese women. This ongoing study is a randomized, patient-assessor blind, two-arm parallel non-penetrating sham-controlled clinical trial. Eligible participants, premenopausal adult women (19 years of age or older) with a clinical diagnosis of obesity (body mass index of 25 kg/m(2) or more) blinded to the treatment received, will be randomly allocated blindly into the real acupuncture treatment group (manual acupuncture plus electroacupuncture, n = 60) or the sham acupuncture control group (sham acupuncture plus placebo acupuncture without electrical stimulation, n = 60) and receive treatment two times a week for a total of 12 sessions over 6 weeks. The primary outcome measure is the serum cholesterol and triglyceride (TG) levels at baseline and endpoint. The secondary outcomes are body weight, body fat mass, muscle mass, waist and hip circumference, other serum metabolic profiles, International Physical Activity Questionnaire (IPAQ), Social Readjustment Rating Scale (SRRS), Stress Response Inventory (SRI), Fatigue Severity Scale (FSS), the Korean version of the Beck Depression Inventory (BDI), and urine metabolites. Adverse events will be assessed at every visit. The results of this trial (which will be available in 2015) will provide important clinical evidence for the effect of acupuncture on serum metabolites and demonstrate how acupuncture can be helpful for the treatment of obesity. Trial registration registered via US National Institutes of Health Clinical Trials registry (ClinicalTrials.gov) on 11 November 2014, identifier: NCT02066090 .

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

PubMed

Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

Team Leader: Tom Peters--TAP Information Services

ERIC Educational Resources Information Center

Library Journal, 2005

2005-01-01

Tom Peters packs 36 hours of work into the confines of a 24-hour day. Without breaking a sweat, he juggles multiple collaborative projects, which currently include an Illinois academic library shared storage facility; a multistate virtual reference and instruction service for blind and visually impaired individuals (InfoEyes); a virtual meeting…

CCCT - Investigational Drug Steering Committee

Cancer.gov

The Investigational Drug Steering Committee (IDSC) collaborates with NCI in the design and prioritization of early phase drug development trials conducted by the Experimental Therapeutics Clinical Trials Network (ETCTN).

Long-term clinical and cost-effectiveness of collaborative care (versus usual care) for people with mental-physical multimorbidity: cluster-randomised trial.

PubMed

Camacho, Elizabeth M; Davies, Linda M; Hann, Mark; Small, Nicola; Bower, Peter; Chew-Graham, Carolyn; Baguely, Clare; Gask, Linda; Dickens, Chris M; Lovell, Karina; Waheed, Waquas; Gibbons, Chris J; Coventry, Peter

2018-05-15

Collaborative care can support the treatment of depression in people with long-term conditions, but long-term benefits and costs are unknown.AimsTo explore the long-term (24-month) effectiveness and cost-effectiveness of collaborative care in people with mental-physical multimorbidity. A cluster randomised trial compared collaborative care (integrated physical and mental healthcare) with usual care for depression alongside diabetes and/or coronary heart disease. Depression symptoms were measured by the symptom checklist-depression scale (SCL-D13). The economic evaluation was from the perspective of the English National Health Service. 191 participants were allocated to collaborative care and 196 to usual care. At 24 months, the mean SCL-D13 score was 0.27 (95% CI, -0.48 to -0.06) lower in the collaborative care group alongside a gain of 0.14 (95% CI, 0.06-0.21) quality-adjusted life-years (QALYs). The cost per QALY gained was £13 069. In the long term, collaborative care reduces depression and is potentially cost-effective at internationally accepted willingness-to-pay thresholds.Declaration of interestNone.

A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Wigal, Sharon; Swanson, James M.; Feifel, David; Sangal, R. Bart; Elia, Josephine; Casat, Charles D.; Zeldis, Jerome B.; Conners, C. Keith

2004-01-01

Objective: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin[TM]) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). Method: This was a randomized, double-blind study…

Investigator-reported efficacy of azelaic acid foam 15% in patients with papulopustular rosacea: secondary efficacy outcomes from a randomized, controlled, double-blind, phase 3 trial.

PubMed

Solomon, James A; Tyring, Stephen; Staedtler, Gerald; Sand, Meike; Nkulikiyinka, Richard; Shakery, Kaweh

2016-09-01

Papulopustular rosacea (PPR) is characterized by centrofacial papules and pustules commonly associated with erythema. To compare investigator-reported efficacy outcomes for azelaic acid (AzA) foam 15% versus vehicle foam in PPR, a randomized, vehicle-controlled, double-blind phase 3 clinical trial was conducted at 48 US sites. Participants received AzA foam or vehicle foam for 12 weeks. Secondary efficacy outcomes included change in inflammatory lesion count (ILC), therapeutic response rate according to investigator global assessment (IGA), and change in erythema rating. This study was comprised of 961 participants with PPR. The results support the therapeutic superiority of AzA foam over vehicle foam.

Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial

PubMed Central

McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

2002-01-01

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information. PMID:11934908

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform

PubMed Central

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration. PMID:24688591

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform.

PubMed

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration.

Advancing the evidence base in cancer: psychosocial multicenter trials

PubMed Central

2012-01-01

Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

Critical appraisal of clinical trials in multiple system atrophy: Toward better quality.

PubMed

Castro Caldas, Ana; Levin, Johannes; Djaldetti, Ruth; Rascol, Olivier; Wenning, Gregor; Ferreira, Joaquim J

2017-10-01

Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Design and Recruitment for a Randomized Controlled Trial of Problem-Solving Therapy to Prevent Depression among Older Adults with Need for Supportive Services.

PubMed

Albert, Steven M; King, Jennifer; Dew, Mary Amanda; Begley, Amy; Anderson, Stewart; Karp, Jordan; Gildengers, Ari; Butters, Meryl; Reynolds, Charles F

2016-01-01

Addressing subthreshold depression (indicated prevention) and vulnerabilities that increase the risk of major depression or anxiety disorders (selective prevention) is important for protecting mental health in old age. The Depression-Agency Based Collaborative (Dep-ABC) is a prevention trial involving older adults recruited from aging services sites (home care agencies, senior housing, senior centers) who meet criteria for subthreshold depression and disability. Therefore, the authors examine the effectiveness of partnerships with aging services sites for recruiting at-risk older adults, the quality of recruitment and acceptability of the Dep-ABC assessment and intervention, and the baseline status of participants. Dep-ABC is a single-blind randomized controlled prevention trial set in aging services settings but with centralized screening, randomization, in-home assessments, and follow-up. Its intervention arm involves six to eight sessions of problem-solving therapy, in which older adults aged 60+ learn to break down problems that affect well-being and develop strategies to address them. We examined participation rates to assess quality of recruitment across sites and level of disability according to service use. Dep-ABC randomized 104 participants, 68.4% of eligible older adults. Screening using self-reported disability successfully netted a sample in which 74% received home care agency services, with remaining participants similarly impaired in structured self-reports of impairment and on observed performance tests. Direct outreach to aging services providers is an effective way to identify older adults with service needs at high risk of major depression. Problem-solving therapy is acceptable to this population and can be added to current services. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South Africa.

PubMed

Hofmeyr, G J; Gülmezoğlu, A M; Buchmann, E; Howarth, G R; Shaw, A; Nikodem, V C; Cronje, H; de Jager, M; Mahomed, K

1998-03-01

To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labout. Multicentre randomised controlled trial. Four urban academic hospitals in South Africa. Obstetric surveillance included the use of electronic fetal heart rate monitoring in most cases. Women in labour at term with moderate or thick meconium staining of the amniotic fluid. Transcervical amnioinfusion of 800 mL saline at 15 mL per minute, followed by a maintenance infusion at 3 mL per minute. The control group received routine care. Blinding of the intervention was not possible. Caesarean section, meconium aspiration syndrome and perinatal mortality. Caesarean section rates were similar (amnioinfusion group 70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of meconium aspiration syndrome was lower than expected on the basis of previous studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal deaths. There were no significant differences between any of the subsidiary outcomes. This study concurred with three previous trials which found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean section rate, though the pooled data from all identified trials to date show a significant reduction. The findings with respect to meconium aspiration syndrome were inconclusive in this study alone because of the small number of babies affected, but the point estimate of the relative risk was consistent with the finding of a significant reduction in previous studies and with the Zimbabwe arm (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for meconium stained amniotic fluid to reduce the incidence of meconium aspiration syndrome.

Design and Recruitment for a Randomized Controlled Trial of Problem Solving Therapy to Prevent Depression among Older Adults with Need for Supportive Services

PubMed Central

Albert, Steven M.; King, Jennifer; Dew, Mary Amanda; Begley, Amy; Anderson, Stewart; Karp, Jordan; Gildengers, Ari; Butters, Meryl; Reynolds, Charles F.

2015-01-01

Background Addressing subthreshold depression (indicated prevention) as well as vulnerabilities that increase the risk of major depression or anxiety disorders (selective prevention) is important for protecting mental health in old age. The Depression-Agency Based Collaborative is a prevention trial involving older adults recruited from aging services sites (home care agencies, senior housing senior centers) who meet criteria for subthreshold depression and disability. Objective To examine (i) the effectiveness of partnerships with aging services sites for recruiting at-risk older adults, (ii) the quality of recruitment and acceptability of the Dep-ABC assessment and intervention, and (iii) the baseline status of participants. Methods Dep-ABC is a single-blind randomized controlled prevention trial set in aging services settings but with centralized screening, randomization, in-home assessments, and follow-up. Its intervention arm involves 6–8 sessions of problem-solving therapy, in which older adults aged 60+ learn to break down problems that affect wellbeing and develop strategies to address them. We examined participation rates to assess quality of recruitment across sites and level of disability according to service use. Results Dep-ABC randomized 104 participants, 68.4% of eligible older adults. Screening using self-reported disability successfully netted a sample in which 74% received home care agency services, with remaining participants similarly impaired in structured self-reports of impairment and on observed performance tests. Conclusions Direct outreach to aging services providers is an effective way to identify older adults with service needs at high risk of major depression. Problem solving therapy is acceptable to this population and can be added to current services. PMID:26706911

Effectiveness of psychological interventions delivered by non-psychologists on low back pain and disability: a qualitative systematic review.

PubMed

Bostick, Geoff P

2017-11-01

Psychological treatments delivered by non-psychologists have been proposed as a way to increase access to care to address important psychological barriers to recovery in people with low back pain (LBP). This review aimed to synthesize randomized controlled trials (RCTs) that assess the effectiveness of psychological interventions delivered by non-psychologists in reducing pain intensity and disability in adults with LBP, compared with usual care. A systematic review without meta-analysis was carried out. Randomized controlled trials including adult patients with all types of musculoskeletal LBP were eligible. Interventions included those based on psychological principles and delivered by non-psychologists. The primary outcomes of interest were self-reported pain intensity and disability. Information sources included Medline, EMBASE, and the Cochrane Central Registrar for Controlled Trials. The Cochrane Collaboration's tool for assessing risk of bias was used for the evaluation of internal validity. There were 1,101 records identified, 159 were assessed for eligibility, 16 were critically appraised, and 11 studies were included. Mild to moderate risk of bias was present in the included studies, with personnel and patient blinding, treatment fidelity, and attrition being the most common sources of bias. Considerable heterogeneity existed for patient population, intervention components, and comparison groups. Although most studies demonstrated statistical and clinical improvements in pain and disability, few were statistically superior to the comparison group. Consistent with the broader psychological literature, psychological interventions delivered by non-psychologists have modest effects on low back pain and disability. Additional high quality research is needed to understand what patients are likely to respond to psychological interventions, the appropriate dose to achieve the desired outcome, the amount of training required to implement psychological interventions, and the optimal procedures to ensure treatment fidelity. Copyright © 2017 Elsevier Inc. All rights reserved.

Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial

PubMed Central

Tabouret, Emeline; Houillier, Caroline; Martin-Duverneuil, Nadine; Blonski, Marie; Soussain, Carole; Ghesquières, Herve; Houot, Roch; Larrieu, Delphine; Soubeyran, Pierre; Gressin, Remy; Gyan, Emmanuel; Chinot, Olivier; Taillandier, Luc; Choquet, Sylvain; Alentorn, Agusti; Leclercq, Delphine; Omuro, Antonio; Tanguy, Marie-Laure

2017-01-01

Abstract Background. Our aim was to review MRI characteristics of patients with primary CNS lymphoma (PCNSL) enrolled in a randomized phase II trial and to evaluate their potential prognostic value and patterns of relapse, including T2 fluid attenuated inversion recovery (FLAIR) MRI abnormalities. Methods. Neuroimaging findings in 85 patients with PCNSL enrolled in a prospective trial were reviewed blinded to outcomes. MRI characteristics and responses according to International PCNSL Collaborative Group (IPCG) criteria were correlated with progression-free survival (PFS) and overall survival (OS). Results. Multivariate analysis showed that objective response at 2 months (P < .001) and at end of treatment (P = .015) were predictors of prolonged OS. Infratentorial location (P = .008) and large (>11.4 cm3) enhancing tumor volume (P = .006) were associated with poor OS and PFS, respectively. Ratio of change in product of largest diameters at early MRI evaluation but not timing of complete response achievement (early vs delayed) was prognostic for OS. Sixty-nine patients relapsed. Relapse in the brain (n = 52) involved an initial enhancing site, a different site, or both in 46%, 40%, and 14% of patients, respectively. At baseline, non-enhancing T2-FLAIR hypersignal lesions distant from the enhancing tumor site were detected in 18 patients. These lesions markedly decreased (>50%) in 16 patients after chemotherapy, supporting their neoplastic nature. Of these patients, 10/18 relapsed, half (n = 5) in the initially non-enhancing T2-FLAIR lesions. Conclusions. Baseline tumor size and infratentorial localization are of prognostic value in PCNSL. Our findings provide evidence that non-enhancing FLAIR abnormalities may add to overall tumor burden, suggesting that response criteria should be refined to incorporate evaluation of T2-weighted/FLAIR sequences. PMID:27994065

Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial.

PubMed

Goertz, Christine M; Salsbury, Stacie A; Vining, Robert D; Long, Cynthia R; Andresen, Andrew A; Jones, Mark E; Lyons, Kevin J; Hondras, Maria A; Killinger, Lisa Z; Wolinsky, Fredric D; Wallace, Robert B

2013-01-16

Low back pain is a prevalent and debilitating condition that affects the health and quality of life of older adults. Older people often consult primary care physicians about back pain, with many also receiving concurrent care from complementary and alternative medicine providers, most commonly doctors of chiropractic. However, a collaborative model of treatment coordination between these two provider groups has yet to be tested. The primary aim of the Collaborative Care for Older Adults Clinical Trial is to develop and evaluate the clinical effectiveness and feasibility of a patient-centered, collaborative care model with family medicine physicians and doctors of chiropractic for the treatment of low back pain in older adults. This pragmatic, pilot randomized controlled trial will enroll 120 participants, age 65 years or older with subacute or chronic low back pain lasting at least one month, from a community-based sample in the Quad-Cities, Iowa/Illinois, USA. Eligible participants are allocated in a 1:1:1 ratio to receive 12 weeks of medical care, concurrent medical and chiropractic care, or collaborative medical and chiropractic care. Primary outcomes are self-rated back pain and disability. Secondary outcomes include general and functional health status, symptom bothersomeness, expectations for treatment effectiveness and improvement, fear avoidance behaviors, depression, anxiety, satisfaction, medication use and health care utilization. Treatment safety and adverse events also are monitored. Participant-rated outcome measures are collected via self-reported questionnaires and computer-assisted telephone interviews at baseline, and at 4, 8, 12, 24, 36 and 52 weeks post-randomization. Provider-rated expectations for treatment effectiveness and participant improvement also are evaluated. Process outcomes are assessed through qualitative interviews with study participants and research clinicians, chart audits of progress notes and content analysis of clinical trial notes. This pragmatic, pilot randomized controlled trial uses a mixed method approach to evaluate the clinical effectiveness, feasibility, and participant and provider perceptions of collaborative care between medical doctors and doctors of chiropractic in the treatment of older adults with low back pain.

