A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Insurance in clinical research

PubMed Central

Ghooi, Ravindra B.; Divekar, Deepa

2014-01-01

Aims and Objectives: Sponsors need to pay for management of all serious adverse events suffered by subjects in a clinical trial and to compensate for injuries or deaths related to the trial. This study examines if insurance policies of trials, cover all contingencies that require reimbursement or compensation. Materials and Methods: Insurance policies of trials submitted to Sahyadri Hospitals between January 2013 and December 2013 were studied, with respect to the policy period, the limit of liability, deductibles, and preconditions if any. Results: All the policies studied had some deficiencies, in one respect or the other and none had a provision to pay full compensation if required. Some insurers have put in preconditions that could jeopardize the payment of compensation to subjects. Conclusions: Insurances are complicated documents, and need to be critically examined by the ethics committee before approval of the study documents. PMID:25276622

Interventions for increasing fruit and vegetable consumption in children aged five years and under.

PubMed

Hodder, Rebecca K; Stacey, Fiona G; O'Brien, Kate M; Wyse, Rebecca J; Clinton-McHarg, Tara; Tzelepis, Flora; James, Erica L; Bartlem, Kate M; Nathan, Nicole K; Sutherland, Rachel; Robson, Emma; Yoong, Sze Lin; Wolfenden, Luke

2018-01-25

Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases, including cardiovascular disease. To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and Embase to identify eligible trials on 25 September 2017. We searched Proquest Dissertations and Theses and two clinical trial registers in November 2017. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included studies to identify further potentially relevant trials. We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. Two review authors independently extracted data and assessed the risks of bias of included studies; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures. We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. We included 55 trials with 154 trial arms and 11,108 participants. Thirty-three trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Thirteen trials examined the impact of parent nutrition education in increasing child fruit and vegetable intake. Eight studies examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. One study examined the effect of a nutrition intervention delivered to children in increasing child fruit and vegetable intake.We judged 14 of the 55 included trials as free from high risks of bias across all domains; performance, detection and attrition bias were the most common domains judged at high risk of bias for the remaining studies.Meta-analysis of trials examining child-feeding practices versus no intervention revealed a positive effect on child vegetable consumption (SMD 0.38, 95% confidence interval (CI) 0.15 to 0.61; n = 1509; 11 studies; very low-quality evidence), equivalent to a mean difference of 4.03 g of vegetables. There were no short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.11, 95% CI -0.05 to 0.28; n = 3023; 10 studies; very low-quality evidence) or multicomponent interventions versus no intervention (SMD 0.28, 95% CI -0.06 to 0.63; n = 1861; 4 studies; very low-quality evidence).Insufficient data were available to assess long-term effectiveness, cost effectiveness and unintended adverse consequences of interventions. Studies reported receiving governmental or charitable funds, except for three studies reporting industry funding. Despite identifying 55 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains sparse. There was very low-quality evidence that child-feeding practice interventions are effective in increasing vegetable consumption in children aged five years and younger, however the effect size was very small and long-term follow-up is required. There was very low-quality evidence that parent nutrition education and multicomponent interventions are not effective in increasing fruit and vegetable consumption in children aged five years and younger. All findings should be considered with caution, given most included trials could not be combined in meta-analyses. Given the very low-quality evidence, future research will very likely change estimates and conclusions. Such research should adopt more rigorous methods to advance the field.This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Rationale and design of the vitamin D and type 2 diabetes (D2d) study: a diabetes prevention trial

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supp...

Randomized controlled trials in mild cognitive impairment

PubMed Central

Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

2017-01-01

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale–cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating–sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings. PMID:28381516

There's a Bug in Your Ear!: Using Technology to Increase the Accuracy of DTT Implementation

ERIC Educational Resources Information Center

McKinney, Tracy; Vasquez, Eleazar, III.

2014-01-01

Many professionals have successfully implemented discrete trial teaching in the past. However, there have not been extensive studies examining the accuracy of discrete trial teaching implementation. This study investigated the use of Bug in Ear feedback on the accuracy of discrete trial teaching implementation among two pre-service teachers…

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

From Planning to Implementation: An Examination of Changes in the Research Design, Sample Size, and Precision of Group Randomized Trials Launched by the Institute of Education Sciences

ERIC Educational Resources Information Center

Spybrook, Jessaca; Puente, Anne Cullen; Lininger, Monica

2013-01-01

This article examines changes in the research design, sample size, and precision between the planning phase and implementation phase of group randomized trials (GRTs) funded by the Institute of Education Sciences. Thirty-eight GRTs funded between 2002 and 2006 were examined. Three studies revealed changes in the experimental design. Ten studies…

STEPS: A NARRATIVE ACCOUNT OF A GABAPENTIN SEEDING TRIAL

PubMed Central

Krumholz, Samuel D.; Egilman, David S.; Ross, Joseph S.

2012-01-01

Background Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. Methods We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing v. Pfizer and Franklin v. Warner-Lambert, the majority of which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial, in order to identify key themes related to the trial’s conduct and determine the extent of marketing involvement in its planning and implementation. Results Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company’s marketing plans. Documents demonstrated that several external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in two published papers. Conclusions The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation. PMID:21709111

The STRIDE (Strategies to Increase confidence, InDependence and Energy) study: cognitive behavioural therapy-based intervention to reduce fear of falling in older fallers living in the community - study protocol for a randomised controlled trial.

PubMed

Parry, Steve W; Deary, Vincent; Finch, Tracy; Bamford, Claire; Sabin, Neil; McMeekin, Peter; O'Brien, John; Caldwell, Alma; Steen, Nick; Whitney, Susan L; Macdonald, Claire; McColl, Elaine

2014-06-06

Around 30% to 62% of older individuals fall each year, with adverse consequences of falls being by no means limited to physical injury and escalating levels of dependence. Many older individuals suffer from a variety of adverse psychosocial difficulties related to falling including fear, anxiety, loss of confidence and subsequent increasing activity avoidance, social isolation and frailty. Such 'fear of falling' is common and disabling, but definitive studies examining the effective management of the syndrome are lacking. Cognitive behavioural therapy has been trialed with some success in a group setting, but there is no adequately powered randomised controlled study of an individually based cognitive behavioural therapy intervention, and none using non-mental health professionals to deliver the intervention. We are conducting a two-phase study examining the role of individual cognitive behavioural therapy delivered by healthcare assistants in improving fear of falling in older adults. In Phase I, the intervention was developed and taught to healthcare assistants, while Phase II is the pragmatic randomised controlled study examining the efficacy of the intervention in improving fear of falling in community-dwelling elders attending falls services. A qualitative process evaluation study informed by Normalization Process Theory is being conducted throughout to examine the potential promoters and inhibitors of introducing such an intervention into routine clinical practice, while a health economic sub-study running alongside the trial is examining the costs and benefits of such an approach to the wider health economy. Current Controlled Trials ISRCTN78396615.

Incorporating Multiple Secondary Targets into Learning Trials for Individuals with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Nottingham, Casey L.; Vladescu, Jason C.; Kodak, Tiffany; Kisamore, April N.

2017-01-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary…

The Effects of Interactive and Passive Distraction on Cold Pressor Pain in Preschool-aged Children

PubMed Central

Dahlquist, Lynnda M.; Wohlheiter, Karen

2011-01-01

Objective Using a mixed model design, this study examined the effects of interactive versus passive distraction on healthy preschool-aged children’s cold pressor pain tolerance. Methods Sixty-one children aged 3–5 years were randomly assigned to one of the following: interactive distraction, passive distraction, or no distraction control. Participants underwent a baseline cold pressor trial followed by interactive distraction trial, passive distraction trial, or second baseline trial. One or two additional trials followed. Children originally assigned to distraction received the alternate distraction intervention. Controls participated in both interactive and passive distraction trials in counterbalanced order. Results Participants showed significantly higher pain tolerance during both interactive and passive distraction relative to baseline. The two distraction conditions did not differ. Conclusions Interactive and passive video game distraction appear to be effective for preschool-aged children during laboratory pain exposure. Future studies should examine whether more extensive training would enhance effects of interactive video game distraction. PMID:21278378

The Globalization of Pediatric Research: An Analysis of Clinical Trials Completed for Pediatric Exclusivity

PubMed Central

Pasquali, Sara K.; Burstein, Danielle S.; Benjamin, Daniel K.; Smith, P. Brian; Li, Jennifer S.

2010-01-01

Background Recent studies have examined the globalization of clinical research. These studies focused on adult trials, and the globalization of pediatric research has not been examined to date. We evaluated the setting of published studies conducted under the US Pediatric Exclusivity Program, which provides economic incentives to pharmaceutical companies to conduct drug studies in children. Methods Published studies containing the main results of trials conducted from 1998–2007 under the Pediatric Exclusivity Provision were included. Data were extracted from each study and described, including the therapeutic area of drug studied, number of patients enrolled, number of sites, and location where the study was conducted, if reported. Results Overall, 174 trials were included (sample size 8–27,065 patients); 9% did not report any information regarding the location or number of sites where the study was conducted. Of those that did report this information, 65% were conducted in at least one country outside the US, and 11% did not have any sites in the US. Fifty-four different countries were represented and 38% of trials enrolled patients in at least one site located in a developing/transition country, including more than one third of infectious disease, cardiovascular, and allergy/immunology trials. Conclusions The majority of published pediatric trials conducted under the Pediatric Exclusivity Provision included sites outside of the US, and over a third of trials enrolled patients in developing/transition countries. While there are many potential benefits to the globalization of pediatric research, this trend also raises certain scientific and ethical concerns which require further evaluation. PMID:20732941

Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.

PubMed

Perlis, Roy H; Perlis, Clifford S; Wu, Yelena; Hwang, Cindy; Joseph, Megan; Nierenberg, Andrew A

2005-10-01

Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge. The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.

Characteristics of Misdemeanants Treated for Competency Restoration.