Participatory design of a collaborative clinical trial protocol writing system.

PubMed

Weng, Chunhua; McDonald, David W; Sparks, Dana; McCoy, Jason; Gennari, John H

2007-06-01

To explore concrete approaches to socio-technical design of collaborative healthcare information systems and to design a groupware technology for collaborative clinical trial protocol writing. We conducted "quick and dirty ethnography" through semi-structured interviews, observational studies, and work artifacts analysis to understand the group work for protocol development. We used participatory design through evolutionary prototyping to explore the feature space of a collaborative writing system. Our design strategies include role-based user advocacy, formative evaluation, and change management. Quick and dirty ethnography helped us efficiently understand relevant work practice, and participatory design helped us engage users into design and bring out their tacit work knowledge. Our approach that intertwined both techniques helped achieve a "work-informed and user-oriented" design. This research leads to a collaborative writing system that supports in situ communication, group awareness, and effective work progress tracking. The usability evaluation results have been satisfactory. The system design is being transferred to an organizational tool for daily use.

Exploring medication use by blind patients in Saudi Arabia

PubMed Central

Kentab, Basma Y.; Al-Rowiali, Kholuod Z.; Al-Harbi, Rehab A.; Al-Shammari, Nouf H.; Balhareth, Wiam M.; Al-Yazeed, Huda F.

2014-01-01

Objective To explore the characteristics of medication use and challenges experienced by the blind patients. Methods This cross-sectional descriptive study included blind persons living in Saudi Arabia who were at least 18 years of age. Participants were recruited through a number of nongovernmental blind associations (in the central, western, eastern regions), universities, social networks, and specialized websites for the blind. A questionnaire was designed and administered via face-to-face meetings with participants and made available online through Google Docs. Results There were a total of 121 respondents of which 26 were excluded based on their ability to visually identify their medications or being <18 years old. The majority of the respondents were 18–29 years old (68%), 49% were male and 51% were female. Around 57% had a college degree while 27% had a high school degree. Diagnosis with a chronic disease was reported by 71 participants (79%, 5 missing). The most common diseases were diabetes and asthma (22%) followed by hypertension (17%). Most blind patients (75%) believed that physicians were the most reliable source of medication information. The medication information and services provided by pharmacists were viewed as inadequate by 46%. The most common challenges encountered by blind patients were linked to drug identification (75%), dose recognition (82%), and identification of expiration date (92%). A large number of patients had to rely on persons with normal vision for dispensing and administering the medications. Conclusions Pharmacists can no longer ignore the medication use problems encountered by the blind people. This study may serve as an initial step for planning improvements in pharmaceutical services provided to blind patients. The government, pharmaceutical companies and pharmacists must work in collaboration to address the special needs of the blind. PMID:25685049

A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome.

PubMed

Klupp, Nerida L; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z; Chang, Dennis H

2016-08-11

This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [-0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [-0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705.

A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome

PubMed Central

Klupp, Nerida L.; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z.; Chang, Dennis H.

2016-01-01

This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [−0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [−0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705. PMID:27511742

Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial

PubMed Central

Noehren, Brian; Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol G.T.; Zimmerman, Miriam B.; Crofford, Leslie J.

2015-01-01

Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. Objectives The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. Design This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study. Intervention Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. Measurements The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Limitations Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. Conclusions The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. PMID:25212518

Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial.

PubMed

Noehren, Brian; Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Zimmerman, Miriam B; Crofford, Leslie J; Sluka, Kathleen A

2015-01-01

Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability. To date, there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation (TENS) in the management of pain and improvement in function in individuals with fibromyalgia. The purpose of this study will be to complete a long-term, multicenter study to assess the effects of TENS in women with fibromyalgia. This will be a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial. Three hundred forty-three participants with fibromyalgia will be recruited for this study. Participants will be randomly assigned to 1 of 3 groups: the intervention (TENS), placebo, or no treatment. After completing the randomized period, all participants will receive the intervention for 1 month. The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity. The primary outcome will be pain with movement, with secondary outcomes assessing functional abilities, patient-reported outcomes, and quantitative sensory testing. Because having participants refrain from their typical medications is not practical, their usage and any change in medication use will be recorded. The results of this study will provide some of the first evidence from a large-scale, double-blind, placebo-controlled trial on the effectiveness of TENS on pain control and quality-of-life changes in patients with fibromyalgia. © 2015 American Physical Therapy Association.

Non-steroidal anti-inflammatory drugs for sciatica.

PubMed

Rasmussen-Barr, Eva; Held, Ulrike; Grooten, Wilhelmus Ja; Roelofs, Pepijn Ddm; Koes, Bart W; van Tulder, Maurits W; Wertli, Maria M

2016-10-15

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed drugs for the treatment of sciatica. A previous Cochrane review on the efficacy of NSAIDs summarised findings for acute and chronic low back pain (LBP) and sciatica. This is an update of the original review (2008) focusing on people suffering from sciatica. To determine the efficacy of NSAIDs in pain reduction, overall improvement, and reported side effects in people with sciatica. We performed electronic searches up to 24 June 2015 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PubMed, and two trials registers. We searched reference lists of included studies and relevant reviews on the topics for additional trials. We included randomised controlled trials (double-blind, single-blind, and open-label) that assessed the efficacy of NSAIDs in sciatica. We included all trials that compared NSAIDs to placebo, to other NSAIDs, or to other medication. Additional interventions were allowed if there was a clear contrast for the treatment with NSAIDs in the trial. Three review authors independently assessed the risk of bias and extracted the data. Where feasible we calculated pooled results using Review Manager 5.3. We reported pain relief outcomes using mean difference (MD) with 95% confidence intervals (95% CI). We used risk ratios (RR) with 95% CI to report global improvement of treatment, adverse effects, and additional medication. We performed a meta-analysis if possible. We assessed level of evidence using the GRADE approach. We used standard methodological procedures recommended by The Cochrane Collaboration. We included 10 trials reported in 9 publications (N = 1651). Only one trial out of 10 was assessed at low risk of bias. Five trials used the currently recommended daily dose for the drug, and two trials used lower daily doses available over the counter. Three trials investigated NSAIDs no longer approved for human use. The follow-up duration was short in all studies but one.Three trials (n = 918) compared the effects of NSAIDs to those of placebo on pain reduction. The pooled mean difference showed comparable pain reduction (visual analogue scale, 0 to 100) in the NSAIDs and placebo groups (MD -4.56, 95% CI -11.11 to 1.99). Heterogeneity was high (I 2 = 82%), and the quality of the evidence was very low. When we excluded one trial with a short follow-up of eight hours, the mean difference further decreased (MD -0.09, 95% CI -9.89 to 9.71). Three trials (n = 753) compared NSAIDs to placebo regarding global improvement. We found low-quality evidence that NSAIDs are more effective than placebo with a risk ratio of 1.14 (95% CI 1.03 to 1.27). One trial (n = 214) studied the effect of NSAIDs on disability, finding very low-quality evidence that NSAIDs are no more effective than placebo on disability. Four trials (n = 967) comparing NSAIDs to placebo reported adverse effects, with low-quality evidence that the risk for adverse effects is higher in the NSAID group than in the placebo group (RR 1.40, 95% CI 1.02 to 1.93). The adverse effects reported in this review are consistent with those previously reported in the literature. This updated systematic review including 10 trials evaluating the efficacy of NSAIDs versus placebo or other drugs in people with sciatica reports low- to very low-level evidence using the GRADE criteria. The efficacy of NSAIDs for pain reduction was not significant. NSAIDs showed a better global improvement compared to placebo. These findings must be interpreted with caution, as the level of evidence according to the GRADE classification was very low for the outcome pain reduction and low for global improvement due to small study samples, inconsistent results, imprecision, and a high risk of bias in the included trials. While the trials included in the analysis were not powered to detect potential rare side effects, we found an increased risk for side effects in the short-term NSAIDs use. As NSAIDs are frequently prescribed, the risk-benefit ratio of prescribing the drug needs to be considered.

Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

2014-01-01

The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression. A 2-year randomized, placebo-controlled, double-blind, clinical trial invo...

Inherited Retinal Degenerative Clinical Trial Network

DTIC Science & Technology

2009-10-01

ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

The Effectiveness of Two Grammar Treatment Procedures for Children with SLI: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey

2015-01-01

Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…

A Pilot Controlled Trial of Topiramate for Mania in Children and Adolescents with Bipolar Disorder.

ERIC Educational Resources Information Center

DelBello, Melissa P.; Findling, Robert L.; Kushner, Stuart; Wang, Daniel; Olson, William H.; Capece, Julie A.; Fazzio, Lydia; Rosenthal, Norman R.

2005-01-01

Objective: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type 1. Method: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief…

Venlafaxine ER for the Treatment of Pediatric Subjects with Depression: Results of Two Placebo-Controlled Trials

ERIC Educational Resources Information Center

Emslie, Graham J.; Findling, Robert L.; Yeung, Paul P.; Kunz, Nadia R.; Li, Yunfeng

2007-01-01

Objective: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. Method: Participants received venlafaxine ER (flexible dose,…

Data Mining and Domain Knowledge: An Exploration of Methods to Advance Medical Research

ERIC Educational Resources Information Center

Engle, Kelley M.

2013-01-01

Researchers in the medical domain consider the double-blind placebo controlled clinical trial the gold standard. The data for these clinical trials are collected for a specifically defined hypothesis and there is very little in the realm of secondary data analyses conducted. The underlying purpose of this work is to demonstrate the value and…

Effects of cognitive stimulation therapy Japanese version (CST-J) for people with dementia: a single-blind, controlled clinical trial

PubMed Central

Yamanaka, Katsuo; Kawano, Yoshiyuki; Noguchi, Dai; Nakaaki, Shutaro; Watanabe, Norio; Amano, Takashi; Spector, Aimee

2013-01-01

Objectives Cognitive stimulation therapy (CST) has shown to have significant benefits in improving the cognitive function and quality of life (QOL) in people with mild-to-moderate dementia in a UK randomized controlled trial (RCT). We developed and examined the Japanese version of group CST (CST-J) in a single-blind, controlled clinical trial. Method CST-J consisting of 14 sessions was administered to a treatment group (n = 26) twice a week for 7 weeks. The treatment group was compared with a control group (n = 30). Based on single-blindness, cognition was evaluated by a researcher, and QOL and mood were rated by the participants themselves. Additionally, QOL and mood of participants were rated by care workers who were not blind but who observed them most directly in their daily life (important for social validity). Results A linear mixed model was used for analyses of cognition and QOL. There were significant improvements in cognition [COGNISTAT (Neurobehavioral Cognitive Status Examination) and MMSE (Mini-Mental State Examination)] for the treatment group compared with the control group (p < 0.01). Regarding QOL, the EQ-5D was significant (p = 0.019) and the QoL-AD (Quality of Life – Alzheimer's Disease) showed a positive trend (p = 0.06) when rated by care workers, although not when rated by the participants themselves. Using a nonparametrical analysis, there were significant improvements in the face scale for mood when rated by both the participants (p < 0.01) and the care workers (p = 0.017). Conclusion The CST-J shows promising improvements in cognition, mood, and aspects of QOL for people with dementia in Japanese care settings. A large RCT is now needed. PMID:23550665

[Why multi-national clinical trials now?--Industry perspective].

PubMed

Miki, Satoshi

2007-02-01

Clinical trial environment in Japan has issues such as high clinical development cost, resource-intensive and time-consuming preparation for clinical trial conduct in each clinical site, long "White Space" and slow speed in pt.recruitment. As a result of the Guideline revision in Nov., 2005, overseas' Phase III data is now usable as pivotal data for NDA submissions. Therefore, acceleration of "hollowing out of clinical trails for registration in Japan has been the significant concern. Under such circumstances, the possible solution would be to participate in the Multi-National Clinical Trials." While other Asian countries, EU and the US have rich precedents and experiences in conducting Multi-National Clinical Trials, Japan was left alone and other Asian countries do not need any collaboration with Japan. It is proposed that Japan take initiative to set up the network such as "Asian Clinical Trial Group" and collaborate with other Asian countries from the beginning of early stage development. Eventually, Asia should become the third region to create clinical evidence, same as to EU and the US.

Randomized controlled trial of a health plan-level mood disorders psychosocial intervention for solo or small practices.

PubMed

Kilbourne, Amy M; Nord, Kristina M; Kyle, Julia; Van Poppelen, Celeste; Goodrich, David E; Kim, Hyungjin Myra; Eisenberg, Daniel; Un, Hyong; Bauer, Mark S

2014-01-01

Mood disorders represent the most expensive mental disorders for employer-based commercial health plans. Collaborative care models are effective in treating chronic physical and mental illnesses at little to no net healthcare cost, but to date have primarily been implemented by larger healthcare organizations in facility-based models. The majority of practices providing commercially insured care are far too small to implement such models. Health plan-level collaborative care treatment can address this unmet need. The goal of this study is to implement at the national commercial health plan level a collaborative care model to improve outcomes for persons with mood disorders. A randomized controlled trial of a collaborative care model versus usual care will be conducted among beneficiaries of a large national health plan from across the country seen by primary care or behavioral health practices. At discharge 344 patients identified by health plan claims as hospitalized for unipolar depression or bipolar disorder will be randomized to receive collaborative care (patient phone-based self-management support, care management, and guideline dissemination to practices delivered by a plan-level care manager) or usual care from their provider. Primary outcomes are changes in mood symptoms and mental health-related quality of life at 12 months. Secondary outcomes include rehospitalization, receipt of guideline-concordant care, and work productivity. This study will determine whether a collaborative care model for mood disorders delivered at the national health plan level improves outcomes compared to usual care, and will inform a business case for collaborative care models for these settings that can reach patients wherever they receive treatment. ClinicalTrials.gov Identifier: NCT02041962; registered January 3, 2014.

Multidisciplinary approach to management of maternal asthma (MAMMA [copyright]): the PROTOCOL for a randomized controlled trial.

PubMed

Lim, Angelina; Stewart, Kay; Abramson, Michael J; Walker, Susan P; George, Johnson

2012-12-19

Uncontrolled asthma during pregnancy is associated with the maternal hazards of disease exacerbation, and perinatal hazards including intrauterine growth restriction and preterm birth. Interventions directed at achieving better asthma control during pregnancy should be considered a high priority in order to optimise both maternal and perinatal outcomes. Poor compliance with prescribed asthma medications during pregnancy and suboptimal prescribing patterns to pregnant women have both been shown to be contributing factors that jeopardise asthma control. The aim is to design and evaluate an intervention involving multidisciplinary care for women experiencing asthma in pregnancy. A pilot single-blinded parallel-group randomized controlled trial testing a Multidisciplinary Approach to Management of Maternal Asthma (MAMMA©) which involves education and regular monitoring. Pregnant women with asthma will be recruited from antenatal clinics in Victoria, Australia. Recruited participants, stratified by disease severity, will be allocated to the intervention or the usual care group in a 1:1 ratio. Both groups will be followed prospectively throughout pregnancy and outcomes will be compared between groups at three and six months after recruitment to evaluate the effectiveness of this intervention. Outcome measures include Asthma Control Questionnaire (ACQ) scores, oral corticosteroid use, asthma exacerbations and asthma related hospital admissions, and days off work, preventer to reliever ratio, along with pregnancy and neonatal adverse events at delivery. The use of FEV(1)/FEV(6) will be also investigated during this trial as a marker for asthma control. If successful, this model of care could be widely implemented in clinical practice and justify more funding for support services and resources for these women. This intervention will also promote awareness of the risks of poorly controlled asthma and the need for a collaborative, multidisciplinary approach to asthma management during pregnancy. This is also the first study to investigate the use of FEV1/FEV6 as a marker for asthma control during pregnancy. Australian New Zealand Clinical Trials Registry (ACTRN12612000681853).

Medial Tibial Stress Syndrome: Evidence-Based Prevention

PubMed Central

Craig, Debbie I

2008-01-01

Reference: Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32–40. Clinical Question: Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Data Sources: Studies were identified by searching MEDLINE (1966–2000), Current Contents (1996–2000), Biomedical Collection (1993–1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Study Selection: Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. Data Extraction: A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Main Results: Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. Conclusions: No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury. PMID:18523568

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

PubMed

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-05-05

Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. UMIN000018752. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

PubMed Central

2013-01-01

Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. Trial registration ClinicalTrials.gov Identifier: NCT01579877 PMID:24004451

The Quality of Reporting of Abstracts in Physical Therapy Literature is Suboptimal: Cross-Sectional, Bibliographic Analysis.

PubMed

Richter, Randy R; Sebelski, Chris A; Austin, Tricia M

2016-09-01

The quality of abstract reporting in physical therapy literature is unknown. The purpose of this study was to provide baseline data for judging the future impact of the 2010 Consolidated Standards of Reporting Trials statement specifically referencing the 2008 Consolidated Standards of Reporting Trials statement for reporting of abstracts of randomized controlled trials across and between a broad sample and a core sample of physical therapy literature. A cross-sectional, bibliographic analysis was conducted. Abstracts of randomized controlled trials from 2009 were retrieved from PubMed, PEDro, and CENTRAL. Eligibility was determined using PEDro criteria. For outcomes measures, items from the Consolidated Standards of Reporting Trials statement for abstract reporting were used for assessment. Raters were not blinded to citation details. Using a computer-generated set of random numbers, 150 abstracts from 112 journals comprised the broad sample. A total of 53 abstracts comprised the core sample. Fourteen of 20 Consolidated Standards of Reporting Trials items for both samples were reported in less than 50% of the abstracts. Significantly more abstracts in the core sample reported (% difference core - broad; 95% confidence interval) title (28.4%; 12.9%-41.2%), blinding (15.2%; 1.6%-29.8%), setting (47.6%; 32.4%-59.4%), and confidence intervals (13.1%; 5.0%-25.1%). These findings provide baseline data for determining if continuing efforts to improve abstract reporting are heeded.

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

PubMed

Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

2014-12-01

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained. Copyright © 2014 Elsevier Inc. All rights reserved.

Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

2015-09-15

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration.

PubMed

Dome, Jeffrey S; Graf, Norbert; Geller, James I; Fernandez, Conrad V; Mullen, Elizabeth A; Spreafico, Filippo; Van den Heuvel-Eibrink, Marry; Pritchard-Jones, Kathy

2015-09-20

Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. © 2015 by American Society of Clinical Oncology.

A pilot randomized double-blind placebo-controlled trial on topical chamomile (Matricaria chamomilla L.) oil for severe carpal tunnel syndrome.

PubMed

Hashempur, Mohammad Hashem; Lari, Zeinab Nasiri; Ghoreishi, Parissa Sadat; Daneshfard, Babak; Ghasemi, Mohammad Sadegh; Homayouni, Kaynoosh; Zargaran, Arman

2015-11-01

To assess the effectiveness of standardized topical Chamomile (Matricaria chamomilla L.) oil in patients with severe carpal tunnel syndrome, as a complementary treatment. A pilot randomized double-blind placebo-controlled trial was conducted. Twenty six patients with documented severe carpal tunnel syndrome were treated in two parallel groups with a night splint plus topical chamomile oil or placebo. They were instructed to use their prescribed oil for 4 weeks, twice daily. Symptomatic and functional status of the patients and their electrodiagnostic parameters were evaluated when enrolled and after the trial period, as our outcome measures. A significant improvement of symptomatic and functional status of patients in the chamomile oil group was observed (p = 0.019 and 0.016, respectively) compared with those in the placebo group. However, electrodiagnostic parameters showed no significant changes between the two groups. Chamomile oil improved symptomatic and functional status of patients with severe carpal tunnel syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

A prospective single-blind randomized-controlled trial comparing two surgical techniques for the treatment of snoring: laser palatoplasty versus uvulectomy with punctate palatal diathermy.

PubMed

Uppal, S; Nadig, S; Jones, C; Nicolaides, A R; Coatesworth, A P

2004-06-01

The aim of this study was to compare laser palatoplasty with uvulectomy with punctate palatal diathermy as treatment modalities for snoring. The study design was a prospective, single-blind, randomized-controlled trial. Eighty-three patients entered the trial. After a mean follow-up period of more than 18 months there was no statistically significant difference between the two groups regarding the patient perception of benefit from surgery or the subjective improvement in snoring. However, there was a statistically significant difference in the degree of pain in the immediate postoperative period (mean difference = 22.14, 95% CI = 7.98-36.31, P = 0.003), with the pain being worse in the laser palatoplasty group. Relative risk of complications for laser palatoplasty was 1.42 (95% CI = 0.93-2.17). The snoring scores and Glasgow Benefit Inventory scores decreased with time in both the groups but there was no statistically significant difference between the two groups.

A double-blind trial of ethamsylate in the treatment of primary and intrauterine-device menorrhagia.

PubMed

Harrison, R F; Cambell, S

1976-08-07

22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device (I.U.C.D.) were studied in a double blind trial with crossover of ethamsylate and placebo. Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods, during which patients received ethamsylate ("Dicynene") treatment during two menstrual cycles and placebo during two cycles. During ethamsylate treatment the mean menstrual blood-loss was reduced by 50% in patients with primary menorrhagia and by 19% in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia. Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment. Reported side-effects, which were not serious, were equally common during ethamsylate and placebo treatment.

Mechanism and early intervention research on ALI during emergence surgery of Stanford type-A AAD: Study protocol for a prospective, double-blind, clinical trial.

PubMed

Cheng, Yi; Jin, Mu; Dong, Xiuhua; Sun, Lizhong; Liu, Jing; Wang, Rong; Yang, Yanwei; Lin, Peirong; Hou, Siyu; Ma, Yuehua; Wang, Yuefeng; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

2016-10-01

Stanford type-A acute aortic dissection (AAD) is a severe cardiovascular disease demonstrating the characteristics of acute onset and rapid development, with high morbidity and mortality. The available evidence shows that preoperative acute lung injury (ALI) induced by Stanford type-A AAD is a frequent and important cause for a number of untoward consequences. However, there is no study assessing the incidence of preoperative ALI and its independent determinants before Standford type-A AAD surgery in Chinese adult patients. This is a prospective, double-blind, signal-center clinical trial. We will recruit 130 adult patients undergoing Stanford type-A AAD surgery. The incidence of preoperative ALI will be evaluated. Perioperative clinical baselines and serum variables including coagulation, fibrinolysis, inflammatory, reactive oxygen species, and endothelial cell function will be assayed. The independent factors affecting the occurrence of preoperative ALI will be identified by multiple logistic regression analysis. ClinicalTrials.gov (https://register.clinicaltrials.gov/), Registration number NCT01894334.

The effects of ventilation tubes versus no ventilation tubes for recurrent acute otitis media or chronic otitis media with effusion in 9 to 36 month old Greenlandic children, the SIUTIT trial: study protocol for a randomized controlled trial.

PubMed

Demant, Malene Nøhr; Jensen, Ramon Gordon; Jakobsen, Janus Christian; Gluud, Christian; Homøe, Preben

2017-01-19

The prevalence of otitis media in Greenlandic children is one of the highest in the world. International studies have shown that otitis-prone children may benefit from tubulation of the tympanic membrane. However, it is unknown whether these results can be applied to Greenlandic children and trials on the effects of ventilation tubes in high-risk populations have, to our knowledge, never been conducted. The trial is an investigator-initiated, multicentre, randomized, blinded superiority trial of bilateral ventilation tube insertion versus treatment as usual (no tube) in Greenlandic children aged 9-36 months with chronic otitis media with effusion or recurrent acute otitis media. With randomization stratified by otitis media subtype and trial site, a type 1 error of 5% and a power of 80%, a total of 230 participants are needed to detect a decrease of two visits to a health clinic during 2 years, which is considered the minimal clinical relevant difference. The primary outcome measure will be assessed blindly by investigating medical records. Secondary outcome measures are number of episodes of acute otitis media, quality of life, number of episodes of antibiotics administration and proportion of children with tympanic membrane perforations. This trial will provide evidence-based knowledge of the effects of ventilation tubes in children with middle ear infections from the high-risk Greenlandic population. Furthermore, this trial will improve the understanding of conducting randomized clinical trials in remote areas, where management of logistical aspects is particularly challenging. ClinicalTrials.gov, NCT02490332 . Registered on 14 February 2016.

A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

ERIC Educational Resources Information Center

Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

2009-01-01

A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism

ERIC Educational Resources Information Center

Hyman, Susan L.; Stewart, Patricia A.; Foley, Jennifer; Cain, Usa; Peck, Robin; Morris, Danielle D.; Wang, Hongyue; Smith, Tristram

2016-01-01

To obtain information on the safety and efficacy of the gluten-free/casein-free (GFCF) diet, we placed 14 children with autism, age 3-5 years, on the diet for 4-6 weeks and then conducted a double-blind, placebo-controlled challenge study for 12 weeks while continuing the diet, with a 12-week follow-up. Dietary challenges were delivered via weekly…

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

PubMed

Dellinger, Ryan W; Santos, Santiago Roel; Morris, Mark; Evans, Mal; Alminana, Dan; Guarente, Leonard; Marcotulli, Eric

2017-01-01

NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD +) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD + in whole blood demonstrated that NRPT significantly increases the concentration of NAD + in a dose-dependent manner. NAD + levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD + levels was sustained throughout the entire 8-week trial. NAD + levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD + levels sustainably.

Narcolepsy: current treatment options and future approaches

PubMed Central

Billiard, Michel

2008-01-01

The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

Modafinil for Clozapine-Treated Schizophrenia Patients: A Double-Blind, Placebo-Controlled Pilot Trial

PubMed Central

Freudenreich, Oliver; Henderson, David C.; Macklin, Eric A.; Evins, A. Eden; Fan, Xiaoduo; Cather, Cori; Walsh, Jared P.; Goff, Donald C.

2016-01-01

Background Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning. Objectives To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV–diagnosed schizophrenia patients treated with clozapine. Method A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales. Results Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis. Conclusions Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude. Trial Registration clinicaltrials.gov Identifier: NCT00573417 PMID:19689921

Insufflation with Humidified and Heated Carbon Dioxide in Short-Term Laparoscopy: A Double-Blinded Randomized Controlled Trial

PubMed Central

Herrmann, Anja; De Wilde, Rudy Leon

2015-01-01

Background. We tested the hypothesis that warm-humidified carbon dioxide (CO2) insufflation would reduce postoperative pain and morphine requirement compared to cold-dry CO2 insufflation. Methods. A double-blinded, randomized, controlled trial was conducted to compare warm, humidified CO2 and cold-dry CO2. Patients with benign uterine diseases were randomized to either treatment (n = 48) or control (n = 49) group during laparoscopically assisted vaginal hysterectomy. Primary endpoints of the study were rest pain, movement pain, shoulder-tip pain, and cough pain at 2, 4, 6, 24, and 48 hours postoperatively, measured by visual analogue scale. Secondary outcomes were morphine consumption, rejected boli, temperature change, recovery room stay, and length of hospital stay. Results. There were no significant differences in all baseline characteristics. Shoulder-tip pain at 6 h postoperatively was significantly reduced in the intervention group. Pain at rest, movement pain, and cough pain did not differ. Total morphine consumption and rejected boli at 24 h postoperatively were significantly higher in the control group. Temperature change, recovery room stay, and length of hospital were similar. Conclusions. Warm, humidified insufflation gas significantly reduces postoperative shoulder-tip pain as well as morphine demand. This trial is registered with Clinical Trial Registration Number   DRKS00003853 (German Clinical Trials Register (DRKS)). PMID:25722977

Examining the effectiveness of consuming flour made from agronomically biofortified wheat (Zincol-2016/NR-421) for improving Zn status in women in a low-resource setting in Pakistan: study protocol for a randomised, double-blind, controlled cross-over trial (BiZiFED).

PubMed

Lowe, Nicola M; Khan, Muhammad Jaffar; Broadley, Martin R; Zia, Munir H; McArdle, Harry J; Joy, Edward J M; Ohly, Heather; Shahzad, Babar; Ullah, Ubaid; Kabana, Gul; Medhi, Rashid; Afridi, Mukhtiar Zaman

2018-04-17

Dietary zinc (Zn) deficiency is a global problem, particularly in low-income and middle-income countries where access to rich, animal-source foods of Zn is limited due to poverty. In Pakistan, Zn deficiency affects over 40% of the adult female population, resulting in suboptimal immune status and increased likelihood of complications during pregnancy. We are conducting a double-blind, randomised controlled feeding study with cross-over design in a low-resource setting in Pakistan. Households were provided with flour milled from genetically and agronomically biofortified grain (Zincol-2016/NR-421) or control grain (Galaxy-2013). Fifty households were recruited. Each household included a woman aged 16-49 years who is neither pregnant nor breastfeeding, and not currently consuming nutritional supplements. These women were the primary study participants. All households were provided with control flour for an initial 2-week baseline period, followed by an 8-week intervention period where 25 households receive biofortified flour (group A) and 25 households receive control flour (group B). After this 8-week period, groups A and B crossed over, receiving control and biofortified flour respectively for 8 weeks. Tissue (blood, hair and nails) have been collected from the women at five time points: baseline, middle and end of period 1, and middle and end of period 2. Ethical approval was granted from the lead university (reference no. STEMH 697 FR) and the collaborating institution in Pakistan. The final study methods (including any modifications) will be published in peer-reviewed journals, alongside the study outcomes on completion of the data analysis. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum. The trial has been registered with the ISRCTN registry, study ID ISRCTN83678069. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Conducting non-commercial international clinical trials: the ICR-CTSU experience.

PubMed

Fox, Lisa; Toms, Christy; Kernaghan, Sarah; Snowdon, Claire; Bliss, Judith M

2017-09-26

Academic clinical trials play a fundamental role in the development of new treatments, the repurposing of existing treatments and in addressing areas of unmet clinical need. With cancer treatments increasingly targeted at molecular subtypes, and with priority placed on developing new treatments for rare tumour types, the need for international trial participation to access sufficient patient numbers for successful trial conduct is growing. However, lack of harmonisation of international legal, ethical and financial systems can make this challenging and the cost and effort of conducting trials internationally can be considered prohibitive, particularly where the sample size is comparatively small. The Institute of Cancer Research - Clinical Trials and Statistics Unit (ICR-CTSU) is a UK-based academic clinical trials unit that specialises in the design, conduct and analysis of clinical trials of cancer treatments with an expanding portfolio of trials in molecular subtypes of breast and urological cancers and in other rare cancer types. Implementing appropriate mechanisms to enable international participation has therefore been imperative. In this article, we explain how we have approached the challenges involved and describe examples of successful international trial conduct, achieved through robust collaborations with academic and industry partners. Conducting academic trials internationally is challenging but can and should be achieved through appropriate governance mechanisms and strong collaborations.

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomized controlled trials of vasoactive drugs in acute stroke: The Blood pressure in Acute Stroke Collaboration, stage-3.

PubMed

Sandset, Else Charlotte; Sanossian, Nerses; Woodhouse, Lisa J; Anderson, Craig; Berge, Eivind; Lees, Kennedy R; Potter, John F; Robinson, Thompson G; Sprigg, Nikola; Wardlaw, Joanna M; Bath, Philip M

2018-01-01

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial

PubMed Central

Amrutesh, Sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

2010-01-01

Background The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Objectives Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. Methods One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. Results Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. Conclusion The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it. PMID:27186096

Safety and Tolerability of Panax ginseng Root Extract: A Randomized, Placebo-Controlled, Clinical Trial in Healthy Korean Volunteers

PubMed Central

Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo

2012-01-01

Abstract Objectives Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. Methods This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Results Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. Conclusions P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product. PMID:22909282

Controlled trials in children: quantity, methodological quality and descriptive characteristics of pediatric controlled trials published 1948-2006.