PubMed

Gillis, Artha; Holoyda, Brian; Newman, William J; Wilson, Machelle D; Xiong, Glen L

2016-12-01

There are an estimated 60,000 evaluations annually for competence to stand trial for felony indictments and likely more for misdemeanor indictments. Thus, there is an increasing interest in determining factors associated with a defendant's likelihood of being restored to competence to stand trial. Although previous studies have found that a misdemeanor charge predicts significantly less likelihood of restoration of competence when compared with felony charges, states typically allow treatment facilities less time to restore misdemeanor defendants than felony defendants. As there are no studies examining factors associated with restoration of competence to stand trial for misdemeanor defendants, separately from felony defendants, we conducted a retrospective study to examine demographic, clinical, and forensic characteristics associated with restoration of competence to stand trial of misdemeanor defendants. Almost 70 percent of defendants regained competence to stand trial during the study period. When restorable, defendants regained competence in less than three weeks, on average, which addresses a current question in the field regarding time limits for restoration of competence to stand trial. Single marital status and length of stay in the treatment facility during restoration of competence to stand trial were significantly associated with restorability. States may consider such factors when developing and reviewing time limit policies in consideration of the Jackson v. Indiana ruling and when designing interventions aimed at restoring competence to stand trial to misdemeanor defendants in a cost-efficient manner. © 2016 American Academy of Psychiatry and the Law.

Path Analysis Examining Self-Efficacy and Decision-Making Performance on a Simulated Baseball Task

ERIC Educational Resources Information Center

Hepler, Teri J.; Feltz, Deborah L.

2012-01-01

The purpose of this study was to examine the relationship between decision-making self-efficacy and decision-making performance in sport. Undergraduate students (N = 78) performed 10 trials of a decision-making task in baseball. Self-efficacy was measured before performing each trial. Decision-making performance was assessed by decision speed and…

A Randomized Effectiveness Trial of Brief Parent Training: Six-Month Follow-Up

ERIC Educational Resources Information Center

Kjøbli, John; Bjørnebekk, Gunnar

2013-01-01

Objective: To examine the follow-up effectiveness of brief parent training (BPT) for children with emerging or existing conduct problems. Method: With the use of a randomized controlled trial and parent and teacher reports, this study examined the effectiveness of BPT compared to regular services 6 months after the end of the intervention.…

Association Between Flexible Duty Hour Policies and General Surgery Resident Examination Performance: A Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial Analysis.

PubMed

Blay, Eddie; Hewitt, D Brock; Chung, Jeanette W; Biester, Thomas; Fiore, James F; Dahlke, Allison R; Quinn, Christopher M; Lewis, Frank R; Bilimoria, Karl Y

2017-02-01

Concerns persist about the effect of current duty hour reforms on resident educational outcomes. We investigated whether a flexible, less-restrictive duty hour policy (Flexible Policy) was associated with differential general surgery examination performance compared with current ACGME duty hour policy (Standard Policy). We obtained examination scores on the American Board of Surgery In-Training Examination, Qualifying Examination (written boards), and Certifying Examination (oral boards) for residents in 117 general surgery residency programs that participated in the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial. Using bivariate analyses and regression models, we compared resident examination performance across study arms (Flexible Policy vs Standard Policy) for 2015 and 2016, and 1 year of the Qualifying Examination and Certifying Examination. Adjusted analyses accounted for program-level factors, including the stratification variable for randomization. In 2016, FIRST trial participants were 4,363 general surgery residents. Mean American Board of Surgery In-Training Examination scores for residents were not significantly different between study groups (Flexible Policy vs Standard Policy) overall (Flexible Policy: mean [SD] 502.6 [100.9] vs Standard Policy: 502.7 [98.6]; p = 0.98) or for any individual postgraduate year level. There was no difference in pass rates between study arms for either the Qualifying Examination (Flexible Policy: 90.4% vs Standard Policy: 90.5%; p = 0.99) or Certifying Examination (Flexible Policy: 86.3% vs Standard Policy: 88.6%; p = 0.24). Results from adjusted analyses were consistent with these findings. Flexible, less-restrictive duty hour policies were not associated with differences in general surgery resident performance on examinations during the FIRST Trial. However, more years under flexible duty hour policies might be needed to observe an effect. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Recruiting Unmotivated Smokers into a Smoking Induction Trial

ERIC Educational Resources Information Center

Harris, Kari Jo; Bradley-Ewing, Andrea; Goggin, Kathy; Richter, Kimber P.; Patten, Christi; Williams, Karen; Lee, Hyoung S.; Staggs, Vincent S.; Catley, Delwyn

2016-01-01

Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult…

A meta-analysis of mammographic screening with and without clinical breast examination

PubMed Central

Hamashima, Chisato; Ohta, Koji; Kasahara, Yoshio; Katayama, Takafumi; Nakayama, Tomio; Honjo, Satoshi; Ohnuki, Koji

2015-01-01

Mammographic screening with clinical breast examination has been recommended in Japan since 2000. Although mammographic screening without clinical breast examination has not been recommended, its introduction is anticipated. The efficacies of mammographic screening with and without clinical breast examination were evaluated based on the results of randomized controlled trials. PubMed and other databases for studies published between 1985 and 2014 were searched. The study design was limited to randomized controlled trials to evaluate mortality reduction from breast cancer. Five studies were eligible for meta-analysis of mammographic screening without clinical breast examination. The relative risk for women aged 40–74 years was 0.75 (95% confidence interval, 0.67–0.83). Three studies evaluated the efficacy of mammographic screening with clinical breast examination. The relative risk for women aged 40–64 years was 0.87 (95% confidence interval, 0.77–0.98). The number needed to invite was always lower in mammographic screening without clinical breast examination than in mammographic screening with clinical breast examination. In both screening methods, the number needed to invite was higher in women aged 40–49 years than in women aged 50–70 years. These results suggest that mammographic screening without clinical breast examination can afford higher benefits to women aged 50 years and over. Although evidence of the efficacy of mammographic screening without clinical breast examination was confirmed based on the results of the randomized controlled trials, a Japanese study is needed to resolve local problems. PMID:25959787

Interventions for increasing fruit and vegetable consumption in children aged five years and under.

PubMed

Hodder, Rebecca K; Stacey, Fiona G; Wyse, Rebecca J; O'Brien, Kate M; Clinton-McHarg, Tara; Tzelepis, Flora; Nathan, Nicole K; James, Erica L; Bartlem, Kate M; Sutherland, Rachel; Robson, Emma; Yoong, Sze Lin; Wolfenden, Luke

2017-09-25

Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases, including cardiovascular disease. To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase Classic and Embase to identify eligible trials on 30 September 2016. We searched CINAHL and PsycINFO in July 2016, Proquest Dissertations and Theses in November 2016 and three clinical trial registers in November 2016 and June 2017. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included studies to identify further potentially relevant trials. We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. Two review authors independently extracted data and assessed the risks of bias of included studies; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures.We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. We included 50 trials with 137 trial arms and 10,267 participants. Thirty trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Eleven trials examined the impact of parent nutrition education in increasing child fruit and vegetable intake. Eight studies examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. One study examined the effect of a nutrition intervention delivered to children in increasing child fruit and vegetable intake.Thirteen of the 50 included trials were judged as free from high risks of bias across all domains; performance, detection and attrition bias were the most common domains judged at high risk of bias of remaining studies.Meta-analysis of trials examining child-feeding practices versus no intervention revealed a positive effect on child vegetable consumption (SMD 0.38, 95% CI 0.15 to 0.61; n = 1509; 11 studies; very low-quality evidence), equivalent to a mean difference of 4.03 grams of vegetables. There were no short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.11, 95% CI -0.05 to 0.28; n = 3023; 10 studies; very low-quality evidence) or multicomponent interventions versus no intervention (SMD 0.28, 95% CI -0.06 to 0.63; n = 1861; 4 studies; very low-quality evidence).Insufficient data were available to assess long-term effectiveness, cost effectiveness and unintended adverse consequences of interventions.Studies reported receiving governmental or charitable funds, except for two studies reporting industry funding. Despite identifying 50 eligible trials of various intervention approaches, the evidence for how to increase fruit and vegetable consumption of children remains sparse. There was very low-quality evidence child-feeding practice interventions are effective in increasing vegetable consumption of children aged five years and younger, however the effect size was very small and long-term follow-up is required. There was very low-quality evidence that parent nutrition education and multicomponent interventions are not effective in increasing fruit and vegetable consumption of children aged five years and younger. All findings should be considered with caution, given most included trials could not be combined in meta-analyses. Given the very low-quality evidence, future research will very likely change estimates and conclusions. Such research should adopt more rigorous methods to advance the field.This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

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

PubMed Central

2014-01-01

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

Developmental Change in Proactive Interference.

ERIC Educational Resources Information Center

Kail, Robert

2002-01-01

Two studies examined age-related change in proactive interference from previously learned material. The meta-analysis of 26 studies indicated that proactive interference decreased with age. The cross-sectional study found that third through sixth graders' and college students' recall was accurate on Trial 1, but became less so over Trials 2…

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.

PubMed

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-11-09

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

PubMed Central

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-01-01

Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials. PMID:19900273

Modeling behavioral reactivity to losses and rewards on the Balloon Analogue Risk Task (BART): moderation by alcohol problem severity.

PubMed

Ashenhurst, James R; Bujarski, Spencer; Jentsch, J David; Ray, Lara A

2014-08-01

The relationship between risk-taking behavior and substance dependence has proven to be complex, particularly when examining across participants expressing a range of substance use problem severity. While main indices of risk-taking in the Balloon Analogue Risk Task (BART) positively associate with problematic alcohol use in adolescent populations (e.g., MacPherson, Magidson, Reynolds, Kahler, & Lejuez, 2010), several studies have observed a negative relationship when examining behavior within adult substance using populations (Ashenhurst, Jentsch, & Ray, 2011; Campbell, Samartgis, & Crowe, 2013). To examine potential mechanisms that underlie this negative relationship, we implemented multilevel regression models on trial-by-trial BART data gathered from 295 adult problem drinkers. These models accounted for participant behavior on trials following balloon bursts or cash outs as indices of loss and reward reactivity, respectively, and included control variables including age, IQ, and individual delay discounting rate. Results revealed that individual trial pumping was significantly predicted by trial number, and by whether or not the previous trial was a big burst or a big cash out (i.e., large magnitude of potential gains) in a manner consistent with a "near-miss" effect. Furthermore, severity of alcohol problems moderated the effect of a previous trial big burst, but not of a big cash out, on subsequent trial behavior such that those with greater severity demonstrated relative insensitivity to this "near-miss" effect. These results extend previous studies suggesting that alcohol abusers are less risky on the BART by specifying a mechanism underlying this pattern, namely, diminished reactivity to large magnitude losses.

Impact of Clinical Trial Results on the Temporal Trends of Carotid Endarterectomy and Stenting From 2002 to 2014

PubMed Central

Hussain, Mohamad A.; Mamdani, Muhammad; Tu, Jack V.; Saposnik, Gustavo; Khoushhal, Zeyad; Aljabri, Badr; Verma, Subdoh

2016-01-01

Background and Purpose— Randomized trials provide conflicting data for the efficacy of carotid-artery stenting compared with endarterectomy. The purpose of this study was to examine the impact of conflicting clinical trial publications on the utilization rates of carotid revascularization procedures. Methods— We conducted a population-level time-series analysis of all individuals who underwent carotid endarterectomy and stenting in Ontario, Canada (2002–2014). The primary analysis examined temporal changes in the rates of carotid revascularization procedures after publications of major randomized trials. Secondary analyses examined changes in overall and age, sex, carotid-artery symptom, and operator specialty–specific procedure rates. Results— A total of 16 772 patients were studied (14 394 endarterectomy [86%]; 2378 stenting [14%]). The overall rate of carotid revascularization decreased from 6.0 procedures per 100 000 individuals ≥40 years old in April 2002 to 4.3 procedures in the first quarter of 2014 (29% decrease; P<0.001). The rate of endarterectomy decreased by 36% (P<0.001), whereas the rate of carotid-artery stenting increased by 72% (P=0.006). We observed a marked increase (P=0.01) in stenting after publication of the SAPPHIRE trial (Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy) in 2004, whereas stenting remained relatively unchanged after subsequent randomized trials published in 2006 (P=0.11) and 2010 (P=0.34). In contrast, endarterectomy decreased after trials published in 2006 (P=0.04) and 2010 (P=0.005). Conclusions— Although the overall rates of carotid revascularization and endarterectomy have fallen since 2002, the rate of carotid-artery stenting has risen since the publication of stenting-favorable SAPPHIRE trial. Subsequent conflicting randomized trials were associated with a decreasing rate of carotid endarterectomy. PMID:27834754

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

PubMed

Etzioni, Ruth; Gulati, Roman; Cooperberg, Matt R; Penson, David M; Weiss, Noel S; Thompson, Ian M

2013-04-01

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

PubMed

Viecelli, Andrea K; Pascoe, Elaine; Polkinghorne, Kevan R; Hawley, Carmel; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Heritier, Stephane; Kerr, Peter G; Mori, Trevor A; Robertson, Amanda; Seong, Hooi L; Irish, Ashley B

2015-06-27

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes.

PubMed

Hausenblas, Heather Ann; Heekin, Kacey; Mutchie, Heather Lee; Anton, Stephen

2015-07-01

Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes. Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)." Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome. The methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression). Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior. Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.

Effect of study partner on the conduct of Alzheimer disease clinical trials

PubMed Central

Raman, Rema; Ernstrom, Karin; Aisen, Paul; Karlawish, Jason

2013-01-01

Objective: Alzheimer disease (AD) dementia clinical trials require 2 participants: a patient and a study partner. We assessed the prevalence of study partner types and how these types associate with patient-related outcome measures. Methods: Retrospective analyses of 6 Alzheimer’s Disease Cooperative Study (ADCS) randomized clinical trials were conducted. Study partners were categorized as spouse, adult child, or other. Prevalence of study partner type and associations between study partner type and trial outcomes including study completion and placebo decline on the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–cognitive subscale, the Clinical Dementia Rating scale Sum of the Boxes score, and the ADCS–Activities of Daily Living were examined. Results: More participants (67%) enrolled with spouses than adult children (26%) or other study partners (7%). Participants with spouse partners had a lower dropout rate (25%) than those with adult child (32%) or other study partners (34%); only the difference vs others was statistically significant. Participants with adult child and other partners randomized to placebo performed worse at baseline than those with spouse partners on the ADCS–Activities of Daily Living (p = 0.04), but were not different at 18 months. There were no differences at baseline for the Mini-Mental State Examination, Clinical Dementia Rating scale Sum of the Boxes score, or Alzheimer’s Disease Assessment Scale–cognitive subscale. In multivariate models of the rates of change over time among placebo participants, no differences among study partner groups reached statistical significance. Conclusions: Patients with nonspouse caregivers less frequently participate in AD dementia trials. Increased enrollment of AD patients with nonspouse caregivers may require additional recruitment and retention strategies. PMID:23255824

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics, and Their Environment

DTIC Science & Technology

2011-07-01

cancer clinical trials, attitudes and knowledge about such trials, and barriers to and facilitators of participation, b) Conduct a self-administered...facilitate or hinder participation in prostate cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of...cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of prostate trials and sites, and broader community

Evidence for sample selection effect and Hawthorne effect in behavioural HIV prevention trial among young women in a rural South African community

PubMed Central

Pettifor, Audrey; Twine, Rhian; Hughes, James P; Gomez-Olive, F Xavier; Wagner, Ryan G; Sulaimon, Afolabi; Tollman, Stephen; Selin, Amanda; MacPhail, Catherine; Kahn, Kathleen

2018-01-01

Objectives We examined the potential influence of both sample selection effects and Hawthorne effects in the behavioural HIV Prevention Trial Network 068 study, designed to examine whether cash transfers conditional on school attendance reduce HIV acquisition in young South African women. We explored whether school enrolment among study participants differed from the underlying population, and whether differences existed at baseline (sample selection effect) or arose during study participation (Hawthorne effect). Methods We constructed a cohort of 3889 young women aged 11–20 years using data from the Agincourt Health and socio-Demographic Surveillance System. We compared school enrolment in 2011 (trial start) and 2015 (trial end) between those who did (n=1720) and did not (n=2169) enrol in the trial. To isolate the Hawthorne effect, we restricted the cohort to those enrolled in school in 2011. Results In 2011, trial participants were already more likely to be enrolled in school (99%) compared with non-participants (93%). However, this association was attenuated with covariate adjustment (adjusted risk difference (aRD) (95% CI): 2.9 (− 0.7 to 6.5)). Restricting to those enrolled in school in 2011, trial participants were also more likely to be enrolled in school in 2015 (aRD (95% CI): 4.9 (1.5 to 8.3)). The strength of associations increased with age. Conclusions Trial participants across both study arms were more likely to be enrolled in school than non-participants. Our findings suggest that both sample selection and Hawthorne effects may have diminished the differences in school enrolment between study arms, a plausible explanation for the null trial findings. The Hawthorne-specific findings generate hypotheses for how to structure school retention interventions to prevent HIV. PMID:29326192

Neuroimaging study of sex differences in the neuropathology of cocaine abuse.

PubMed

Li, Chiang-shan Ray; Kemp, Kathleen; Milivojevic, Verica; Sinha, Rajita

2005-09-01

Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences. This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers. We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women. The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials. The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.

The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

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

Ataman, Ozlem U., E-mail: ouataman@hotmail.com; Sambrook, Sally J.; Wilks, Chris

2012-11-15

Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, andmore » PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed.« less

Examining implementation of a patient activation and self-management intervention within the context of an effectiveness trial.

PubMed

Ault-Brutus, Andrea; Lee, Catherine; Singer, Sara; Allen, Michele; Alegría, Margarita

2014-11-01

This qualitative study examines factors important for delivering a patient activation/self-management intervention in 13 mental health clinics within the context of an effectiveness trial to inform understanding of real-world implementation. Eighteen key personnel were interviewed about the following factors relative to the intervention and its delivery: alignment with organization values/patient needs; buy-in/support from leaders and providers; roles played by leaders and key personnel; and availability of organizational resources. Where supportive, these factors facilitated the delivery of the intervention; elsewhere, they presented as impediments. Findings from this study could help anticipate challenges to implementation that could be examined in a full-scale implementation study.

Blocking, unblocking, and overexpectation in autoshaping with pigeons.

PubMed

Khallad, Y; Moore, J

1996-05-01

Three experiments used pigeons in an autoshaping procedure and a single-subject design to examine compound stimulus control in classical conditioning. Experiment 1 examined the blocking effect, and Experiment 2 examined the unblocking effect. In both experiments, response-independent food was first delivered intermittently in the presence of one distinctively colored houselight but not another. Then, conventional autoshaping trials were carried out in the presence of each houselight. In Experiment 1, the keylight readily elicited responding in the presence of the houselight that had been negatively correlated with food, but not in the presence of the houselight that had been positively correlated with food. In Experiment 2, the keylight readily elicited responding in the presence of the houselight positively correlated with food, but only when the amount of food used on the autoshaping trials was either greater or less than that previously delivered in the presence of the houselight. Experiment 3 examined the overexpectation effect. Conventional autoshaping trials were first carried out by presenting each of two keylights individually. Then, additional autoshaping trials were carried out by presenting the two keylights as a compound, with either the same amount of food or a greater amount of food per trial. Finally, the keylights were retested by again presenting them individually. The number of responses per trial elicited by the keylights decreased when the amount of food used in compound trials was the same as that used in individual trials. However, the number of responses per trial remained approximately the same when the amount of food used in compound trials was greater than that used in individual trials. Taken together, the results of the three experiments demonstrate (a) the generality of the blocking, unblocking, and overexpectation effects by virtue of their extension to appetitive unconditioned stimuli; (b) the suitability of pigeons as subjects and autoshaping as a procedure for studying classical conditioning; and (c) the appropriateness of single-subject designs.

Blocking, unblocking, and overexpectation in autoshaping with pigeons

PubMed Central

Khallad, Yacoub; Moore, Jay

1996-01-01

Three experiments used pigeons in an autoshaping procedure and a single-subject design to examine compound stimulus control in classical conditioning. Experiment 1 examined the blocking effect, and Experiment 2 examined the unblocking effect. In both experiments, response-independent food was first delivered intermittently in the presence of one distinctively colored houselight but not another. Then, conventional autoshaping trials were carried out in the presence of each houselight. In Experiment 1, the keylight readily elicited responding in the presence of the houselight that had been negatively correlated with food, but not in the presence of the houselight that had been positively correlated with food. In Experiment 2, the keylight readily elicited responding in the presence of the houselight positively correlated with food, but only when the amount of food used on the autoshaping trials was either greater or less than that previously delivered in the presence of the houselight. Experiment 3 examined the overexpectation effect. Conventional autoshaping trials were first carried out by presenting each of two keylights individually. Then, additional autoshaping trials were carried out by presenting the two keylights as a compound, with either the same amount of food or a greater amount of food per trial. Finally, the keylights were retested by again presenting them individually. The number of responses per trial elicited by the keylights decreased when the amount of food used in compound trials was the same as that used in individual trials. However, the number of responses per trial remained approximately the same when the amount of food used in compound trials was greater than that used in individual trials. Taken together, the results of the three experiments demonstrate (a) the generality of the blocking, unblocking, and overexpectation effects by virtue of their extension to appetitive unconditioned stimuli; (b) the suitability of pigeons as subjects and autoshaping as a procedure for studying classical conditioning; and (c) the appropriateness of single-subject designs. PMID:16812810

An Examination of the ECST-R as a Screen for Feigned Incompetency to Stand Trial

ERIC Educational Resources Information Center

Rogers, Richard; Jackson, Rebecca L.; Sewell, Kenneth W.; Harrison, Kimberly S.