PubMed

Thomson, Denise; Hartling, Lisa; Cohen, Eyal; Vandermeer, Ben; Tjosvold, Lisa; Klassen, Terry P

2010-09-30

The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P<0.0001), as did the proportion of multicentre trials (P = 0.002). Significant increases over time were found in methodological quality (Jadad score) (P<0.0001), the proportion of double-blind studies (P<0.0001), and studies with adequate allocation concealment (P<0.0001). Additionally, we found an improvement in reporting over time: adequate description of withdrawals and losses to follow-up (P<0.0001), sample size calculations (P<0.0001), and intention-to-treat analysis (P<0.0001). However, many trials still do not describe their level of blinding, and allocation concealment was inadequately reported in the majority of studies across the entire time period. The proportion of studies with industry funding decreased slightly over time (P = 0.003), and these studies were more likely to report positive conclusions (P = 0.028). The quantity and quality of pediatric controlled trials has increased over time; however, much work remains to be done, particularly in improving methodological issues around conduct and reporting of trials.

75 FR 28331 - Meaningful Access to United States Currency for Blind and Visually Impaired Persons

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-20

... impaired relating to the identification of U.S. currency through focus groups, surveys, and usability tests.... SUPPLEMENTARY INFORMATION: By statute, the Secretary of the Treasury has sole authority for approving designs of U.S. Federal Reserve notes (U.S. currency). To develop the designs, Treasury works in collaboration...

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

PubMed

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles such as blindness, randomization and control in RCTs, while requiring reporting in accordance with international standards. Copyright© by the Chinese Pharmaceutical Association.

O8.10A MODEL FOR RESEARCH INITIATIVES FOR RARE CANCERS: THE COLLABORATIVE EPENDYMOMA RESEARCH NETWORK (CERN)

PubMed Central

Armstrong, T.S.; Aldape, K.; Gajjar, A.; Haynes, C.; Hirakawa, D.; Gilbertson, R.; Gilbert, M.R.

2014-01-01

Ependymoma represents less than 5% of adult central nervous system (CNS) tumors and a higher percentage of pediatric CNS tumors, but it remains an orphan disease. The majority of the laboratory-based research and clinical trials have been conducted in the pediatric setting, a reflection of the relative incidence and funding opportunities. CERN, created in 2006, was designed to establish a collaborative effort between laboratory and clinical research and pediatric and adult investigators. The organization of CERN is based on integration and collaboration among five projects. Project 1 contains the clinical trials network encompassing both adult and pediatric centers. This group has completed 2 clinical trials with more underway. Project 2 is focused on molecular classification of human ependymoma tumor tissues and also contains the tumor repository which has now collected over 600 fully clinically annotated CNS ependymomas from adults and children. Project 3 is focused on drug discovery utilizing robust laboratory models of ependymoma to perform high throughput screening of drug libraries, then taking promising agents through extensive preclinical testing including monitoring of drug delivery to tumor using state of the art microdialysis. Project 4 contains the basic research efforts evaluating the molecular pathogenesis of ependymoma and has successfully translated these findings by generating the first mouse models of ependymoma that are employed in preclinical drug development in Project 3. Project 5 studies patient outcomes, including the incorporation of these measures in the clinical trials. This project also contains an online Ependymoma Outcomes survey, collecting data on the consequences of the disease and its treatment. These projects have been highly successful and collaborative. For example, the serial measurement of symptom burden (Project 5) has greatly contributed to the evaluation of treatment efficacy of a clinical trial (Project 1) and investigators from Project 2 are evaluating potential predictive markers from tumor tissue from the same clinical trial. Results from genomic and molecular discoveries generated by Project 4 were evaluated using the clinical material from the Tumor Registry (Project 2). Agents identified from the high throughput screening in Project 3 are being used to create novel clinical trials (Project 1). As a complimentary effort, CERN's community outreach efforts provide a major gateway to patients, families, caregivers and healthcare providers, contributing to greater awareness of ependymoma, and supporting clinical trial accrual in Project 1. In summary, CERN has successfully created a collaborative, multi-national integrated effort combining pediatric- and adult-focused investigators spanning from basic science to patient outcomes measures. This research paradigm may be an effective approach for other rare cancers.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

PubMed

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. ClinicalTrials.gov NCT01271933. A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

'We all want to succeed, but we've also got to be realistic about what is happening': an ethnographic study of relationships in trial oversight and their impact.

PubMed

Daykin, Anne; Selman, Lucy E; Cramer, Helen; McCann, Sharon; Shorter, Gillian W; Sydes, Matthew R; Gamble, Carrol; Macefield, Rhiannon; Lane, J Athene; Shaw, Alison

2017-12-22

The oversight and conduct of a randomised controlled trial involves several stakeholders, including a Trial Steering Committee (TSC), Trial Management Group (TMG), Data Monitoring Committee (DMC), funder and sponsor. We aimed to examine how the relationships between these stakeholders affect the trial oversight process and its rigour, to inform future revision of Good Clinical Practice guidelines. Using an ethnographic study design, we observed the oversight processes of eight trials and conducted semi-structured interviews with members of the trials' TSCs and TMGs, plus other relevant informants, including sponsors and funders of trials. Data were analysed thematically, and findings triangulated and integrated to give a multi-perspective account of current oversight practices in the UK. Eight TSC and six TMG meetings from eight trials were observed and audio-recorded, and 66 semi-structured interviews conducted with 52 purposively sampled key informants. Five themes are presented: (1) Collaboration within the TMG and role of the CTU; (2) Collaboration and conflict between oversight committees; (3) Priorities; (4) Communication between trial oversight groups and (5) Power and accountability. There was evidence of collaborative relationships, based on mutual respect, between CTUs, TMGs and TSCs, but also evidence of conflict. Relationships between trial oversight committees were influenced by stakeholders' priorities, both organisational and individual. Good communication following specific, recognised routes played a central role in ensuring that relationships were productive and trial oversight efficient. Participants described the possession of power over trials as a shifting political landscape, and there was lack of clarity regarding the roles and accountability of each committee, the sponsor and funder. Stakeholders' perceptions of their own power over a trial, and the power of others, influenced relationships between those involved in trial oversight. Recent developments in trial design and conduct have been accompanied by changes in roles and relationships between trial oversight groups. Recognising and respecting the value of differing priorities among those involved in running trials is key to successful relationships between committees, funders and sponsors. Clarity regarding appropriate lines of communication, roles and accountability is needed. We present 10 evidence-based recommendations to inform updates to international trial guidance, particularly the Medical Research Council guidelines.

Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG).

PubMed

Escolar, Diana M; Henricson, Erik K; Pasquali, Livia; Gorni, Ksenija; Hoffman, Eric P

2002-10-01

Progress in the development of rationally based therapies for Duchenne muscular dystrophy has been accelerated by encouraging multidisciplinary, multi-institutional collaboration between basic science and clinical investigators in the Cooperative International Research Group. We combined existing research efforts in pathophysiology by a gene expression profiling laboratory with the efforts of animal facilities capable of conducting high-throughput drug screening and toxicity testing to identify safe and effective drug compounds that target different parts of the pathophysiologic cascade in a genome-wide drug discovery approach. Simultaneously, we developed a clinical trial coordinating center and an international network of collaborating physicians and clinics where those drugs could be tested in large-scale clinical trials. We hope that by bringing together investigators at these facilities and providing the infrastructure to support their research, we can rapidly move new bench discoveries through animal model screening and into therapeutic testing in humans in a safe, timely and cost-effective setting.

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

PubMed

Nurnberg, H George; Hensley, Paula L

2003-01-01

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

SMS text messaging as a means of increasing recall of therapy goals in brain injury rehabilitation: a single-blind within-subjects trial.

PubMed

Culley, Campbell; Evans, Jonathan J

2010-01-01

A single-blind within-subjects trial was used to test the efficacy of sending SMS text messages to patients with a traumatic brain injury as a means of improving their recall of rehabilitation goals. Eleven participants were recruited from two community-based rehabilitation centres and were sent text messages relating to three randomly selected goals from a selection of six current goals three times per day for 14 days. Participants' recall of their rehabilitation goals was assessed at baseline, seven days, and 14 days via free recall and cued recall procedures. Results showed that goals in the "text" condition were recalled better than goals in the "no text" condition. Practical applications and extensions are discussed.

Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.

PubMed

Wullt, Marlene; Hagslätt, Marie-Louise Johansson; Odenholt, Inga

2003-01-01

A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.

Effects of a Patient-Provider, Collaborative, Medication-Planning Tool: A Randomized, Controlled Trial

PubMed Central

Wolf, Michael S.; Kaiser, Darren; Morrow, Daniel G.

2016-01-01

Among patients with various levels of health literacy, the effects of collaborative, patient-provider, medication-planning tools on outcomes relevant to self-management are uncertain. Objective. Among adult patients with type II diabetes mellitus, we tested the effectiveness of a medication-planning tool (Medtable™) implemented via an electronic medical record to improve patients' medication knowledge, adherence, and glycemic control compared to usual care. Design. A multicenter, randomized controlled trial in outpatient primary care clinics. 674 patients received either the Medtable tool or usual care and were followed up for up to 12 months. Results. Patients who received Medtable had greater knowledge about indications for medications in their regimens and were more satisfied with the information about their medications. Patients' knowledge of drug indication improved with Medtable regardless of their literacy status. However, Medtable did not improve patients' demonstrated medication use, regimen adherence, or glycemic control (HbA1c). Conclusion. The Medtable tool supported provider/patient collaboration related to medication use, as reflected in patient satisfaction with communication, but had limited impact on patient medication knowledge, adherence, and HbA1c outcomes. This trial is registered with ClinicalTrials.gov NCT01296633. PMID:27699179

Effects of enzyme-potentiated desensitization in the treatment of pollinosis: a double-blind placebo-controlled trial.

PubMed

Astarita, C; Scala, G; Sproviero, S; Franzese, A

1996-01-01

Several controlled clinical trials have shown that specific immunotherapy (SIT) using incremental injections of allergens can be effective in the treatment of allergic rhinitis and asthma. Nevertheless, the risk of side effects have led to some recommended limitations of SIT. Enzyme-potentiated desensitization (EPD) is a proposed method for immunotherapy with very low doses of mixed allergens plus beta-glucuronidase enzyme, for which irrelevant or no side effects have been claimed. The aim of this study was to determine the clinical efficacy of EPD in the treatment of pollinosis. A double-blind placebo-controlled trial of EPD among 20 patients sensitive to Parietaria and grass pollen was performed. All patients recorded daily symptom scores for nine months following a single intradermal injection of EPD or buffered saline received in February. Symptoms recorded were nasal itching and obstruction, sneezing, rhinorrhea, itchy eyes and excessive tear production. Moreover, total and specific lgE were measured and CD3+, CD4+ and CD8+ peripheral blood lymphocytes were counted at different times. In the same period, ten additional subjects, with an allergic clinical profile similar to the subjects admitted to the double-blind trial, were studied in an open clinical trial in order to evaluate the effects of EPD without enzyme using a mixture of allergens. Symptom scores were higher in the placebo group (p < 0.001), with a similar level of significance for both global symptom score and for each individual symptom. Active-treated patients had a significant post-treatment increase in the mean percentage of T-CD8+ peripheral blood cells and a significant post-seasonal decrease in the mean percentage of Parietaria specific lgE. On the contrary, placebo-treated patients had a borderline significant post-seasonal decrease in the mean percentage of CD8+ circulating cells and a significant seasonal increase in the mean percentage of Parietaria specific lgE with no significant post-seasonal decrease. Finally, clinical results of the mixture of allergens injection were similar to those of the placebo in the double-blind trial. EPD injection caused only an asymptomatic, local wheal and flare lasting about two hours. Two patients (20%) in the active-treated group experienced a delayed, mild, unusual headache lasting about two days. In conclusion, EPD is clinically effective in the treatment of pollinosis. Some immunological modifications observed in the EPD-treated patients suggest an EPD-induced enhancement of tolerogenic mechanisms like "immune deviation."

Rehabilitation of cortical blindness secondary to stroke.

PubMed

Gaber, Tarek A-Z K

2010-01-01

Cortical blindness is a rare complication of posterior circulation stroke. However, its complex presentation with sensory, physical, cognitive and behavioural impairments makes it one of the most challenging. Appropriate approach from a rehabilitation standpoint was never reported. Our study aims to discuss the rehabilitation methods and outcomes of a cohort of patients with cortical blindness. The notes of all patients with cortical blindness referred to a local NHS rehabilitation service in the last 6~years were examined. Patients' demographics, presenting symptoms, scan findings, rehabilitation programmes and outcomes were documented. Seven patients presented to our service, six of them were males. The mean age was 63. Patients 1, 2 and 3 had total blindness with severe cognitive and behavioural impairments, wandering and akathisia. All of them failed to respond to any rehabilitation effort and the focus was on damage limitation. Pharmacological interventions had a modest impact on behaviour and sleep pattern. The 3 patients were discharged to a nursing facility. Patients 4, 5, 6 and 7 had partial blindness with variable severity. All of them suffered from significant memory impairment. However, none suffered from any behavioural, physical or other cognitive impairment. Rehabilitation efforts on 3 patients were carried out collaboratively between brain injury occupational therapists and sensory disability officers. All patients experienced significant improvement in handicap and they all maintained community placements. This small cohort of patients suggests that the rehabilitation philosophy and outcomes of these 2 distinct groups of either total or partial cortical blindness differ significantly.

Ophthalmic public health; the way ahead.

PubMed

Heidary, F; Rahimi, A; Gharebaghi, R

2012-01-01

Visual sciences have been progressing quickly in recent decades through globalization phenomenon. An enormous change has taken place in ocular health issues, however, there are various problems facing ophthalmic public health worldwide. In the previous years, the World Health Organization and the International Agency for the Prevention of Blindness in partnership launched the global initiative to eradicate avoidable blindness by the year 2020, VISION 2020 the Right to Sight. It has concentrated on the prevention of blindness disability and recognized a health issue-sight as a human right. In view of challenges ahead of visual sciences, close collaboration between international agencies at the global level to implement new strategies and monitor the progress will be mandatory. In these circumstances non-governmental organizations should not be neglected. World Sight Day 2012 would be a great opportunity to be a focus on importance of visual impairment as an important public health issue and discovering new challenges ahead.

Therapeutic efficacy of traditional Chinese medicine, Shen-Mai San, in cancer patients undergoing chemotherapy or radiotherapy: study protocol for a randomized, double-blind, placebo-controlled trial

PubMed Central

2012-01-01

Background Cancer is one of the major health issues worldwide. An increasing number of cancer patients are offered treatment with surgery, chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) is one of the most common complementary therapies offered to cancer patients in Taiwan. We designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of TCM in patients with cancer. Methods/design In this study, inclusion criteria are postoperative patients with histologically confirmed cancer within 3 years who are undergoing chemotherapy or radiotherapy, more than 18 years old, have given signed informed consent, have the ability to read Chinese, and the ability for oral intake. Exclusion criteria include being pregnant, breast feeding, having completed chemotherapy or radiotherapy, brain metastasis with Eastern Cooperative Oncology Group (ECOG) performance status of two to four, delusion or hallucinations, acute infection, and have received medications under other clinical trials. The patients were separated into an intervention group (Shen-Mai-San, SMS) and a placebo group for four weeks using a randomized, double-blind procedure. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QOL-C30) was used to evaluate the quality of life. General data, hemoglobin (Hb), hematocrit (Hct), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine, carcinoembryonic antigen (CEA), TCM diagnosis data and heart rate variability (HRV) were also recorded. These data were collected at baseline, two weeks and four weeks after receiving medication. The patients were prescribed granules which contained therapeutic medicines or placebo. Paired-T test was used for statistical analysis. Discussion Shen-Mai-San is composed of processed Ginseng radis, Liriope spicata, and Schizandrae fructus. It was found to be effective for treating cancer-related fatigue and had anti-fatigue activity. In TCM theory, SMS has a synergistic effect for qi and yin deficiency and has the ability to prevent fatigue. The symptoms of qi and yin deficiency are similar to chemotherapy- or radiotherapy-induced side effects. In order to evaluate the efficacy of SMS on cancer treatment, we designed a randomized, double-blind, placebo-controlled trial. Trial registration This study is registered to Clinical Trails.gov NCT01580358 PMID:23206440

Structuring Communication Relationships for Interprofessional Teamwork (SCRIPT): a cluster randomized controlled trial.