2004-01-01

Psychological assessments of competency-to-stand-trial (CST) referrals must consider whether the defendants' impairment is genuine or feigned. This study addressed feigning on the Evaluation of Competency to Stand Trial--Revised (ECST-R), a standardized interview designed for assessing dimensions of CST and screening for feigned CST. In…

The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials.

PubMed

Pase, Matthew P; Kean, James; Sarris, Jerome; Neale, Chris; Scholey, Andrew B; Stough, Con

2012-07-01

Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans. A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors. Relevant trials were objectively assessed for methodological quality. The subjects studied were adult humans without dementia or significant cognitive impairment. B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods. Any validated cognitive test, whether a primary or secondary outcome. Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300-450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of enhancement in any other cognitive domains. There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied dosages and across different extracts.

Train the Trainer Effectiveness Trials of Behavioral Intervention for Individuals with Autism: A Systematic Review

ERIC Educational Resources Information Center

Shire, Stephanie Yoshiko; Kasari, Connie

2014-01-01

This systematic review examines train the trainer (TTT) effectiveness trials of behavioral interventions for individuals with autism spectrum disorder (ASD). Published methodological quality scales were used to assess studies including participant description, research design, intervention, outcomes, and analysis. Twelve studies including 9 weak…

Predictors of Adherence in the Women’s Health Initiative Calcium and Vitamin D Trial

PubMed Central

Brunner, R.; Dunbar-Jacob, J.; LeBoff, M. S.; Granek, I.; Bowen, D.; Snetselaar, L. G.; Shumaker, S. A.; Ockene, J.; Rosal, M.; Wactawski-Wende, J.; Cauley, J.; Cochrane, B.; Tinker, L.; Jackson, R.; Wang, C. Y.; Wu, L.

2010-01-01

The authors analyzed data from the Women’s Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50–79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking ≥ 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial. PMID:19064373

Recruitment strategies in two Reproductive Medicine Network infertility trials

PubMed Central

Usadi, Rebecca S.; Diamond, Michael P.; Legro, Richard S.; Schlaff, William D.; Hansen, Karl R.; Casson, Peter; Christman, Gregory; Bates, G. Wright; Baker, Valerie; Seungdamrong, Aimee; Rosen, Mitchell P.; Lucidi, Scott; Thomas, Tracey; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Alvero, Ruben

2016-01-01

Background Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. Methods We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. Results 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. Conclusions Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment. PMID:26386293

Recruitment strategies in two reproductive medicine network infertility trials.

PubMed

Usadi, Rebecca S; Diamond, Michael P; Legro, Richard S; Schlaff, William D; Hansen, Karl R; Casson, Peter; Christman, Gregory; Wright Bates, G; Baker, Valerie; Seungdamrong, Aimee; Rosen, Mitchell P; Lucidi, Scott; Thomas, Tracey; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Alvero, Ruben

2015-11-01

Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was the use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment. Copyright © 2015 Elsevier Inc. All rights reserved.

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions

PubMed Central

Farmer, Sybil; Pandyan, Anand; Chockalingam, Nachiappan

2018-01-01

Background Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world’s population need a prosthesis or orthosis. Objective The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. Methods Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. Results A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. Conclusions At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness. PMID:29538382

Examining longitudinal stimulant use and treatment attendance as parallel outcomes in two contingency management randomized clinical trials

PubMed Central

McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

2015-01-01

The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one ‘parallel outcomes’ model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β = 0.060, p < 0.05). In the second trial, CM predicted negative urinalysis (−UA) over the 12-week treatment period (β = 0.069, p < 0.05). In both trials, there was a significant, positive relationship between attendance and −UA submission, but in the first trial a −UA at both baseline and over time was related to attendance over time (r = 0.117; r = 0.013, respectively) and in the second trial, a −UA submission at baseline was associated with increased attendance over time (r = 0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This ‘indirect reinforcement’ between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717

Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

PubMed

McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

2016-02-01

The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of a Motivational Interviewing-Informed Strategy in Group Orientations to Improve Retention and Intervention Attendance in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Xiao, Lan; Lv, Nan; Rosas, Lisa G.; Karve, Shweta; Luna, Veronica; Jameiro, Elizabeth; Wittels, Nancy; Ma, Jun

2016-01-01

High retention and treatment adherence are essential to ensure the quality of evidence from clinical trials. Strategies for improving these have been explored but actual rates in lifestyle intervention trials indicate challenges. This study examined the use of a motivational interviewing-informed strategy during interactive group orientations…

A case study of SMART attributes: a qualitative assessment of generalizability, retention rate, and trial quality.

PubMed

Moodie, Erica E M; Karran, James C; Shortreed, Susan M

2016-05-14

Personalizing medical care is becoming increasingly popular, particularly mental health care. There is growing interest in formalizing medical decision making based on evolving patient symptoms in an evidence-based manner. To determine optimal sequencing of treatments, the sequences themselves must be studied; this may be accomplished by using a sequential multiple assignment randomized trial (SMART). It has been hypothesized that SMART studies may improve participant retention and generalizability. We examine the hypotheses that SMART studies are more generalizable and have better retention than traditional randomized clinical trials via a case study of a SMART study of antipsychotic medications. We considered the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study, comparing the trial participant characteristics and overall retention to those of comparable trials found via a review of all related trials conducted from 2000 onwards. A MEDLINE search returned 6435 results for primary screening; ultimately, 48 distinct trials were retained for analysis. The study population in CATIE was similar to, although perhaps less symptomatic than, the study populations of traditional randomized clinical trials (RCTs), suggesting no large gains in generalizability despite the pragmatic nature of the trial. However, CATIE did see good month-by-month retention. SMARTs offer the possibility of studying treatment sequences in a way that a series of traditional RCTs cannot. SMARTs may offer improved retention; however, this case study did not find evidence to suggest greater generalizability using this trial design. ClinicalTrials.gov NCT00014001 . Registered on 6 April 2001.

Examining Implementation of a Patient Activation and Self-management Intervention Within the Context of an Effectiveness Trial

PubMed Central

Lee, Catherine; Singer, Sara; Allen, Michele; Alegría, Margarita

2014-01-01

This qualitative study examines factors important for delivering a patient activation/self-management intervention in 13 mental health clinics within the context of an effectiveness trial to inform understanding of real-world implementation. Eighteen key personnel were interviewed about the following factors relative to the intervention and its delivery: alignment with organization values/patient needs; buy-in/support from leaders and providers; roles played by leaders and key personnel; and availability of organizational resources. Where supportive, these factors facilitated the delivery of the intervention; elsewhere, they presented as impediments. Findings from this study could help anticipate challenges to implementation that could be examined in a full-scale implementation study. PMID:24202066

A Randomized Trial of Two Promising Computer-Based Interventions for Students with Attention Difficulties

ERIC Educational Resources Information Center

Rabiner, David L.; Murray, Desiree W.; Skinner, Ann T; Malone, Patrick S.

2010-01-01

Few studies have examined whether attention can be improved with training, even though attention difficulties adversely affect academic achievement. The present study was a randomized-controlled trial evaluating the impact of Computerized Attention Training (CAT) and Computer Assisted Instruction (CAI) on attention and academic performance in 77…

U.S. Virtual School Trial Period and Course Completion Policy Study

ERIC Educational Resources Information Center

Hawkins, Abigail; Barbour, Michael K.

2010-01-01

Variation in policies virtual schools use to calculate course completion and retention rates impacts the comparability of these quality metrics. This study surveyed 159 U.S. virtual schools examining the variability in trial period and course completion policies--two policies that affect course completion rates. Of the 86 respondents, almost 70%…

DESIGN OF A MTBE REMEDIATION TECHNOLOGY EVALUATION

EPA Science Inventory

This study examines the intrinsic variability of dissolved MTBE concentrations in ground water during the course of a pilot-scale bioremedial technology trial in Port Hueneme, California. A pre-trial natural gradient tracer experiment using bromide was conducted in an anaerobic t...

Baseline Characteristics and Generalizability of Participants in an Internet Smoking Cessation Randomized Trial.

PubMed

Cha, Sarah; Erar, Bahar; Niaura, Raymond S; Graham, Amanda L

2016-10-01

The potential for sampling bias in Internet smoking cessation studies is widely recognized. However, few studies have explicitly addressed the issue of sample representativeness in the context of an Internet smoking cessation treatment trial. The purpose of the present study is to examine the generalizability of participants enrolled in a randomized controlled trial of an Internet smoking cessation intervention using weighted data from the National Health Interview Survey (NHIS). A total of 5290 new users on a smoking cessation website enrolled in the trial between March 2012 and January 2015. Descriptive statistics summarized baseline characteristics of screened and enrolled participants, and multivariate analysis examined predictors of enrollment. Generalizability analyses compared demographic and smoking characteristics of trial participants to current smokers in the 2012-2014 waves of NHIS (n = 19,043) and to an NHIS subgroup based on Internet use and cessation behavior (n = 3664). Effect sizes were obtained to evaluate the magnitude of differences across variables. Predictors of study enrollment were age, gender, race, education, and motivation to quit. Compared to NHIS smokers, trial participants were more likely to be female, college educated, and daily smokers and to have made a quit attempt in the past year (all effect sizes 0.25-0.60). In comparisons with the NHIS subgroup, differences in gender and education were attenuated, while differences in daily smoking and smoking rate were amplified. Few differences emerged between Internet trial participants and nationally representative samples of smokers, and all were in expected directions. This study highlights the importance of assessing generalizability in a focused and specific manner. CLINICALTRIALS.GOV: #NCT01544153.

Individual personality differences in Port Jackson sharks Heterodontus portusjacksoni.