PubMed

Zwarenstein, Merrick; Reeves, Scott; Russell, Ann; Kenaszchuk, Chris; Conn, Lesley Gotlib; Miller, Karen-Lee; Lingard, Lorelei; Thorpe, Kevin E

2007-09-18

Despite a burgeoning interest in using interprofessional approaches to promote effective collaboration in health care, systematic reviews find scant evidence of benefit. This protocol describes the first cluster randomized controlled trial (RCT) to design and evaluate an intervention intended to improve interprofessional collaborative communication and patient-centred care. The objective is to evaluate the effects of a four-component, hospital-based staff communication protocol designed to promote collaborative communication between healthcare professionals and enhance patient-centred care. The study is a multi-centre mixed-methods cluster randomized controlled trial involving twenty clinical teaching teams (CTTs) in general internal medicine (GIM) divisions of five Toronto tertiary-care hospitals. CTTs will be randomly assigned either to receive an intervention designed to improve interprofessional collaborative communication, or to continue usual communication practices. Non-participant naturalistic observation, shadowing, and semi-structured, qualitative interviews were conducted to explore existing patterns of interprofessional collaboration in the CTTs, and to support intervention development. Interviews and shadowing will continue during intervention delivery in order to document interactions between the intervention settings and adopters, and changes in interprofessional communication. The primary outcome is the rate of unplanned hospital readmission. Secondary outcomes are length of stay (LOS); adherence to evidence-based prescription drug therapy; patients' satisfaction with care; self-report surveys of CTT staff perceptions of interprofessional collaboration; and frequency of calls to paging devices. Outcomes will be compared on an intention-to-treat basis using adjustment methods appropriate for data from a cluster randomized design. Pre-intervention qualitative analysis revealed that a substantial amount of interprofessional interaction lacks key core elements of collaborative communication such as self-introduction, description of professional role, and solicitation of other professional perspectives. Incorporating these findings, a four-component intervention was designed with a goal of creating a culture of communication in which the fundamentals of collaboration become a routine part of interprofessional interactions during unstructured work periods on GIM wards. Registered with National Institutes of Health as NCT00466297.

CCCT - NCTN Steering Committees - Gynecologic Cancers

Cancer.gov

The Gynecologic Cancers Steering Committee evaluates and prioritizes concepts for phase 2 and 3 clinical trials in adult gynecologic cancers. The GCSC is also intent on fostering collaboration with international groups and institutions conducting trials.

Information and Choice of A-Level Subjects: A Cluster Randomised Controlled Trial with Linked Administrative Data

ERIC Educational Resources Information Center

Davies, Peter; Davies, Neil M.; Qiu, Tian

2017-01-01

We estimated the effects of an intervention which provided information about graduate wages to 5593 students in England, using a blinded cluster randomised controlled trial in 50 schools (registration: AEARCTR-0000468). Our primary outcome was students' choice of A-level subjects at age 16. We also recorded the students' expectations of future…

Randomised Controlled Trial of a Parenting Intervention in the Voluntary Sector for Reducing Child Conduct Problems: Outcomes and Mechanisms of Change

ERIC Educational Resources Information Center

Gardner, Frances; Burton, Jennifer; Klimes, Ivana

2006-01-01

Background: To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children. Methods: Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems,…

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Improving the quality of depression and pain care in multiple sclerosis using collaborative care: The MS-care trial protocol.

PubMed

Ehde, Dawn M; Alschuler, Kevin N; Sullivan, Mark D; Molton, Ivan P; Ciol, Marcia A; Bombardier, Charles H; Curran, Mary C; Gertz, Kevin J; Wundes, Annette; Fann, Jesse R

2018-01-01

Evidence-based pharmacological and behavioral interventions are often underutilized or inaccessible to persons with multiple sclerosis (MS) who have chronic pain and/or depression. Collaborative care is an evidence-based patient-centered, integrated, system-level approach to improving the quality and outcomes of depression care. We describe the development of and randomized controlled trial testing a novel intervention, MS Care, which uses a collaborative care model to improve the care of depression and chronic pain in a MS specialty care setting. We describe a 16-week randomized controlled trial comparing the MS Care collaborative care intervention to usual care in an outpatient MS specialty center. Eligible participants with chronic pain of at least moderate intensity (≥3/10) and/or major depressive disorder are randomly assigned to MS Care or usual care. MS Care utilizes a care manager to implement and coordinate guideline-based medical and behavioral treatments with the patient, clinic providers, and pain/depression treatment experts. We will compare outcomes at post-treatment and 6-month follow up. We hypothesize that participants randomly assigned to MS Care will demonstrate significantly greater control of both pain and depression at post-treatment (primary endpoint) relative to those assigned to usual care. Secondary analyses will examine quality of care, patient satisfaction, adherence to MS care, and quality of life. Study findings will aid patients, clinicians, healthcare system leaders, and policy makers in making decisions about effective care for pain and depression in MS healthcare systems. (PCORI- IH-1304-6379; clinicaltrials.gov: NCT02137044). This trial is registered at ClinicalTrials.gov, protocol NCT02137044. Copyright © 2017 Elsevier Inc. All rights reserved.

Reconciling research and community priorities in participatory trials: application to Padres Informados/Jovenes Preparados.

PubMed

Allen, Michele L; Garcia-Huidobro, Diego; Bastian, Tiana; Hurtado, G Ali; Linares, Roxana; Svetaz, María Veronica

2017-06-01

Participatory research (PR) trials aim to achieve the dual, and at times competing, demands of producing an intervention and research process that address community perspectives and priorities, while establishing intervention effectiveness. To identify research and community priorities that must be reconciled in the areas of collaborative processes, study design and aim and study implementation quality in order to successfully conduct a participatory trial. We describe how this reconciliation was approached in the smoking prevention participatory trial Padres Informados/Jovenes Preparados (Informed Parents/Prepared Youth) and evaluate the success of our reconciled priorities. Data sources to evaluate success of the reconciliations included a survey of all partners regarding collaborative group processes, intervention participant recruitment and attendance and surveys of enrolled study participants assessing intervention outcomes. While we successfully achieved our reconciled collaborative processes and implementation quality goals, we did not achieve our reconciled goals in study aim and design. Due in part to the randomized wait-list control group design chosen in the reconciliation process, we were not able to demonstrate overall efficacy of the intervention or offer timely services to families in need of support. Achieving the goals of participatory trials is challenging but may yield community and research benefits. Innovative research designs are needed to better support the complex goals of participatory trials. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Collaborative Evaluation of a High School Prevention Curriculum: How Methods of Collaborative Evaluation Enhanced a Randomized Control Trial to Inform Program Improvement

ERIC Educational Resources Information Center

Orsini, Muhsin Michael; Wyrick, David L.; Milroy, Jeffrey J.

2012-01-01

Blending high-quality and rigorous research with pure evaluation practice can often be best accomplished through thoughtful collaboration. The evaluation of a high school drug prevention program (All Stars Senior) is an example of how perceived competing purposes and methodologies can coexist to investigate formative and summative outcome…

A trial map and GIS class on junior high school with university collaboration in Yokohama, Japan

NASA Astrophysics Data System (ADS)

Tabe, Toshimitsu; Ohnishi, Koji

2018-05-01

On the new curriculum of high school in Japan, geography will be compulsory subject in Japan from 2022. The indexes of new high school geography as compulsory subject will be 1. Using of maps and GIS, 2. Understanding of the world and International collaboration: Life and culture, issues of world, 3. Disaster prevention and ESD: natural environment and disaster, and construction of ideal society. The instruction of the GIS will be one of the issues for social studies teachers in the new curriculum. The aim of this study is to make the utilize map and GIS education content through trial class in junior high school. Trial class was done on Tsurugamine junior high school in Yokohama city with university and Yokohama city school board collaboration. In the trial class, the teacher indicated the old and new topographical maps to students and asked them to consider the characteristics of the area and the land use change. Transparent sheets overlaying is useful this activity. Transparent usage indicated the GIS function of overlay. It is good activity for students to understand the function of GIS. After the considering land use changes, they considered the future of their town. The several unused lands are spread in this area. Students present their opinions how to develop them. The important thing to carry out map and GIS class through neighborhood area is preparation of adequate maps. For this preparation, collaboration with university geography stuffs or undergraduate students are effective.

Further statistics in dentistry. Part 4: Clinical trials 2.

PubMed

Petrie, A; Bulman, J S; Osborn, J F

2002-11-23

The principles which underlie a well-designed clinical trial were introduced in a previous paper. The trial should be controlled (to ensure that the appropriate comparisons are made), randomised (to avoid allocation bias) and, preferably, blinded (to obviate assessment bias). However, taken in isolation, these concepts will not necessarily ensure that meaningful conclusions can be drawn from the study. It is essential that the sample size is large enough to enable the effects of interest to be estimated precisely, and to detect any real treatment differences.

Turmeric

MedlinePlus

... irritation that often occurs after radiation treatments for breast cancer. Other preliminary studies in people have looked at ... double-blind, placebo-controlled clinical trial of thirty breast cancer patients . Radiation Research. 2013;180(1):34-43. ...

Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.

PubMed

Danese, Silvio; Fiorino, Gionata; Peyrin-Biroulet, Laurent; Lucenteforte, Ersilia; Virgili, Gianni; Moja, Lorenzo; Bonovas, Stefanos

2014-05-20

Biological agents are emerging treatment options for the management of ulcerative colitis (UC). To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents. MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites. Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC. Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias. There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo. Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials. Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

Why all randomised controlled trials produce biased results.

PubMed

Krauss, Alexander

2018-06-01

Randomised controlled trials (RCTs) are commonly viewed as the best research method to inform public health and social policy. Usually they are thought of as providing the most rigorous evidence of a treatment's effectiveness without strong assumptions, biases and limitations. This is the first study to examine that hypothesis by assessing the 10 most cited RCT studies worldwide. These 10 RCT studies with the highest number of citations in any journal (up to June 2016) were identified by searching Scopus (the largest database of peer-reviewed journals). This study shows that these world-leading RCTs that have influenced policy produce biased results by illustrating that participants' background traits that affect outcomes are often poorly distributed between trial groups, that the trials often neglect alternative factors contributing to their main reported outcome and, among many other issues, that the trials are often only partially blinded or unblinded. The study here also identifies a number of novel and important assumptions, biases and limitations not yet thoroughly discussed in existing studies that arise when designing, implementing and analysing trials. Researchers and policymakers need to become better aware of the broader set of assumptions, biases and limitations in trials. Journals need to also begin requiring researchers to outline them in their studies. We need to furthermore better use RCTs together with other research methods. Key messages RCTs face a range of strong assumptions, biases and limitations that have not yet all been thoroughly discussed in the literature. This study assesses the 10 most cited RCTs worldwide and shows that trials inevitably produce bias. Trials involve complex processes - from randomising, blinding and controlling, to implementing treatments, monitoring participants etc. - that require many decisions and steps at different levels that bring their own assumptions and degree of bias to results.

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

PubMed Central

2012-01-01

Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. Conclusion This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. Trial registration Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au) ACTRN12611000092998 PMID:23241329

[Principles of controlled clinical trials].

PubMed

Martini, P

1962-01-01

The recovery of the patient should be facilitated as the result of therapeutic research. The basic rule for every therapeutic-clinical trial mist involve a comparison of therapeutic approaches. In acute conditions, such as acute infectious diseases, infarcts, etc., comparisons should be made between two or more groups: the collective therapeutic comparison = the between patients trial. The formation of groups, to be compared one with the other can be justified only if one is reasonably sure that a pathogenic condition indeed exists. In chronic diseases, which extend essentially unchanged over a lengthy period but are nevertheless reversible, therapeutic comparisons may be made between two or more time intervals within the course of the disease in the same individual. This type of therapeutic trial rests primarily upon a (refined!) type of specious reasoning and secondarily, upon modified statistics: the individual therapeutic comparison = the within patient trial. The collective therapeutic comparison, on the one hand, and the individual therapeutic comparison on the other, overlap somewhat in scope. The immediate therapeutic effect is not always an indication of its true value, which may become evident only upon long-term treatment. The short-term trials of therapeutic regimens in an individual must, therefore, be frequently supplemented by long-term trials which can only be carried out by comparing two groups. For many clinical investigations, therefore, the joint efforts of numerous hospitals are absolutely necessary. The second basic rule of therapeutic research is the elimination of secondary causes. The difficulties introduced by these secondary considerations are far greater in therapeutic trials carried out on ambulatory patients than has been hitherto realized. In order to remove subjective secondary causes, the author demanded, in 1931, the use of hidden or illusory media (placebos, dummies) that is, unconscious causative agents. The double blind procedure is indispensible in all experiments, especially where psychological processes and problems are of foremost importance. Therefore, it is absolutely necessary that convincing tests be finally carried out with the double blind procedure on the one hand, and the simple blind procedure on the other in order to determine the range and limitations of both. Therapeutic research of the future is threatened by the hazard of self-satisfaction which produces a sense of accomplishment merely as the result of obeying formal conditions and of following formal standards of accuracy.

Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.

PubMed

Bhat, Amritha; Grote, Nancy K; Russo, Joan; Lohr, Mary Jane; Jung, Hyunzee; Rouse, Caroline E; Howell, Elaine C; Melville, Jennifer L; Carson, Kathy; Katon, Wayne

2017-01-01

The study examined the effectiveness of a perinatal collaborative care intervention in moderating the effects of adverse neonatal birth events on risks of postpartum depressive symptoms and impaired functioning among women of lower socioeconomic status with antenatal depression. A randomized controlled trial with blinded outcome assessments was conducted in ten public health centers, comparing MOMCare (choice of brief interpersonal psychotherapy, pharmacotherapy, or both) with intensive maternity support services (MSS-Plus). Participants had probable diagnoses of major depressive disorder or dysthymia during pregnancy. Generalized estimating equations estimated differences in depression and functioning measures between groups with and without adverse birth events within the treatment arms. A total of 160 women, 43% of whom experienced at least one adverse birth event, were included in the analyses. For women who received MOMCare, postpartum depression scores (measured with the Symptom Checklist-20) did not differ by whether or not they experienced an adverse birth event (mean±SD scores of .86±.51 for mothers with an adverse birth event and .83±.56 for mothers with no event; p=.78). For women who received MSS-Plus, having an adverse birth event was associated with persisting depression in the postpartum period (mean scores of 1.20±.0.61 for mothers with an adverse birth event and .93±.52 for mothers without adverse birth event; p=.04). Similar results were seen for depression response rates and functioning. MOMCare mitigated the risk of postpartum depressive symptoms and impaired functioning among women of low socioeconomic status who had antenatal depression and who experienced adverse birth events.

AVERT2 (a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff.

PubMed

Bernhardt, Julie; Lindley, Richard I; Lalor, Erin; Ellery, Fiona; Chamberlain, Jan; Van Holsteyn, John; Collier, Janice M; Dewey, Helen M; Parsons, Brooke; Moodie, Marjory; Lennon, Sheila; Donnan, Geoffrey A; Thrift, Amanda G; Churilov, Leonid; Langhorne, Peter

2015-12-11

To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Retrospective observational analysis. 56 acute stroke hospitals in eight countries. 1074 trial physiotherapists, nurses, and other clinicians. Number of babies born during trial recruitment per trial participant recruited. With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators' meetings and helped maintain a cohesive collaborative group. Australian New Zealand Clinical Trials Registry no 12606000185561. Participation in a rehabilitation trial does not guarantee successful reproductive activity. 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.

Redesigning a large school-based clinical trial in response to changes in community practice

PubMed Central

Gerald, Lynn B; Gerald, Joe K; McClure, Leslie A; Harrington, Kathy; Erwin, Sue; Bailey, William C

2011-01-01

Background Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. Purpose To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. Methods The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer’s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. Results The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. Limitations The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. Conclusions The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices. PMID:21730079

Redesigning a large school-based clinical trial in response to changes in community practice.