PubMed

Byrnes, E E; Brown, C

2016-08-01

This study examined interindividual personality differences between Port Jackson sharks Heterodontus portusjacksoni utilizing a standard boldness assay. Additionally, the correlation between differences in individual boldness and stress reactivity was examined, exploring indications of individual coping styles. Heterodontus portusjacksoni demonstrated highly repeatable individual differences in boldness and stress reactivity. Individual boldness scores were highly repeatable across four trials such that individuals that were the fastest to emerge in the first trial were also the fastest to emerge in subsequent trials. Additionally, individuals that were the most reactive to a handling stressor in the first trial were also the most reactive in a second trial. The strong link between boldness and stress response commonly found in teleosts was also evident in this study, providing evidence of proactive-reactive coping styles in H. portusjacksoni. These results demonstrate the presence of individual personality differences in sharks for the first time. Understanding how personality influences variation in elasmobranch behaviour such as prey choice, habitat use and activity levels is critical to better managing these top predators which play important ecological roles in marine ecosystems. © 2016 The Fisheries Society of the British Isles.

Medically induced hypertension, hypervolaemia and haemodilution for the treatment and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage: systematic review.

PubMed

Loan, James J M; Wiggins, Anthony N; Brennan, Paul M

2018-01-17

Arterial vasospasm is a major cause of death and long-term disability following subarachnoid haemorrhage (SAH). The use of medically induced hypertension, hypervolaemia and/or haemodilution is widely practiced for prophylaxis and treatment of vasospasm following SAH. We aimed to determine if the quality of available research is adequate to inform use of haemodynamic management strategies to prevent or treat vasospasm following SAH. Individual searches of the following databases were conducted: The Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and cohort studies comparing any element or combination thereof: medically induced hypertension, hypervolaemia, and haemodilution were included. Data were extracted using standardised proformas and risk of bias assessed using a domain-based risk of bias assessment tool. 348 study reports were identified by our literature search. Eight studies were included, three of which examined both volume expansion and medically induced hypertension. Three randomised clinical trials and two cohort studies examining prophylactic volume expansion were included. Two trials of prophylactic medically induced hypertension and two cohort studies were included. One trial and one cohort study of medically induced hypertension for treatment of established vasospasm was included. These trials demonstrated no significant difference in any of the clinical outcome measures studied. No trials of blood transfusion were included. There is currently insufficient evidence to determine the efficacy or non-efficacy of intravenous volume expansion, medically induced hypertension or blood transfusion for the treatment or prophylaxis of vasospasm following SAH. All of these approaches have been associated with adverse events, of unclear incidence. The current evidence base therefore cannot be used to reliably inform clinical practice. This is a priority for further research.

Smartphone-based ecological momentary assessment and intervention in a coping-focused intervention for hearing voices (SAVVy): study protocol for a pilot randomised controlled trial.

PubMed

Bell, Imogen H; Fielding-Smith, Sarah F; Hayward, Mark; Rossell, Susan L; Lim, Michelle H; Farhall, John; Thomas, Neil

2018-05-02

Smartphone-based ecological momentary assessment and intervention (EMA/I) show promise for enhancing psychological treatments for psychosis. EMA has the potential to improve assessment and formulation of experiences which fluctuate day-to-day, and EMI may be used to prompt use of therapeutic strategies in daily life. The current study is an examination of these capabilities in the context of a brief, coping-focused intervention for distressing voice hearing experiences. This is a rater-blinded, pilot randomised controlled trial comparing a four-session intervention in conjunction with use of smartphone EMA/I between sessions, versus treatment-as-usual. The recruitment target is 34 participants with persisting and distressing voice hearing experiences, recruited through a Voices Clinic based in Melbourne, Australia, and via wider advertising. Allocation will be made using minimisation procedure, balancing of the frequency of voices between groups. Assessments are completed at baseline and 8 weeks post-baseline. The primary outcomes of this trial will focus on feasibility and acceptability of the intervention and trial methodology, with secondary outcomes examining preliminary clinical effects related to overall voice severity, the emotional and functional impact of the voices, and emotional distress. This study offers a highly novel examination of specific smartphone capabilities and their integration with traditional psychological treatment for distressing voices. Such technology has potential to enhance psychological interventions and promote adaptation to distressing experiences. Australian New Zealand Clinical Trial Registry, ACTRN12617000348358 . Registered on 7 March 2017.

A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network.

PubMed

Roman, Paul M; Abraham, Amanda J; Rothrauff, Tanja C; Knudsen, Hannah K

2010-06-01

The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future.

Shedding light on research participation effects in behaviour change trials: a qualitative study examining research participant experiences.

PubMed

MacNeill, Virginia; Foley, Marian; Quirk, Alan; McCambridge, Jim

2016-01-29

The sequence of events in a behaviour change trial involves interactions between research participants and the trial process. Taking part in such a study has the potential to influence the behaviour of the participant, and if it does, this can engender bias in trial outcomes. Since participants' experience has received scant attention, the aim of this study is thus to generate hypotheses about which aspects of the conduct of behaviour change trials might matter most to participants, and thus have potential to alter subsequent behaviours and bias trial outcomes Twenty participants were opportunistically screened for a health compromising behaviour (unhealthy diet, lack of exercise, smoking or alcohol consumption) and recruited if eligible. Semi structured face to face interviews were conducted, after going through the usual processes involved in trial recruitment, baseline assessment and randomisation. Participants were given information on the contents of an intervention or control condition in a behaviour change trial, which was not actually implemented. Three months later they returned to reflect on these experiences and whether they had any effect on their behaviour during the intervening period. Data from the latter interview were analysed thematically using a modified grounded theory approach. The early processes of trial participation raised awareness of unhealthy behaviours, although most reported having had only fleeting intentions to change their behaviour as a result of taking part in this study, in the absence of interventions. However, careful examination of the accounts revealed evidence of subtle research participation effects, which varied according to the health behaviour, and its perceived social acceptability. Participants' relationships with the research study were viewed as somewhat important in stimulating thinking about whether and how to make lifestyle changes. These participants described no dramatic impacts attributable to taking part in this study. This study demonstrates the likely value of well conducted qualitative studies of subtle research participation effects, which may be particularly important to explore for alcohol. Separating unintended influences in trial participation from the effects of behaviour change interventions being evaluated therein is necessary for valid estimates of intervention effects.

Pain-Relieving Interventions for Retinopathy of Prematurity: A Meta-analysis.

PubMed

Disher, Timothy; Cameron, Chris; Mitra, Souvik; Cathcart, Kelcey; Campbell-Yeo, Marsha

2018-06-01

Retinopathy of prematurity eye examinations conducted in the neonatal intensive care. To combine randomized trials of pain-relieving interventions for retinopathy of prematurity examinations using network meta-analysis. Systematic review and network meta-analysis of Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the World Health Organization International Clinical Trials Registry Platform. All databases were searched from inception to February 2017. Abstract and title screen and full-text screening were conducted independently by 2 reviewers. Data were extracted by 2 reviewers and pooled with random effect models if the number of trials within a comparison was sufficient. The primary outcome was pain during the examination period; secondary outcomes were pain after the examination, physiologic response, and adverse events. Twenty-nine studies ( N = 1487) were included. Topical anesthetic (TA) combined with sweet taste and an adjunct intervention (eg, nonnutritive sucking) had the highest probability of being the optimal treatment (mean difference [95% credible interval] versus TA alone = -3.67 [-5.86 to -1.47]; surface under the cumulative ranking curve = 0.86). Secondary outcomes were sparsely reported (2-4 studies, N = 90-248) but supported sweet-tasting solutions with or without adjunct interventions as optimal. Limitations included moderate heterogeneity in pain assessment reactivity phase and severe heterogeneity in the regulation phase. Multisensory interventions including sweet taste is likely the optimal treatment for reducing pain resulting from eye examinations in preterm infants. No interventions were effective in absolute terms. Copyright © 2018 by the American Academy of Pediatrics.

The Efficacy of a Web-Based Screening and Brief Intervention for Reducing Alcohol Consumption Among Japanese Problem Drinkers: Protocol for a Single-Blind Randomized Controlled Trial.

PubMed

Hamamura, Toshitaka; Suganuma, Shinichiro; Takano, Ayumi; Matsumoto, Toshihiko; Shimoyama, Haruhiko

2018-05-30

The literature shows that computer-delivered interventions with personalized normative feedback can reduce problem drinking for up to 6 months in the West. Meanwhile, no studies have been conducted to examine the effects of such interventions among Japanese problem drinkers. Possible moderators associated with effectiveness of the intervention need to be also explored. The purpose of this study is to conduct a trial and examine the efficacy of a brief intervention with personal normative feedback and psychoeducation on several measures of alcohol consumption among Japanese problem drinkers. Additionally, this study will examine whether the level of alcohol use disorder and beliefs about the physical and psychological outcomes of drinking moderate the effect of the intervention on outcome measures. This study will conduct a single-blind, 2-armed randomized controlled trial. Japanese adults with an Alcohol Use Disorder Identification Test score of 8 or higher will be enrolled in the trial. Participants allocated to the intervention group will receive the intervention immediately after the baseline measurements, and participants allocated to the waitlist group will receive the intervention at the end of the trial. Outcome measures include drinking quantity, drinking frequency, and alcohol-related consequences. Follow-up assessment will take place at 1 month, 2 months, and 6 months following the baseline measurement. The authors will not know the group allocation during trial. The authors will plan to collect a sample of 600 participants. Mixed-effect analyses of variance will be used to examine the main effects of condition, the main effects of time, and the interaction effects between condition and time on outcome variables. Enrollment for the trial began on January 6, 2018 and data are expected to be available by August 2018. This study will contribute to the literature by demonstrating the efficacy of Web-based screenings and brief interventions among Japanese problem drinkers and indicating several possible moderators between the intervention and outcomes. This type of Web-based brief intervention has the possibility of being implemented in Japanese schools and workplaces as a prevention tool. UMIN Clinical Trials Registry R000034388; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000034388 (Archived by WebCite at http://www.webcitation.org/6xmOoTfTI). RR1-10.2196/10650. ©Toshitaka Hamamura, Shinichiro Suganuma, Ayumi Takano, Toshihiko Matsumoto, Haruhiko Shimoyama. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.05.2018.

Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study

PubMed Central

Glenton, Claire; Oxman, Andrew D

2009-01-01

Objective To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Design Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Data sources Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Methods Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. Results 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Conclusions Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings. PMID:19744976

Sample size and number of outcome measures of veterinary randomised controlled trials of pharmaceutical interventions funded by different sources, a cross-sectional study.

PubMed

Wareham, K J; Hyde, R M; Grindlay, D; Brennan, M L; Dean, R S

2017-10-04

Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011. A structured search of PubMed identified RCTs examining the efficacy of pharmaceutical interventions. Number of outcome measures, number of animals enrolled per trial, whether a primary outcome was identified, and the presence of a sample size calculation were extracted from the RCTs. The source of funding was identified for each trial and groups compared on the above parameters. Literature searches returned 972 papers; 86 papers comprising 126 individual trials were analysed. The median number of outcomes per trial was 5.0; there were no significant differences across funding groups (p = 0.133). The median number of animals enrolled per trial was 30.0; this was similar across funding groups (p = 0.302). A primary outcome was identified in 40.5% of trials and was significantly more likely to be stated in trials funded by a pharmaceutical company. A very low percentage of trials reported a sample size calculation (14.3%). Failure to report primary outcomes, justify sample sizes and the reporting of multiple outcome measures was a common feature in all of the clinical trials examined in this study. It is possible some of these factors may be affected by the source of funding of the studies, but the influence of funding needs to be explored with a larger number of trials. Some veterinary RCTs provide a weak evidence base and targeted strategies are required to improve the quality of veterinary RCTs to ensure there is reliable evidence on which to base clinical decisions.

Evidence that judgments of learning are causally related to study choice.

PubMed

Metcalfe, Janet; Finn, Bridgid

2008-02-01

Three experiments investigated whether study choice was directly related to judgments of learning (JOLs) by examining people's choices in cases in which JOLs were dissociated from recall. In Experiment 1, items were given either three repetitions or one repetition on Trial 1. Items given three repetitions received one on Trial 2, and those given one repetition received three on Trial 2-equating performance at the end of Trial 2, but yielding different immediate Trial 2 JOLs. Study choice followed the "illusory" JOLs. A delayed JOL condition in Experiment 2 did not show this JOL bias and neither did study choice. Finally, using a paradigm (Koriat & Bjork, 2005) in which similar JOLs are given to forward and backward associative pairs, despite much worse performance on the backward pairs, study choice again followed the mistaken JOLs. We concluded that JOLs-what people believe they know-directly influence people's study choices.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

A Systematic Review of Randomized Controlled Trials Examining the Effectiveness of Saffron (Crocus sativus L.) on Psychological and Behavioral Outcomes

PubMed Central

Hausenblas, Heather Ann; Heekin, Kacey; Mutchie, Heather Lee; Anton, Stephen

2017-01-01

Introduction Throughout the past three decades, increased scientific attention has been given to examining saffron’s (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. Saffron has been shown to improve numerous health-related physiological to psychological outcomes. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological and behavioral outcomes. Methods Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)”. Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Results Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes with respect to the following health conditions: major depressive disorder (n = 6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n = 4), and weight loss/snacking behaviors (n = 1). The data from these studies support the efficacy of saffron in improving: depressive symptoms, premenstrual symptoms, sexual function, and satiety. Conclusion Findings from initial clinical trials suggest that saffron can improve the symptoms and effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings. PMID:26165367

Study design and "evidence" in patient-oriented research.

PubMed

Concato, John

2013-06-01

Individual studies in patient-oriented research, whether described as "comparative effectiveness" or using other terms, are based on underlying methodological designs. A simple taxonomy of study designs includes randomized controlled trials on the one hand, and observational studies (such as case series, cohort studies, and case-control studies) on the other. A rigid hierarchy of these design types is a fairly recent phenomenon, promoted as a tenet of "evidence-based medicine," with randomized controlled trials receiving gold-standard status in terms of producing valid results. Although randomized trials have many strengths, and contribute substantially to the evidence base in clinical care, making presumptions about the quality of a study based solely on category of research design is unscientific. Both the limitations of randomized trials as well as the strengths of observational studies tend to be overlooked when a priori assumptions are made. This essay presents an argument in support of a more balanced approach to evaluating evidence, and discusses representative examples from the general medical as well as pulmonary and critical care literature. The simultaneous consideration of validity (whether results are correct "internally") and generalizability (how well results apply to "external" populations) is warranted in assessing whether a study's results are accurate for patients likely to receive the intervention-examining the intersection of clinical and methodological issues in what can be called a medicine-based evidence approach. Examination of cause-effect associations in patient-oriented research should recognize both the strengths and limitations of randomized trials as well as observational studies.

Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

PubMed

Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

2012-07-01

Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

Electrophysiological Activity Generated during the Implicit Association Test: A Study Using Event-Related Potentials

ERIC Educational Resources Information Center

O'Toole, Catriona; Barnes-Holmes, Dermot

2009-01-01

The Implicit Association Test (IAT) examines the differential association of 2 target concepts with 2 attribute concepts. Responding is predicted to be faster on consistent trials, when concepts that are associated in memory share a response key, than on inconsistent trials, when less associated items share a key. In the current study,…

Does Fidelity of Implementation Account for Changes in Teacher-Child Interactions in a Randomized Controlled Trial of Banking Time?

ERIC Educational Resources Information Center

LoCasale-Crouch, Jennifer; Williford, Amanda; Whittaker, Jessica; DeCoster, Jamie; Alamos, Pilar

2018-01-01

This study examined fidelity of implementation in a randomized trial of Banking Time, a classroom-based intervention intended to improve children's behavior, specifically for those at risk for developing externalizing behavior problems, through improving the quality of teacher-child interactions. The study sample comes from a randomized controlled…

Baseline Characteristics and Generalizability of Participants in an Internet Smoking Cessation Randomized Trial

PubMed Central

Cha, Sarah; Erar, Bahar; Niaura, Raymond S.; Graham, Amanda L.

2016-01-01

Background The potential for sampling bias in Internet smoking cessation studies is widely recognized. However, few studies have explicitly addressed the issue of sample representativeness in the context of an Internet smoking cessation treatment trial. Purpose To examine the generalizability of participants enrolled in a randomized controlled trial of an Internet smoking cessation intervention using weighted data from the National Health Interview Survey (NHIS). Methods A total of 5,290 new users on a smoking cessation website enrolled in the trial between March 2012–January 2015. Descriptive statistics summarized baseline characteristics of screened and enrolled participants and multivariate analysis examined predictors of enrollment. Generalizability analyses compared demographic and smoking characteristics of trial participants to current smokers in the 2012–2014 waves of NHIS (n=19,043), and to an NHIS subgroup based on Internet use and cessation behavior (n=3,664). Effect sizes were obtained to evaluate the magnitude of differences across variables. Results Predictors of study enrollment were age, gender, race, education, and motivation to quit. Compared to NHIS smokers, trial participants were more likely to be female, college educated, daily smokers, and to have made a quit attempt in the past year (all effect sizes 0.25–0.60). In comparisons with the NHIS subgroup, differences in gender and education were attenuated while differences in daily smoking and smoking rate were amplified. Conclusions Few differences emerged between Internet trial participants and nationally representative samples of smokers, and all were in expected directions. This study highlights the importance of assessing generalizability in a focused and specific manner. PMID:27283295

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.

The MATISSE study: a randomised trial of group art therapy for people with schizophrenia

PubMed Central

2010-01-01

Background Art Therapy has been promoted as a means of helping people who may find it difficult to express themselves verbally engage in psychological treatment. Group Art Therapy has been widely used as an adjunctive treatment for people with schizophrenia but there have been few attempts to examine its effects and cost effectiveness has not been examined. The MATISSE study aims to evaluate the clinical and cost effectiveness of group Art Therapy for people with schizophrenia. Method/Design The MATISSE study is a three-arm, parallel group, pragmatic, randomised, controlled trial of referral to group Art Therapy plus standard care, referral to an attention control 'activity' group plus standard care, or standard care alone. Study participants were recruited from inpatient and community-based mental health and social care services at four centres in England and Northern Ireland. Participants were aged over 18 years with a clinical diagnosis of schizophrenia, confirmed by an examination of case notes using operationalised criteria. Participants were then randomised via an independent and remote telephone randomisation service using permuted stacked blocks, stratified by site. Art Therapy and activity groups were made available to participants once a week for up to 12 months. Outcome measures were assessed by researchers masked to allocation status at 12 and 24 months after randomisation. Participants and care givers were aware which arm of the trial participants were allocated to. The primary outcomes for the study are global functioning (measured using the Global Assessment of Functioning scale) and mental health symptoms (measured using the Positive and Negative Syndrome Scale) assessed at 24 months. Secondary outcomes were assessed at 12 and 24 months and comprise levels of group attendance, social function, satisfaction with care, mental wellbeing, and costs. Discussion We believe that this is the first large scale pragmatic trial of Art Therapy for people with schizophrenia. Trial registration Current Controlled Trials ISRCTN46150447 PMID:20799930

The use of clinical trials in comparative effectiveness research on mental health

PubMed Central

Blanco, Carlos; Rafful, Claudia; Olfson, Mark

2013-01-01

Objectives A large body of research on comparative effectiveness research (CER) focuses on the use of observational and quasi-experimental approaches. We sought to examine the use of clinical trials as a tool for CER, particularly in mental health. Study Design and Setting Examination of three ongoing randomized clinical trials in psychiatry that address issues which would pose difficulties for non-experimental CER methods. Results Existing statistical approaches to non-experimental data appear insufficient to compensate for biases that may arise when the pattern of missing data cannot be properly modeled such as when there are no standards for treatment, when affected populations have limited access to treatment, or when there are high rates of treatment dropout. Conclusions Clinical trials should retain an important role in CER, particularly in cases of high disorder prevalence, large expected effect sizes, difficult to reach populations or when examining sequential treatments or stepped-care algorithms. Progress in CER in mental health will require careful consideration of appropriate selection between clinical trials and non-experimental designs and on allocation of research resources to optimally inform key treatment decisions for each individual patient. PMID:23849150

Breast Cancer Screening by Physical Examination: Randomized Trial in the Phillipines

DTIC Science & Technology

2005-10-01

J -4327 TITLE: Breast Cancer Screening by Physical Examination: Randomized Trial in the Phillipines...Examination: Randomized Trial in the 5a. CONTRACT NUMBER Phillipines 5b. GRANT NUMBER DAMD17-94- J -4327 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Grant DAMD17-94- J -4327 3 Table of

Effect of race/ethnicity on participation in HIV vaccine trials and comparison to other trials of biomedical prevention.