PubMed

Gerald, Lynn B; Gerald, Joe K; McClure, Leslie A; Harrington, Kathy; Erwin, Sue; Bailey, William C

2011-06-01

Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer's active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.

Critical appraisal of fundamental items in approved clinical trial research proposals in Mashhad University of Medical Sciences

PubMed Central

Shakeri, Mohammad-Taghi; Taghipour, Ali; Sadeghi, Masoumeh; Nezami, Hossein; Amirabadizadeh, Ali-Reza; Bonakchi, Hossein

2017-01-01

Background: Writing, designing, and conducting a clinical trial research proposal has an important role in achieving valid and reliable findings. Thus, this study aimed at critically appraising fundamental information in approved clinical trial research proposals in Mashhad University of Medical Sciences (MUMS) from 2008 to 2014. Methods: This cross-sectional study was conducted on all 935 approved clinical trial research proposals in MUMS from 2008 to 2014. A valid and reliable as well as comprehensive, simple, and usable checklist in sessions with biostatisticians and methodologists, consisting of 11 main items as research tool, were used. Agreement rate between the reviewers of the proposals, who were responsible for data collection, was assessed during 3 sessions, and Kappa statistics was calculated at the last session as 97%. Results: More than 60% of the research proposals had a methodologist consultant, moreover, type of study or study design had been specified in almost all of them (98%). Appropriateness of study aims with hypotheses was not observed in a significant number of research proposals (585 proposals, 62.6%). The required sample size for 66.8% of the approved proposals was based on a sample size formula; however, in 25% of the proposals, sample size formula was not in accordance with the study design. Data collection tool was not selected appropriately in 55.2% of the approved research proposals. Type and method of randomization were unknown in 21% of the proposals and dealing with missing data had not been described in most of them (98%). Inclusion and exclusion criteria were (92%) fully and adequately explained. Moreover, 44% and 31% of the research proposals were moderate and weak in rank, respectively, with respect to the correctness of the statistical analysis methods. Conclusion: Findings of the present study revealed that a large portion of the approved proposals were highly biased or ambiguous with respect to randomization, blinding, dealing with missing data, data collection tool, sampling methods, and statistical analysis. Thus, it is essential to consult and collaborate with a methodologist in all parts of a proposal to control the possible and specific biases in clinical trials. PMID:29445703

Critical appraisal of fundamental items in approved clinical trial research proposals in Mashhad University of Medical Sciences.

PubMed

Shakeri, Mohammad-Taghi; Taghipour, Ali; Sadeghi, Masoumeh; Nezami, Hossein; Amirabadizadeh, Ali-Reza; Bonakchi, Hossein

2017-01-01

Background: Writing, designing, and conducting a clinical trial research proposal has an important role in achieving valid and reliable findings. Thus, this study aimed at critically appraising fundamental information in approved clinical trial research proposals in Mashhad University of Medical Sciences (MUMS) from 2008 to 2014. Methods: This cross-sectional study was conducted on all 935 approved clinical trial research proposals in MUMS from 2008 to 2014. A valid and reliable as well as comprehensive, simple, and usable checklist in sessions with biostatisticians and methodologists, consisting of 11 main items as research tool, were used. Agreement rate between the reviewers of the proposals, who were responsible for data collection, was assessed during 3 sessions, and Kappa statistics was calculated at the last session as 97%. Results: More than 60% of the research proposals had a methodologist consultant, moreover, type of study or study design had been specified in almost all of them (98%). Appropriateness of study aims with hypotheses was not observed in a significant number of research proposals (585 proposals, 62.6%). The required sample size for 66.8% of the approved proposals was based on a sample size formula; however, in 25% of the proposals, sample size formula was not in accordance with the study design. Data collection tool was not selected appropriately in 55.2% of the approved research proposals. Type and method of randomization were unknown in 21% of the proposals and dealing with missing data had not been described in most of them (98%). Inclusion and exclusion criteria were (92%) fully and adequately explained. Moreover, 44% and 31% of the research proposals were moderate and weak in rank, respectively, with respect to the correctness of the statistical analysis methods. Conclusion: Findings of the present study revealed that a large portion of the approved proposals were highly biased or ambiguous with respect to randomization, blinding, dealing with missing data, data collection tool, sampling methods, and statistical analysis. Thus, it is essential to consult and collaborate with a methodologist in all parts of a proposal to control the possible and specific biases in clinical trials.

Whole body vibration exercise for chronic low back pain: study protocol for a single-blind randomized controlled trial.

PubMed

Wang, Xue-Qiang; Pi, Yan-Lin; Chen, Pei-Jie; Chen, Bin-Lin; Liang, Lei-Chao; Li, Xin; Wang, Xiao; Zhang, Juan

2014-04-02

Low back pain affects approximately 80% of people at some stage in their lives. Exercise therapy is the most widely used nonsurgical intervention for low back pain in practice guidelines. Whole body vibration exercise is becoming increasingly popular for relieving musculoskeletal pain and improving health-related quality of life. However, the efficacy of whole body vibration exercise for low back pain is not without dispute. This study aims to estimate the effect of whole body vibration exercise for chronic low back pain. We will conduct a prospective, single-blind, randomized controlled trial of 120 patients with chronic low back pain. Patients will be randomly assigned into an intervention group and a control group. The intervention group will participate in whole body vibration exercise twice a week for 3 months. The control group will receive general exercise twice a week for 3 months. Primary outcome measures will be the visual analog scale for pain, the Oswestry Disability Index and adverse events. The secondary outcome measures will include muscle strength and endurance of spine, trunk proprioception, transversus abdominis activation capacity, and quality of life. We will conduct intention-to-treat analysis if any participants withdraw from the trial. Important features of this study include the randomization procedures, single-blind, large sample size, and a standardized protocol for whole body vibration in chronic low back pain. This study aims to determine whether whole body vibration exercise produces more beneficial effects than general exercise for chronic low back pain. Therefore, our results will be useful for patients with chronic low back pain as well as for medical staff and health-care decision makers. Chinese Clinical Trial Registry: ChiCTR-TRC-13003708.

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

PubMed

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-06-01

To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-term effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme (a double-blind placebo-controlled study) - rationale for the study design.

PubMed

Szlagatys-Sidorkiewicz, Agnieszka; Brzeziński, Michał; Jankowska, Agnieszka; Metelska, Paulina; Słomińska-Frączek, Magdalena; Socha, Piotr

2017-04-04

Obesity is associated not only with an array of metabolic disorders (e.g. insulin resistance, hiperinsulinemia, impaired tolerance of glucose, lipid disorders) but also skeletal and joint abnormalities. Recently, a pleiotropic role of vitamin D has been emphasized. Obese children frequently present with vitamin D deficiency, and greater fat mass is associated with lower serum concentration of this vitamin. Although some evidence suggests that weight loss may affect vitamin D status, this issue has not been studied extensively thus far. The aim of a double-blind placebo-controlled study is to assess long-term health effects of vitamin D supplementation in vitamin D deficient obese children participating in an integrated weight-loss programme. A randomized double-blind, placebo-controlled trial analysing the effects of vitamin D3 supplementation in overweight or obese vitamin D deficient (<30 ng/ml) children participating in an integrated weight-loss programme. Children are randomized to receive either vitamin D (1200 IU) or placebo for 26 weeks. Primary endpoints include changes in BMI (body mass index), body composition and bone mineral density at the end of the study period, and secondary endpoints - the changes in laboratory parameter reflecting liver and kidney function (transaminases, creatinine) and glucose homeostasis (glucose and insulin levels during oral glucose tolerance test). The effects of vitamin D supplementation in obese individuals, especially children, subjected to a weight-loss program are still poorly understood. Considering physiological processes associated with puberty and adolescent growth, we speculate that supplementation may enhance weight reduction and prevent bone loss in obese children deficient in this vitamin. NCT 02828228 ; Trial registration date: 8 Jun 2016; Registered in: ClinicalTrials.gov. The trial was registered retrospectively.

Feasibility of a Trial on Improvisational Music Therapy for Children with Autism Spectrum Disorder.

PubMed

Geretsegger, Monika; Holck, Ulla; Bieleninik, Łucja; Gold, Christian

2016-01-01

To conduct generalizable, rigorously designed, adequately powered trials investigating music therapy and other complex interventions, it is essential that study procedures are feasible and acceptable for participants. To date, only limited evidence on feasibility of trial designs and strategies to facilitate study implementation is available in the music therapy literature. Using data from a subsample of a multi-center RCT on improvisational music therapy (IMT) for autism spectrum disorder (ASD), this study aims to evaluate feasibility of study procedures, evaluate safety, document concomitant treatment, and report consistency of individuals' trends over time in chosen outcome measures. Children with ASD aged between 4 years, 0 months, and 6 years, 11 months, were randomly assigned to one of three conditions: one (low intensity) vs. three weekly IMT sessions (high intensity) for five months vs. standard care. Feasibility was evaluated by examining recruitment, implementation of study conditions, assessment procedures, blinding, and retention; we also evaluated safety, concomitant treatment, and consistency of changes in standardized scales completed by blinded assessors and parents before and 5 months after randomization. Within this subsample (n = 15), recruitment rates, session attendance in the high-intensity condition, and consistency between outcome measures were lower than expected. Session attendance in the low-intensity and control conditions, treatment fidelity, measurement completion, blinding, retention, and safety met a priori thresholds for feasibility. By discussing strategies to improve recruitment and to minimize potential burden on study participants, referrers, and researchers, this study helps build knowledge about designing and implementing trials successfully. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Outcomes after 18 months of eliglustat therapy in treatment‐naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial

PubMed Central

Lukina, Elena; Ben Turkia, Hadhami; Shankar, Suma P.; Baris, Hagit; Ghosn, Marwan; Mehta, Atul; Packman, Seymour; Pastores, Gregory; Petakov, Milan; Assouline, Sarit; Balwani, Manisha; Danda, Sumita; Hadjiev, Evgueniy; Ortega, Andres; Gaemers, Sebastiaan J. M.; Tayag, Regina; Peterschmitt, M. Judith

2017-01-01

Abstract Eliglustat, an oral substrate reduction therapy, is a first‐line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18‐month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double‐blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double‐blind period, eliglustat treatment during the 9‐month, open‐label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double‐blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment‐naïve patients. Eliglustat was well‐tolerated, and there were no new safety concerns with longer‐term exposure. PMID:28762527

A randomized controlled trial of comprehensive early intervention care in patients with first-episode psychosis in Japan: 1.5-year outcomes from the J-CAP study.

PubMed

Nishida, Atsushi; Ando, Shuntaro; Yamasaki, Syudo; Koike, Shinsuke; Ichihashi, Kayo; Miyakoshi, Yuji; Maekawa, Sanae; Nakamura, Tomohisa; Natsubori, Tatsunobu; Ichikawa, Eriko; Ishigami, Hiroki; Sato, Kojiro; Matsunaga, Asami; Smith, Jo; French, Paul; Harima, Hirohiko; Kishi, Yoshiki; Fujita, Izumi; Kasai, Kiyoto; Okazaki, Yuji

2018-04-08

The first episode of psychosis represents a critical period wherein comprehensive early intervention in psychosis (EIP) may alter the course of illness. However, evidence from randomized controlled trials that have examined the impact of comprehensive EIP care on clinical and functional recovery assessed by independent blinded raters is limited. The objective of this study was to conduct a single-blinded multicenter trial comparing comprehensive EIP care and standard care in young patients with first-episode psychosis (FEP) in Japan (J-CAP Study). A total of 77 participants with FEP (aged 15-35 years) were randomized to receive standard care or specialized comprehensive EIP care and were followed up for 1.5 years (trial no.: UMIN000005092). Function (measured with the Global Assessment of Functioning) and clinical remission (defined by internationally standardized criteria proposed by the Remission in Schizophrenia Working Group) were evaluated by independent raters who were blinded to group assignment. Dropout rate and other secondary outcomes were also examined. The specialized EIP care group had a higher clinical remission rate (odds ratio, 6.3; 95% confidence interval, 1.0-37.9) and lower treatment dropout rate (odds ratio, 0.038; 95% confidence interval, 0.002-0.923) than the standard care group, even after adjusting for baseline characteristics. Functional improvement in the specialized EIP care group was slightly higher than that in the standard care group, but this difference was not statistically significant (p = 0.195). From the results, we conclude that comprehensive EIP care may provide advantages over standard care in patients with FEP. Copyright © 2018. Published by Elsevier Ltd.

Tranexamic Acid versus Placebo to Prevent Blood Transfusion during Radical Cystectomy for Bladder Cancer (TACT): Study Protocol for a Randomized Controlled Trial.

PubMed

Breau, Rodney H; Lavallée, Luke T; Cnossen, Sonya; Witiuk, Kelsey; Cagiannos, Ilias; Momoli, Franco; Bryson, Gregory; Kanji, Salmaan; Morash, Christopher; Turgeon, Alexis; Zarychanski, Ryan; Mallick, Ranjeeta; Knoll, Greg; Fergusson, Dean A

2018-05-02

Radical cystectomy for bladder cancer is associated with a high risk of needing red blood cell transfusion. Tranexamic acid reduces blood loss during cardiac and orthopedic surgery, but no study has yet evaluated tranexamic acid use during cystectomy. A randomized, double-blind (surgeon-, anesthesiologist-, patient-, data-monitor-blinded), placebo-controlled trial of tranexamic acid during cystectomy was initiated in June 2013. Prior to incision, the intervention arm participants receive a 10 mg/kg loading dose of intravenously administered tranexamic acid, followed by a 5 mg/kg/h maintenance infusion. In the control arm, the patient receives an identical volume of normal saline that is indistinguishable from the intervention. The primary outcome is any blood transfusion from the start of surgery up to 30 days post operative. There are no strict criteria to mandate the transfusion of blood products. The decision to transfuse is entirely at the discretion of the treating physicians who are blinded to patient allocation. Physicians are allowed to utilize all resources to make transfusion decisions, including serum hemoglobin concentration and vital signs. To date, 147 patients of a planned 354 have been randomized to the study. This protocol reviews pertinent data relating to blood transfusion during radical cystectomy, highlighting the need to identify methods for reducing blood loss and preventing transfusion in patients receiving radical cystectomy. It explains the clinical rationale for using tranexamic acid to reduce blood loss during cystectomy, and outlines the study methods of our ongoing randomized controlled trial. Canadian Institute for Health Research (CIHR) Protocol: MOP-342559; ClinicalTrials.gov, ID: NCT01869413. Registered on 5 June 2013.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.

PubMed

Holtzheimer, Paul E; Husain, Mustafa M; Lisanby, Sarah H; Taylor, Stephan F; Whitworth, Louis A; McClintock, Shawn; Slavin, Konstantin V; Berman, Joshua; McKhann, Guy M; Patil, Parag G; Rittberg, Barry R; Abosch, Aviva; Pandurangi, Ananda K; Holloway, Kathryn L; Lam, Raymond W; Honey, Christopher R; Neimat, Joseph S; Henderson, Jaimie M; DeBattista, Charles; Rothschild, Anthony J; Pilitsis, Julie G; Espinoza, Randall T; Petrides, Georgios; Mogilner, Alon Y; Matthews, Keith; Peichel, DeLea; Gross, Robert E; Hamani, Clement; Lozano, Andres M; Mayberg, Helen S

2017-11-01

Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Abbott (previously St Jude Medical). Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension.

PubMed

Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

2015-08-07

Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K(+)-depletion. We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25-50 mg, amiloride 10-20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18-79, systolic BP on permitted background treatment ≥ 140 mm Hg and home BP ≥ 130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K(+), clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. 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.

Fixed, low radiant exposure vs. incremental radiant exposure approach for diode laser hair reduction: a randomized, split axilla, comparative single-blinded trial.