PubMed

Dhalla, Shayesta; Poole, Gary

2014-01-01

Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites. In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials. In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.

The relationship between perceived discomfort of static posture holding and posture holding time.

PubMed

Ogutu, Jack; Park, Woojin

2015-01-01

Few studies have investigated mathematical characteristics of the discomfort-time relationship during prolonged static posture holding (SPH) on an individual basis. Consequently, the discomfort-time relationship is not clearly understood at individual trial level. The objective of this study was to examine discomfort-time sequence data obtained from a large number of maximum-duration SPH trials to understand the perceived discomfort-posture holding time relationship at the individual SPH trial level. Thirty subjects (15 male, 15 female) participated in this study as paid volunteers. The subjects performed maximum-duration SPH trials employing 12 different wholebody static postures. The hand-held load for all the task trials was a ``generic'' box weighing 2 kg. Three mathematical functions, that is, linear, logarithmic and power functions were examined as possible mathematical models for representing individual discomfort-time profiles of SPH trials. Three different time increase patterns (negatively accelerated, linear and positively accelerated) were observed in the discomfort-time sequences data. The power function model with an additive constant term was found to adequately fit most (96.4%) of the observed discomfort-time sequences, and thus, was recommended as a general mathematical representation of the perceived discomfort-posture holding time relationship in SPH. The new knowledge on the nature of the discomfort-time relationship in SPH and the power function representation found in this study will facilitate analyzing discomfort-time data of SPH and developing future posture analysis tools for work-related discomfort control.

Standardising the reporting of outcomes in gastric cancer surgery trials: protocol for the development of a core outcome set and accompanying outcome measurement instrument set (the GASTROS study).

PubMed

Alkhaffaf, Bilal; Glenny, Anne-Marie; Blazeby, Jane M; Williamson, Paula; Bruce, Iain A

2017-08-09

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Whilst surgery is the mainstay of curative treatment, it is associated with significant risks. Surgical strategies for treating gastric cancer should be based on evidence from systematic reviews of well-designed randomised controlled trials. However, inconsistencies in the reporting of outcomes from these trials makes evidence synthesis unreliable. We present a protocol for an international consensus study to develop a standardised set of outcomes and measurement tools - a 'core outcome set' (COS) - to be used by all future trials examining therapeutic surgical interventions for gastric cancer. The GASTROS study aims to standardise the reporting of outcomes in gastric cancer surgery trials through an international consensus process of key stakeholders including health care professionals and patients. The first of three stages in the study will identify a 'long-list' of potentially important outcomes to be prioritised. These will be extracted from a systematic review of relevant academic literature and patient interviews. Stage 2 will comprise an eDelphi survey which will consider the views of patients, nurse specialists and surgeons to prioritise the most important outcomes. A meeting of stakeholder representatives will ratify the COS. Stage 3 will focus on identifying appropriate instruments to measure the prioritised outcomes by means of quality assessment of available measurement instruments and stakeholder consultation. This study aims to standardise the reporting of outcomes in future trials examining therapeutic surgical interventions for gastric cancer. It is anticipated that standardisation of outcome reporting in these surgical effectiveness trials will enhance the evidence base for clinical practice. Highlighting outcomes of greatest importance to patients will ensure that their perspectives are central to research in this field.

Shaking that icky feeling: effects of extinction and counterconditioning on disgust-related evaluative learning.

PubMed

Engelhard, Iris M; Leer, Arne; Lange, Emma; Olatunji, Bunmi O

2014-09-01

Learned disgust appears to play an important role in certain anxiety disorders, and can be explained by the process of evaluative conditioning, in which an affective evaluative reaction evoked by an unconditional stimulus (US) is transferred to a conditional stimulus (CS). Much remains unknown about how disgust-related evaluative learning can be effectively eliminated. Study 1 of the present investigation examined the effects of extinction on reducing the negative evaluation of a CS that was acquired during disgust conditioning. Participants completed acquisition trials, with a disgusting picture as US and two neutral pictures as CS (CS+ was paired with the US; CS- was unpaired), followed by extinction trials ("CS only"; experimental condition) or a filler task (control condition). Extinction trials reduced acquired US expectancy to the CS+, but did not extinguish negative evaluations of the CS+. Study 2 examined the effects of counterconditioning on evaluative learned disgust. After disgust acquisition trials, counterconditioning trials followed in which the CS+ was paired with a pleasant US (experimental condition) or a filler task (control condition). Counterconditioning trials reduced acquired US expectancy to the CS+ and reduced evaluative conditioned disgust. Implications of the potential differential effects of extinction and counterconditioning on evaluative learning for exposure-based treatment of specific anxiety disorders are discussed. Copyright © 2014. Published by Elsevier Ltd.

Evidence for compliance with long-term medication: a systematic review of randomised controlled trials.

PubMed

King, Michelle A; Pryce, Rebecca L

2014-02-01

Pharmacists play a pivotal role in optimising medication use which often includes actions to maximise compliance with long-term medication. The best evidence to support medication use is derived from randomised controlled trials (RCTs). It is often assumed that 100 % compliance is required to obtain the outcomes identified in the trial. This assumption needs to be examined. To systematically review the reporting of compliance in RCTs of long-term medications. RCTs published in the New England Journal of Medicine, Journal of the American Medical Association, Lancet and BMJ in 2012, were reviewed to identify trials of medications for long-term use in adults. These trials were examined to evaluate the reporting of compliance. The proportion of trials reporting compliance data, the methods used, and the proportion of trials using more than one method to determine compliance. Of the 289 RCTs published in 2012, 25 assessed long-term medications in adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies used more than one method to measure compliance. Pill count was the most commonly reported method for measuring compliance, with patient reports and blood levels also being used. The reporting of compliance in RCTs is poor and the methodology inconsistent. The methods used overestimate compliance. If compliance in a clinical trial is low, the evidence for the effectiveness and most importantly safety of the medication(s) is questionable. Two or more methods, one of which is standardised, should be used to measure compliance in clinical trials. The requirement to report compliance should be included in publication guidelines.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.

PubMed

Abraha, Iosief; Cherubini, Antonio; Cozzolino, Francesco; De Florio, Rita; Luchetta, Maria Laura; Rimland, Joseph M; Folletti, Ilenia; Marchesi, Mauro; Germani, Antonella; Orso, Massimiliano; Eusebi, Paolo; Montedori, Alessandro

2015-05-27

To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Meta-epidemiological study. Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories). 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57). Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations. © Abraha et al 2015.

Systematic Review of Hydrotherapy Research: Does a Warm Bath in Labor Promote Normal Physiologic Childbirth?

PubMed

Shaw-Battista, Jenna

Health sciences research was systematically reviewed to assess randomized controlled trials of standard care versus immersion hydrotherapy in labor before conventional childbirth. Seven studies of 2615 women were included. Six trials examined hydrotherapy in midwifery care and found an effect of pain relief; of these, 2 examined analgesia and found reduced use among women who bathed in labor. One study each found that hydrotherapy reduced maternal anxiety and fetal malpresentation, increased maternal satisfaction with movement and privacy, and resulted in cervical dilation progress equivalent to standard labor augmentation practices. Studies examined more than 30 fetal and neonatal outcomes, and no benefit or harm of hydrotherapy was identified. Two trials had anomalous findings of increased newborn resuscitation or nursery admission after hydrotherapy, which were not supported by additional results in the same or other studies. Review findings demonstrate that intrapartum immersion hydrotherapy is a helpful and benign practice. Hydrotherapy facilitates physiologic childbirth and may increase satisfaction with care. Maternity care providers are recommended to include hydrotherapy among routine labor pain management options and consider immersion to promote progress of normal or protracted labor, particularly among women with preferences to avoid obstetric medications and procedures.

A Meta-analytic Review of Non-specific Effects in Randomized Controlled Trials of Cognitive Remediation for Schizophrenia.

PubMed

Radhakrishnan, Rajiv; Kiluk, Brian D; Tsai, Jack

2016-03-01

Cognitive remediation (CR) has been found to improve cognitive performance among adults with schizophrenia in randomized controlled trials (RCTs). However, improvements in cognitive performance are often observed in the control groups of RCTs as well. There has been no comprehensive examination of change in control groups for CR, which may inform trial methodology and improve our understanding of measured outcomes for cognitive remediation. In this meta-analysis, we calculated pre-post change in cognitive test performance within control groups of RCTs in 32 CR trials (n = 794 participants) published between 1970 and 2011, and examined the association between pre-post change and sample size, duration of treatment, type of control group, and participants' age, intelligence, duration of illness, and psychiatric symptoms. Results showed that control groups in CR trials showed small effect size changes (Cohen's d = 0.12 ± 0.16) in cognitive test performance over the trial duration. Study characteristics associated with pre-post change included participant age and sample size. These findings suggest attention to change in control groups may help improve detection of cognitive remediation effects for schizophrenia.

Interventions for increasing fruit and vegetable consumption in children aged five years and under.