PubMed

Pavlović, M D; Adamič, M; Nenadić, D

2015-12-01

Diode lasers are the most commonly used treatment modalities for unwanted hair reduction. Only a few controlled clinical trials but not a single randomized controlled trial (RCT) compared the impact of various laser parameters, especially radiant exposure, onto efficacy, tolerability and safety of laser hair reduction. To compare the safety, tolerability and mid-term efficacy of fixed, low and incremental radiant exposures of diode lasers (800 nm) for axillary hair removal, we conducted an intrapatient, left-to-right, patient- and assessor-blinded and controlled trial. Diode laser (800 nm) treatments were evaluated in 39 study participants (skin type II-III) with unwanted axillary hairs. Randomization and allocation to split axilla treatments were carried out by a web-based randomization tool. Six treatments were performed at 4- to 6-week intervals with study subjects blinded to the type of treatment. Final assessment of hair reduction was conducted 6 months after the last treatment by means of blinded 4-point clinical scale using photographs. The primary endpoint was reduction in hair growth, and secondary endpoints were patient-rated tolerability and satisfaction with the treatment, treatment-related pain and adverse effects. Excellent reduction in axillary hairs (≥ 76%) at 6-month follow-up visit after receiving fixed, low and incremental radiant exposure diode laser treatments was obtained in 59% and 67% of study participants respectively (Z value: 1.342, P = 0.180). Patients reported lower visual analogue scale (VAS) pain score on the fixed (4.26) than on the incremental radiant exposure side (5.64) (P < 0.0003). The only side-effect was mild and transient erythema. Subjects better tolerated the fixed, low radiant exposure protocol (P = 0.03). The majority of the study participants were satisfied with both treatments. Both low and incremental radiant exposures produced similar hair reduction and high and comparable patient satisfaction. However, low radiant exposure diode laser treatments were less painful and better tolerated. © 2015 European Academy of Dermatology and Venereology.

Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Williams, Kyle A; Swedo, Susan E; Farmer, Cristan A; Grantz, Heidi; Grant, Paul J; D'Souza, Precilla; Hommer, Rebecca; Katsovich, Liliya; King, Robert A; Leckman, James F

2016-10-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross-reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS. A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. "Responders" were defined, a priori, by a ≥ 30% decrease in CY-BOCS total score, and a "much" or "very much" improved rating on CGI-I. During the double-blind phase, the mean decrease in CY-BOCS score was 24% ± 31% in the IVIG group (n = 17) and 12% ± 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double-blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% ± 33% at week 12 and 62% ± 33% at week 24. IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information-Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666. Published by Elsevier Inc.

Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Leitner, Lorenz; Sybesma, Wilbert; Chanishvili, Nina; Goderdzishvili, Marina; Chkhotua, Archil; Ujmajuridze, Aleksandre; Schneider, Marc P; Sartori, Andrea; Mehnert, Ulrich; Bachmann, Lucas M; Kessler, Thomas M

2017-09-26

Urinary tract infections (UTI) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming. Thus, well-tolerated, highly effective therapeutic alternatives are urgently needed. Although there is evidence indicating that bacteriophage therapy may be effective and safe for treating UTIs, the number of investigated patients is low and there is a lack of randomized controlled trials. This study is the first randomized, placebo-controlled, double-blind trial investigating bacteriophages in UTI treatment. Patients planned for transurethral resection of the prostate are screened for UTIs and enrolled if in urine culture eligible microorganisms ≥10 4 colony forming units/mL are found. Patients are randomized in a double-blind fashion to the 3 study treatment arms in a 1:1:1 ratio to receive either: a) bacteriophage (i.e. commercially available Pyo bacteriophage) solution, b) placebo solution, or c) antibiotic treatment according to the antibiotic sensitivity pattern. All treatments are intended for 7 days. No antibiotic prophylaxes will be given to the double-blinded treatment arms a) and b). As common practice, the Pyo bacteriophage cocktail is subjected to periodic adaptation cycles during the study. Urinalysis, urine culture, bladder and pain diary, and IPSS questionnaire will be completed prior to and at the end of treatment (i.e. after 7 days) or at withdrawal/drop out from the study. Patients with persistent UTIs will undergo antibiotic treatment according to antibiotic sensitivity pattern. Based on the high lytic activity and the potential of resistance optimization by direct adaptation of bacteriophages, and considering the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a very promising treatment option for UTIs. Thus, our randomized controlled trial investigating bacteriophages for treating UTIs will provide essential insights into this potentially revolutionizing treatment option. This study has been registered at clinicaltrials.gov ( www.clinicaltrials.gov/ct2/show/NCT03140085 ). April 27, 2017.

Ratings of perceived exertion in braille: validity and reliability in production mode.

PubMed

Buckley, J P; Eston, R G; Sim, J

2000-08-01

(a) To assess the validity and reliability of producing and reproducing a given exercise intensity during cycle ergometry using a braille version of Borg's standard 6-20 rating of perceived exertion (RPE) scale, and (b) to determine whether the exercise responses of blind participants, at a given produced RPE, were similar to those reported in recognised guidelines for sighted subjects. Ten healthy registered blind volunteer participants (four women, six men; mean (SD) age 23.2 (9.0) years) performed an initial graded exercise cycle test to determine maximal heart rate (HRMAx) and maximal oxygen uptake (VO2MAX). Three trials of three exercise bouts at RPEs 9, 11, and 13 were then performed in random order on three separate days of the same week, with expired air and heart rate measured continuously. Each exercise bout was followed by 10 minutes of rest. The validity of the scale as a means of producing different exercise intensities was assessed using a two factor (RPE x trial) repeated measures analysis of variance. Intertrial reliability was assessed using intraclass correlation coefficients (ICC) and the bias +/-95% limits of agreement (95%LoA) procedure. Participants reported no difficulty in using the braille RPE scale. When asked to produce exercise intensities equating to RPE 9, 11, and 13, they elicited mean %VO2MAX values of 47%, 53%, and 63% respectively. Analysis of variance showed no significant differences in either %HRMAx or %VO2MAX between trials at each of the three RPEs, but there was a significant difference (p<0.001) in both %HRMAx and %VO2MAX between the three RPE levels. All pairwise comparisons of the three different RPEs were significantly different (p<0.016). The ICC between the second and third trial for %HRMAx was significant (p <0.05) for all three RPEs. Similarly for %VO2MAX, the ICC was significant for RPE 9 and 11 but not 13. The 95%LoA decreased for both %HRMAx and %VO2MAX with each successive trial. Blind participants were successful in using a braille RPE scale to differentiate exercise intensity on a cycle ergometer. In every trial at RPE 13, all participants achieved %HRMAX and %VO2MAX levels, which fell within the recommendedrange for developing cardiorespiratory fitness. Using %HRMAx as a judge of intertrial reliability, the participants were able to repeat similar exercise intensities after two trials at each of the three RPEs (9, 11,13). The same was true for RPE 9 and 11, when %VO2MAX was used as a judge, but further trials were required to achieve similar reliability at RPE 13. A braille RPE scale can be used by healthy blind people during cycle ergometry, with similar effect to the visual analogue scale recommended for use in healthy sighted people.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. 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/.

Cervical dystonia: effectiveness of a standardized physical therapy program; study design and protocol of a single blind randomized controlled trial

PubMed Central

2013-01-01

Background Cervical dystonia is characterized by involuntary muscle contractions of the neck and abnormal head positions that affect daily life activities and social life of patients. Patients are usually treated with botulinum toxin injections into affected neck muscles to relief pain and improve control of head postures. In addition, many patients are referred for physical therapy to improve their ability to perform activities of daily living. A recent review on allied health interventions in cervical dystonia showed a lack of randomized controlled intervention studies regarding the effectiveness of physical therapy interventions. Methods/design The (cost-) effectiveness of a standardized physical therapy program compared to regular physical therapy, both as add-on treatment to botulinum toxin injections will be determined in a multi-centre, single blinded randomized controlled trial with 100 cervical dystonia patients. Primary outcomes are disability in daily functioning assessed with the disability subscale of the Toronto Western Spasmodic Torticollis Rating Scale. Secondary outcomes are pain, severity of dystonia, active range of motion of the head, quality of life, anxiety and depression. Data will be collected at baseline, after six months and one year by an independent blind assessor just prior to botulinum toxin injections. For the cost effectiveness, an additional economic evaluation will be performed with the costs per quality adjusted life-year as primary outcome parameter. Discussion Our study will provide new evidence regarding the (cost-) effectiveness of a standardized, tailored physical therapy program for patients with cervical dystonia. It is widely felt that allied health interventions, including physical therapy, may offer a valuable supplement to the current therapeutic options. A positive outcome will lead to a greater use of the standardized physical therapy program. For the Dutch situation a positive outcome implies that the standardized physical therapy program forms the basis for a national treatment guideline for cervical dystonia. Trial registration Number Dutch Trial registration (Nederlands Trial Register): NTR3437 PMID:23855591

Overview of registered studies in orthodontics: Evaluation of the ClinicalTrials.gov registry.

PubMed

Allareddy, Veerasathpurush; Rampa, Sankeerth; Masoud, Mohamed I; Lee, Min Kyeong; Nalliah, Romesh; Allareddy, Veerajalandhar

2014-11-01

The Food and Drug Administration Modernization Act of 1997 made it mandatory for all phase II through IV trials regulated by this Act to be registered. After this, the National Institutes of Health created ClinicalTrials.gov, which is a registry of publicly and privately supported clinical studies of human participants. The objective of this study was to examine the characteristics of registered studies in orthodontics. The ClinicalTrials.gov Web site was used to query all registered orthodontic studies. The search term used was "orthodontics." No limitations were placed for the time period. All registered studies regardless of their recruitment status, study results, and study type were selected for analysis. A total of 64 orthodontic studies were registered as of January 1, 2014. Of these, 52 were interventional, and 12 were observational. Close to 60% of the interventional studies and 66.7% of the observational studies had sample sizes of 50 or fewer subjects. About 21.2% of the interventional studies and 16.7% of the observational studies had sample sizes greater than 100. Only 1 study was funded by the National Institutes of Health, and the rest were funded by "other" or "industry" sources. Close to 87.7% of the interventional studies were randomized. Interventional model assignments included factorial assignment (3.9%), parallel assignments (74.5%), crossover assignment (7.8%), and single-group assignment (13.7%). Most studies were treatment oriented (80.4%). The types of masking used by the interventional studies included open label (28.9%), single blind (44.2%), and double blind (26.9%). Outcome assessors were blinded in only 6 studies. Orthodontic studies registered in ClinicalTrials.gov are dominated by small single-center studies. There are wide variations with regard to treatment allocation approaches and randomization methods in the studies. These results also indicate the need for multicenter clinical studies in orthodontics. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

PubMed

Mathiassen, Ole N; Vase, Henrik; Bech, Jesper N; Christensen, Kent L; Buus, Niels H; Schroeder, Anne P; Lederballe, Ole; Rickers, Hans; Kampmann, Ulla; Poulsen, Per L; Hansen, Klavs W; Btker, Hans E; Peters, Christian D; Engholm, Morten; Bertelsen, Jannik B; Lassen, Jens F; Langfeldt, Sten; Andersen, Gratien; Pedersen, Erling B; Kaltoft, Anne

2016-08-01

Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Effectiveness of transcranial direct current stimulation preceding cognitive behavioural management for chronic low back pain: sham controlled double blinded randomised controlled trial.

PubMed

Luedtke, Kerstin; Rushton, Alison; Wright, Christine; Jürgens, Tim; Polzer, Astrid; Mueller, Gerd; May, Arne

2015-04-16

To evaluate the effectiveness of transcranial direct current stimulation alone and in combination with cognitive behavioural management in patients with non-specific chronic low back pain. Double blind parallel group randomised controlled trial with six months' follow-up conducted May 2011-March 2013. Participants, physiotherapists, assessors, and analyses were blinded to group allocation. Interdisciplinary chronic pain centre. 135 participants with non-specific chronic low back pain >12 weeks were recruited from 225 patients assessed for eligibility. Participants were randomised to receive anodal (20 minutes to motor cortex at 2 mA) or sham transcranial direct current stimulation (identical electrode position, stimulator switched off after 30 seconds) for five consecutive days immediately before cognitive behavioural management (four week multidisciplinary programme of 80 hours). Two primary outcome measures of pain intensity (0-100 visual analogue scale) and disability (Oswestry disability index) were evaluated at two primary endpoints after stimulation and after cognitive behavioural management. Analyses of covariance with baseline values (pain or disability) as covariates showed that transcranial direct current stimulation was ineffective for the reduction of pain (difference between groups on visual analogue scale 1 mm (99% confidence interval -8.69 mm to 6.3 mm; P=0.68)) and disability (difference between groups 1 point (-1.73 to 1.98; P=0.86)) and did not influence the outcome of cognitive behavioural management (difference between group 3 mm (-10.32 mm to 6.73 mm); P=0.58; difference between groups on Oswestry disability index 0 point (-2.45 to 2.62); P=0.92). The stimulation was well tolerated with minimal transitory side effects. This results of this trial on the effectiveness of transcranial direct current stimulation for the reduction of pain and disability do not support its clinical use for managing non-specific chronic low back pain.Trial registration Current controlled trials ISRCTN89874874. © Luedtke et al 2015.

Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in mildly hypercholesterolemic adults: a double-blinded, randomized, placebo-controlled study

PubMed Central

2014-01-01

Background High level of serum cholesterol is considered to be a major risk factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo-controlled trial was performed to test the hypothesis that a daily intake of Chlorella may improve serum lipid profile through enhancement of serum carotenoid concentration in mildly hypercholesterolemic subjects. Methods Eligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial. Results Compared with the control group, the Chlorella group exhibited remarkable changes in total cholesterol (Chlorella −1.6%; placebo 0.03%; P = 0.036), triglycerides (Chlorella −10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%; placebo −1.7%; P < 0.0001), and α-carotene (Chlorella 163.6%; placebo 15%; P < 0.0001). Improvement of serum lipids was supported by significant reductions of very low-density lipoprotein cholesterol (Chlorella −11%; placebo 11.8%; P = 0.006), apolipoprotein B (Chlorella −1.5%; placebo 1.7%; P = 0.044), non high-density lipoprotein (Chlorella −2.6%; placebo −0.5%; P = 0.032), and high-density lipoprotein/triglycerides (Chlorella 4.0%; placebo −9.5%; P = 0.023), suggesting an inhibitory effect of Chlorella on the intestinal absorption of dietary and endogenous lipids. Further, the changes of serum lipids appeared to be associated with the changes of serum carotenoids. Conclusion Daily consumption of Chlorella supplements provided the potential of health benefits reducing serum lipid risk factors, mainly triglycerides and total cholesterol, in mildly hypercholesterolemic subjects. The effect was related to carotenoid consumption. Trial registration WHO International Clinical Trials Registry Platform KCT0000259. PMID:24920270

Exercise, education, manual-therapy and taping compared to education for patellofemoral osteoarthritis: a blinded, randomised clinical trial.

PubMed

Crossley, K M; Vicenzino, B; Lentzos, J; Schache, A G; Pandy, M G; Ozturk, H; Hinman, R S

2015-09-01

Patellofemoral joint osteoarthritis (PFJ OA) contributes considerably to knee OA symptoms. This study aimed to determine the efficacy of a PFJ-targeted exercise, education manual-therapy and taping program compared to OA education alone, in participants with PFJ OA. A randomised, participant-blinded and assessor-blinded clinical trial was conducted in primary-care physiotherapy. 92 people aged ≥40 years with symptomatic and radiographic PFJ OA participated. Physiotherapists delivered the PFJ-targeted exercise, education, manual-therapy and taping program, or the OA-education (control condition) in eight sessions over 12 weeks. Primary outcomes at 3-month (primary) and 9-month follow-up: (1) patient-perceived global rating of change (2) pain visual analogue scale (VAS) (100 mm); and (3) activities of daily living (ADL) subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS). 81 people (88%) completed the 3-month follow-up and data analysed on an intention-to-treat basis. Between-group baseline similarity for participant characteristics was observed. The exercise, education, manual-therapy and taping program resulted in more people reporting much improvement (20/44) than the OA-education group (5/48) (number needed to treat 3 (95% confidence interval (CI) 2 to 5)) and greater pain reduction (mean difference: -15.2 mm, 95% CI -27.0 to -3.4). No significant effects on ADL were observed (5.8; 95% CI -0.6 to 12.1). At 9 months there were no significant effects for self-report of improvement, pain (-10.5 mm, 95% CI -22.7 to 1.8) or ADL (3.0, 95% CI -3.7 to 9.7). Exercise, education, manual-therapy and taping can be recommended to improve short-term patient rating of change and pain severity. However over 9-months, both options were equivalent. Australian New Zealand Clinical Trials Registry (ACTRN12608000288325): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82878. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project.

PubMed

Merle, Corinne S C; Sismanidis, Charalambos; Sow, Oumou Bah; Gninafon, Martin; Horton, John; Lapujade, Olivier; Lo, Mame Bocar; Mitchinson, Denis A; Perronne, Christian; Portaels, Francoise; Odhiambo, Joseph; Olliaro, Piero; Rustomjee, Roxana; Lienhardt, Christian; Fielding, Katherine

2012-05-18

There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection.

A Quantitative Assessment of the Reporting Quality of Herbal Medicine Research: The Road to Improvement.

PubMed

Naumann, Ken

2018-02-01

To quantify different aspects of the quality of reporting of herbal medicine clinical trials, to determine how that quality is affecting the conclusions of meta-analyses, and to target areas for improvement in future herbal medicine research reporting. The Electronic databases PubMed, Academic Search Premier, ScienceDirect, and Alt HealthWatch were searched for meta-analyses of herbal medicines in refereed journals and Cochrane Reviews in the years 2000-2004 and 2010-2014. The search was limited to meta-analyses of randomized controlled trials involving humans and published in English. Judgments and descriptions within the meta-analyses were used to report on risks of bias in the included clinical trials and the meta-analyses themselves. Out of 3264 citations, 9 journal-published meta-analyses were selected from 2000 to 2004, 116 from 2010 to 2014, and 44 Cochrane Reviews from 2010 to 2014. Across both time frames and categories of publication, <42% of the trials included in the meta-analyses described adequate randomization; <19% described concealment methods; <26% described double blinding; <29% described outcome assessment blinding, ≤53% discussed incomplete data, and <36% were nonselective in their reporting. Less than 54% of trials reported on adverse events and 64% of meta-analyses did not include a single trial with a low risk of bias. Taxonomic verification and chemical characterization of test products were infrequent in trials. Only 40% of meta-analyses considered publication bias and, of those that did, 90% found evidence for it. Cochrane Reviews were more likely than other sources to make negative conclusions of efficacy or to defer conclusions because of the absence of high quality trials. Meta-analyses of herbal medicines include a significant number of clinical trials that do not meet the recommended standards for clinical trial reporting. This quantitative assessment identified significant publication bias and other bias risks that may be due to inadequate trial design or incomplete reporting of outcomes. Suggested improvements to herbal medicine clinical trial reporting are discussed.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project

PubMed Central

2012-01-01

Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish between relapse and re-infection. PMID:22607233

Transporting Clinical Research to Community Settings: Designing and Conducting a Multisite Trial of Brief Strategic Family Therapy

PubMed Central

Robbins, Michael S.; Alonso, Elizabeth; Horigian, Viviana E.; Bachrach, Ken; Burlew, Kathy; Carrión, Ibis S.; Hodgkins, Candace C.; Miller, Michael; Schindler, Eric; VanDeMark, Nancy; Henderson, Craig; Szapocznik, José

2010-01-01

This paper describes the development and implementation of a trial of Brief Strategic Family Therapy (BSFT), an evidence-based drug intervention for adolescents, in eight community substance abuse treatment programs. Researchers and treatment programs collaborated closely to identify and overcome challenges, many of them related to achieving results that were both scientifically rigorous and applicable to the widest possible variety of adolescent substance abuse treatment programs. To meet these challenges, the collaborative team drew on lessons and practices from efficacy, effectiveness, and implementation research. PMID:22002455

[Problems of study designs with randomization, blinding and placebos].

PubMed

Heusser, P

1999-04-01

As randomised double-blind trials are not rarely demanded as a prerequisite for the scientific acceptance of complementary medicine, the author has analysed the soundness of this demand on the basis of the international literature. As a result there appeared a number of methodological, practical and ethical problems which question the theoretically deduced primal value of this study design relative to the needs of medical practice and of health insurance issues. The experimental instruments of randomisation, blinding and placebo deliberately exclude essential therapeutic factors which are integral elements of complementary medical concepts; therefore, it is suggested to supplement quantitatively and collectively oriented experimental research by non-experimental procedures, which adequately reflect the context- and practice-related individual reality.

Customizing chemotherapy in non-small cell lung cancer: the promise is still unmet

PubMed Central

2015-01-01

A combination of cytotoxic agents with cis-platin remains the cornerstone of treatment for the vast majority of patients with non-small cell lung cancer (NSCLC). Molecular analysis of the primary may lead better prognostication and eventually in more accurate therapeutic approaches. Data from retrospective analysis of randomized trials as well as large patients’ series have suggested that chemotherapy may be customized upon molecular-genetic analysis of the tumor cells. The Spanish Lung Cancer Group (SLCG) in collaboration with French lung Cancer Group (FLCG) had conduct randomized, phase III, biomarkers-driven trial and supported simultaneously a randomized phase II trial in collaborating centers in China. Despite the evidence from the preclinical data and the results from the retrospective studies, the results of these trials published recently in Annals of Oncology were in favor of ‘standard approach’. The present commentary tries to give some explanation for the disappointing results, provide potential solution for the future trials and explain why the vision of customizing treatment is still alive. PMID:26629440

Competencies for Teachers of Learners Who Are Deafblind: Perkins National Deafblind Training Project.

ERIC Educational Resources Information Center

McLetchie, Barbara A. B.; Riggio, Marianne

The statements of knowledge and skills contained in this manual are the outcome of a collaborative process involving a committee that included the project staff, university level faculty, and a state coordinator of deaf-blind services. The competencies are designed for use as a blueprint for course development and field experiences by university…

Observed Gender Differences in African American Mother-Child Relationships and Child Behavior

ERIC Educational Resources Information Center

Mandara, Jelani; Murray, Carolyn B.; Telesford, James M.; Varner, Fatima A.; Richman, Scott B.

2012-01-01

African American mother-child dyads (N = 99) were observed interacting on a collaborative puzzle exercise. Raters blind to the purpose of the study rated the dyads on several mother and child behaviors. Mothers of daughters were rated as more empathetic, encouraging, warm, and accepting and less negative than mothers of sons. Male children were…

Locally Learning Biomedical Data Using Diffusion Frames

DTIC Science & Technology

2012-01-01

age - related macular degeneration (AMD) patients. All eye- related data were collected by our collaborators at the...in Table 2. 6.2. Age - related macular degeneration Age - related macular degeneration is the most common cause of blindness among the elderly population...maculopathy and age - related macular degeneration . The international ARM epidemiological study group. Surv. Ophthalmol. 39, 367–374.

Cost-Effectiveness of Collaborative Care for Depression in UK Primary Care: Economic Evaluation of a Randomised Controlled Trial (CADET)

PubMed Central

Green, Colin; Richards, David A.; Hill, Jacqueline J.; Gask, Linda; Lovell, Karina; Chew-Graham, Carolyn; Bower, Peter; Cape, John; Pilling, Stephen; Araya, Ricardo; Kessler, David; Bland, J. Martin; Gilbody, Simon; Lewis, Glyn; Manning, Chris; Hughes-Morley, Adwoa; Barkham, Michael

2014-01-01

Background Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking. Aims To assess the cost-effectiveness of collaborative care in a UK primary care setting. Methods An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane. Results The collaborative care intervention had a mean cost of £272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: –0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of £270.72 (95% CI: –202.98, 886.04), and resulted in an estimated mean cost per QALY of £14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual. Conclusion Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting. PMID:25121991

Glomerular disease: why is there a dearth of high quality clinical trials?

PubMed

Leaf, David E; Appel, Gerald B; Radhakrishnan, Jai

2010-08-01

There is a paucity of high quality clinical trials in glomerular disease, particularly in non-diabetic kidney disease. The aims of this review include quantifying the extent of this problem and exploring reasons for the scarcity of such trials in primary glomerular disease, with an emphasis on immunoglobulin A nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy in comparison with the more common diseases of diabetic nephropathy and lupus nephritis. Reasons for the dearth of high quality clinical trials in primary glomerular disease include (1) low prevalence of disease; (2) variability in clinical presentation; (3) variability in treatment response; (4) lack of consensus in definitions; (5) difficulty in recruiting patients; (6) high costs of randomized controlled trials; and (7) lack of collaborative efforts. To facilitate greater numbers of high quality clinical trials in glomerular disease, practice guidelines should establish common classification systems of disease and common clinical end points, industry and non-industry sponsored research should find common ground and work together toward advancing science, and national registries should be created to encourage collaborations across institutions and across nations.

An investigator-blinded, randomized study to compare the efficacy of combined CBT for alcohol use disorders and social anxiety disorder versus CBT focused on alcohol alone in adults with comorbid disorders: the Combined Alcohol Social Phobia (CASP) trial protocol

PubMed Central

2013-01-01

Background Alcohol use disorders and social anxiety disorder are common and disabling conditions that frequently co-exist. Although there are efficacious treatments for each disorder, only two randomized controlled trials of interventions for these combined problems have been published. We developed a new integrated treatment for comorbid Social Anxiety Disorder and Alcohol Use Disorder based on established Motivational Interviewing (MI) and Cognitive Behaviour Therapy (CBT) interventions for the separate disorders. Compared to established MI/CBT for alcohol use disorders this new intervention is hypothesised to lead to greater reductions in symptoms of social anxiety and alcohol use disorder and to produce greater improvements in quality of life. Higher levels of alcohol dependence will result in relatively poorer outcomes for the new integrated treatment. Methods/design A randomised controlled trial comparing 9 sessions of individual integrated treatment for alcohol and social phobia with 9 sessions of treatment for alcohol use problems alone is proposed. Randomisation will be stratified for stable antidepressant use. Post treatment clinical assessments of alcohol consumption and diagnostic status at 3 and 6 month follow-up will be blind to allocation. Discussion The proposed trial addresses a serious gap in treatment evidence and could potentially define the appropriate treatment for a large proportion of adults affected by these problems. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12608000228381. PMID:23895258

Potential for specific dihydropyridine calcium channel blockers to have a positive impact on cognitive function in humans: a systematic review

PubMed Central

Peters, Jean; Booth, Andrew

2015-01-01

Background: There is some evidence to suggest a possible association between calcium channel blocker (CCB) use and a lower decline in cognitive function compared with use of other hypertensive treatments. In particular, there is an emerging interest in the potential for specific CCBs, particularly the dihydropyridine CCBs nitrendipine, nicardipine, cilnidipine, lercandipine, nimodipine, azelnidipine and nilvadipine. The aim of this review was to assess the evidence relating to these specific CCBs and incident cognitive decline or dementia in humans. Methods: A systematic review of the literature was carried out. The databases MEDLINE, Embase and PsychINFO were searched from 1980 to 18 April 2014. All abstracts were reviewed by two independent reviewers. Results: From 753 unique records, 16 full text articles were examined and three retained. The three articles reported data from two studies. A 12-week double-blind randomized controlled trial of nitrendipine compared with cilazapril and a longer and larger double-blind placebo-controlled trial also of nitrendipine, namely the Systolic Hypertension in Europe trial (SYST-EUR). Nitrendipine was associated with a reduction in incident dementia in the SYST-EUR trial. There was no association seen for cognitive outcomes in the smaller trial. Conclusion: At present there is limited evidence to suggest that nitrendipine may be associated with reduction in incident dementia. This association comes from a single trial and needs to be replicated. Furthermore, there is no high-quality evidence for any of the other potential candidate CCBs. PMID:26137206

Clinical trial quality: From supervision to collaboration and beyond.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen

2018-02-01

Over the past decade, clinical trial quality has evolved from an after-the-fact, reactive activity to one focused on the important work of evidence generation from well-designed trials. This article explores the role the Clinical Trials Transformation Initiative has played in advancing quality as a core element of clinical trial design, through project work that initially focused on monitoring but evolved into a holistic, prospective, and comprehensive quality by design approach to clinical trial design and conduct.

Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

USDA-ARS?s Scientific Manuscript database

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

A Comparison of Teacher Checklists Used over 15 Days and a One-Day Antecedent Analysis to Conduct a Medication Trial

ERIC Educational Resources Information Center

Smith, R.; Larsen, D.; Derby, K. M.; McLaughlin, T. F.; Weber, K. P.; Brown, K.; Herring, M.

2004-01-01

A one-day antecedent analysis and an extended school-based double-blind medication trial were used to assess the effects of Ritalin on the disruptive behavior of a child diagnosed with ADHD. The evaluations took place in an outpatient clinic and in the child's general education classroom. The results of both evaluations indicated that the…

The PEDALS Stationary Cycling Intervention and Health-Related Quality of Life in Children with Cerebral Palsy: A Randomized Controlled Trial

ERIC Educational Resources Information Center

DeMuth, Sharon K.; Knutson, Loretta M.; Fowler, Eileen G.

2012-01-01

Aim: The aim of this study was to assess health-related quality of life (HRQOL) following a stationary cycling intervention in children with cerebral palsy (CP). Method: This was a phase I multisite randomized controlled trial with single blinding. HRQOL was evaluated using the Pediatric Quality of Life Inventory SF15 (PedsQL; children) and…

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

PubMed

Naseri, Mohammad Hassan; Madani, Hoda; Ahmadi Tafti, Seyed Hossein; Moshkani Farahani, Maryam; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Hossein Ahmadi, Zargham; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharafi, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Fattah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdol Hosein; Baharvand, Hossein; Aghdami, Nasser

2018-10-01

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request. Copyright© by Royan Institute. All rights reserved.

Effects of a Web-Based Decision Aid Regarding Diagnostic Self-Testing. A Single-Blind Randomized Controlled Trial

ERIC Educational Resources Information Center

Ickenroth, Martine H. P.; Grispen, J. E. J.; de Vries, N. K.; Dinant, G. J.; Ronda, G.; van der Weijden, T.

2016-01-01

Currently, there are many diagnostic self-tests on body materials available to consumers. The aim of this study was to assess the effect of an online decision aid on diagnostic self-testing for cholesterol and diabetes on knowledge among consumers with an intention to take these tests. A randomized controlled trial was designed. A total of 1259…

Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Trial

ERIC Educational Resources Information Center

Sallee, Floyd R.; McGough, James; Wigal, Tim; Donahue, Jessica; Lyne, Andrew; Biederman, Joseph

2009-01-01

A double-blind, 9-week, randomized trial was done to compare the efficacy of guanfacine extended release (GXR) with a placebo in treating children and adolescents with attention-deficit/hyperactivity disorders (ADHD). Results find a significant reduction in ADHD from baseline to endpoint for all daily doses of GXR which were measured at 1-, 2-,…

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.

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial.

PubMed

Han, Gajin; Park, Jae-Woo; Ko, Seok-Jae; Son, Jihee; Seon, Jongki; Kim, Juyeon; Kim, Seulki; Yeo, Inkwon; Ryu, Bongha; Kim, Jinsung

2013-09-03

Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients' quality of life. In traditional Korean medicine, 'Yin-Deficiency' has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve 'Yin-Deficiency', and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that 'Yin-Deficiency' is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and 'Yin-Deficiency'. This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by demonstrating its therapeutic effects in a well-designed clinical trial. ClinicalTrials.gov Identifier: NCT01579877.

Cancer Clinical Trials at the National Institutes of Health Clinical Center

MedlinePlus

... Data Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... fosters interaction and collaboration among clinicians and researchers. Medical Care at the Clinical Center Is Free Another ...