PubMed

Hodder, Rebecca K; O'Brien, Kate M; Stacey, Fiona G; Wyse, Rebecca J; Clinton-McHarg, Tara; Tzelepis, Flora; James, Erica L; Bartlem, Kate M; Nathan, Nicole K; Sutherland, Rachel; Robson, Emma; Yoong, Sze Lin; Wolfenden, Luke

2018-05-17

Insufficient consumption of fruits and vegetables in childhood increases the risk of future non-communicable diseases, including cardiovascular disease. Interventions to increase consumption of fruit and vegetables, such as those focused on specific child-feeding strategies and parent nutrition education interventions in early childhood may therefore be an effective strategy in reducing this disease burden. To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. We searched CENTRAL, MEDLINE, Embase and two clinical trials registries to identify eligible trials on 25 January 2018. We searched Proquest Dissertations and Theses in November 2017. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included studies to identify further potentially relevant trials. We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. Two review authors independently extracted data and assessed the risks of bias of included studies; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures. We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. We included 63 trials with 178 trial arms and 11,698 participants. Thirty-nine trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Fourteen trials examined the impact of parent nutrition education in increasing child fruit and vegetable intake. Nine studies examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. One study examined the effect of a nutrition education intervention delivered to children in increasing child fruit and vegetable intake.We judged 14 of the 63 included trials as free from high risks of bias across all domains; performance, detection and attrition bias were the most common domains judged at high risk of bias for the remaining studies.There is very low quality evidence that child-feeding practices versus no intervention may have a small positive effect on child vegetable consumption equivalent to an increase of 3.50 g as-desired consumption of vegetables (SMD 0.33, 95% CI 0.13 to 0.54; participants = 1741; studies = 13). Multicomponent interventions versus no intervention may have a very small effect on child consumption of fruit and vegetables (SMD 0.35, 95% CI 0.04 to 0.66; participants = 2009; studies = 5; low-quality evidence), equivalent to an increase of 0.37 cups of fruit and vegetables per day. It is uncertain whether there are any short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.12, 95% CI -0.03 to 0.28; participants = 3078; studies = 11; very low-quality evidence).Insufficient data were available to assess long-term effectiveness, cost effectiveness and unintended adverse consequences of interventions. Studies reported receiving governmental or charitable funds, except for four studies reporting industry funding. Despite identifying 63 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains limited. There was very low- and low-quality evidence respectively that child-feeding practice and multicomponent interventions may lead to very small increases in fruit and vegetable consumption in children aged five years and younger. It is uncertain whether parent nutrition education interventions are effective in increasing fruit and vegetable consumption in children aged five years and younger. Given that the quality of the evidence is very low or low, future research will likely change estimates and conclusions. Long-term follow-up is required and future research should adopt more rigorous methods to advance the field.This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Effects of the Caregiver Interaction Profile Training on Caregiver-Child Interactions in Dutch Child Care Centers: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Helmerhorst, Katrien O.; Riksen-Walraven, J. Marianne; Fukkink, Ruben G.; Tavecchio, Louis W. C.; Gevers Deynoot-Schaub, Mirjam J. J. M.

2017-01-01

Background: Previous studies underscore the need to improve caregiver-child interactions in early child care centers. Objective: In this study we used a randomized controlled trial to examine whether a 5-week video feedback training can improve six key interactive skills of caregivers in early child care centers: Sensitive responsiveness, respect…

Examining the Test Of Memory Malingering Trial 1 and Word Memory Test Immediate Recognition as screening tools for insufficient effort.

PubMed

Bauer, Lyndsey; O'Bryant, Sid E; Lynch, Julie K; McCaffrey, Robert J; Fisher, Jerid M

2007-09-01

Assessing effort level during neuropsychological evaluations is critical to support the accuracy of cognitive test scores. Many instruments are designed to measure effort, yet they are not routinely administered in neuropsychological assessments. The Test of Memory Malingering (TOMM) and the Word Memory Test (WMT) are commonly administered symptom validity tests with sound psychometric properties. This study examines the use of the TOMM Trial 1 and the WMT Immediate Recognition (IR) trial scores as brief screening tools for insufficient effort through an archival analysis of a combined sample of mild head-injury litigants ( N = 105) who were assessed in forensic private practices. Results show that both demonstrate impressive diagnostic accuracy and calculations of positive and negative predictive power are presented for a range of base rates. These results support the utility of Trial 1 of the TOMM and the WMT IR trial as screening methods for the assessment of insufficient effort in neuropsychological assessments.

Incorporating multiple secondary targets into learning trials for individuals with autism spectrum disorder.

PubMed

Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany; Kisamore, April N

2017-07-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary target was presented in the consequence of each trial, and (d) no additional targets were presented trials. The participants acquired the majority of secondary targets. Presenting one or multiple secondary targets per trial, regardless of the location of these secondary targets, increased the efficiency of instruction in comparison to a condition with no secondary target. © 2017 Society for the Experimental Analysis of Behavior.

Performance determinants of fixed gear cycling during criteriums.

PubMed

Babault, Nicolas; Poisson, Maxime; Cimadoro, Guiseppe; Cometti, Carole; Païzis, Christos

2018-06-17

Nowadays, fixed gear competitions on outdoor circuits such as criteriums are regularly organized worldwide. To date, no study has investigated this alternative form of cycling. The purpose of the present study was to examine fixed gear performance indexes and to characterize physiological determinants of fixed gear cyclists. This study was carried out in two parts. Part 1 (n = 36) examined correlations between performance indexes obtained during a real fixed gear criterium (time trial, fastest laps, averaged lap time during races, fatigue indexes) and during a sprint track time trial. Part 2 (n = 9) examined correlations between the recorded performance indexes and some aerobic and anaerobic performance outputs (VO 2max , maximal aerobic power, knee extensor and knee flexor maximal voluntary torque, vertical jump height and performance during a modified Wingate test). Results from Part 1 indicated significant correlations between fixed gear final performance (i.e. average lap time during the finals) and single lap time (time trial, fastest lap during races and sprint track time trial). In addition, results from Part 2 revealed significant correlations between fixed gear performance and aerobic indicators (VO 2max and maximal aerobic power). However, no significant relationship was obtained between fixed gear cycling and anaerobic qualities such as strength. Similarly to traditional cycling disciplines, we concluded that fixed gear cycling is mainly limited by aerobic capacity, particularly criteriums final performance. However, specific skills including technical competency should be considered.

A comparison of speech and language therapy techniques for dysarthria in Parkinson's disease.

PubMed

Deane, K H; Whurr, R; Playford, E D; Ben-Shlomo, Y; Clarke, C E

2001-01-01

Dysarthria is a common manifestation of Parkinson's disease that increases in frequency and intensity with the progress of the disease (Streifler 1984). Up to 20% of Parkinsonian patients are referred for speech and language therapy (S & LT), its aim being to improve the intelligibility of the patient's speech. To compare the efficacy and effectiveness of novel S & LT techniques versus standard S & LT to treat dysarthria in patients with Parkinson's disease. To compare the efficacy and effectiveness of one S & LT technique versus a second form of S & LT to treat Parkinsonian dysarthria. Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, ISI-SCI, AMED, MANTIS, REHABDATA, REHADAT, GEROLIT, Pascal, LILACS, MedCarib, JICST-EPlus, AIM, IMEMR, SIGLE, ISI-ISTP, DISSABS, Conference Papers Index, Aslib Index to Theses, the Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, CRISP, PEDro, NIDRR and NRR; and examination of the reference lists of identified studies and other reviews. Only randomised controlled trials (RCT) were included. Data was abstracted independently by KD and RW and differences settled by discussion. Only two trials were identified with only 71 patients. The method of randomisation was good in only one trial and the concealment of allocation was inadequate in both trials. These methodological problems could potentially lead to bias from a number of sources. The methods used in the two studies varied so much that meta-analysis of the results was not possible. Scott 83 compared prosodic exercises with visual cues with prosodic exercises alone (See Glossary: Table 01). The authors examined prosody and intelligibility as outcome measures immediately after therapy. Ramig 95 compared the Lee Silverman Voice Therapy (LSVT) which emphasises increased vocal effort, with respiratory therapy which aimed to increase respiratory muscle activity. Ramig 95 examined a wide range of vocal characteristics, activities of daily living affected by speech, depression and the carer's impressions of the patient's speech quality. Some of these outcomes were measured up to 24 months after the end of the therapy. However, in neither study were changes in outcomes due to 'Therapy A' compared with the changes due to 'Therapy B' statistically. Therefore no comment on the comparative efficacy of these types of speech and language therapy can be made. Considering the methodological flaws in both of these studies, the small number of patients examined, and the possibility of publication bias, there is insufficient evidence to support or refute the efficacy of any given form of S & LT over another to treat dysarthria in Parkinson's disease. Given the lack of evidence from RCTs to support or refute the efficacy of S & LT in Parkinson's disease (see Cochrane review 'Speech and Language therapy for Dysarthria in Patients with Parkinson's Disease'), the consensus as to what is considered 'best-practice' S & LT must be proved first through a large well-designed placebo-controlled randomised trial before examining variations in S & LT methodology. The design of these trials should minimise bias and be reported fully using CONSORT guidelines (CONSORT 1996). Outcome measures with particular relevance to patients, their carers, physicians and speech and language therapists should be chosen and the patients followed for at least 6 months to determine the duration of any improvement.

Brief Alcohol Intervention Trials Conducted by Higher Prestige Authors and Published in Higher Impact Factor Journals are Cited More Frequently

PubMed Central

Tanner-Smith, Emily E.; Polanin, Joshua R.

2016-01-01

Objective To examine the relationships between study quality, author prestige, journal impact factors, and citation rates of trials; and to examine whether journal impact factors mediated the relationships between study quality and author prestige on citation rates. Study Design and Setting We used bibliometric data from 128 controlled trials included in a recent meta-analysis on brief alcohol interventions (BAIs) for adolescents and young adults. We obtained the number of citations from ISI Web of Knowledge and Google Scholar; journal impact factors were obtained from ISI Web of Knowledge. Linear regression models were used to examine the direct and indirect effects of interest. Results The results indicated that studies were published in journals with higher impact factors when first authors had higher h-indices and studies were funded, but this was largely because those studies were of higher quality. Studies were cited more frequently when first authors had higher h-indices and studies were funded, even after adjusting for study quality proxies. The observed associations between study quality and author prestige on citation rates were also partly mediated through journal impact factors. Conclusion We conclude that studies conducted by more established authors and reported in more prestigious journal outlets are more likely to be cited by other scholars, even after controlling for various proxies of study quality. PMID:26854420

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far?

PubMed Central

Keefe, Richard S. E.; Buchanan, Robert W.; Marder, Stephen R.; Schooler, Nina R.; Dugar, Ashish; Zivkov, Milana; Stewart, Michelle

2013-01-01

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website “www.clinicaltrials.gov” using the terms “schizophrenia AND cognition,” “schizophrenia AND neurocognition,” “schizophrenia AND neurocognitive tests,” “schizophrenia AND MATRICS,” “schizophrenia AND MCCB,” “schizophrenia AND BACS,” “schizophrenia AND COGSTATE,” and “schizophrenia AND CANTAB” and “first-episode schizophrenia AND cognition.” The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia. PMID:22114098

Last resort or roll of the die? Exploring the role of metaphors in cancer clinical trials education among medically underserved populations.

PubMed

Krieger, Janice L

2014-01-01

Improving communication about cancer clinical trials may help increase patients' understanding of medical research and their interest in participating. It is unfortunate that there is little empirical research to provide guidance on how to adapt clinical trial messages to maximize cultural sensitivity. This study examines (a) how medically underserved women conceptualize clinical trials by examining the language they use to describe them and (b) how this audience interprets metaphorical language used to explain randomization in the context of Phase III cancer clinical trials. The author conducted in-depth interviews and focus groups with 41 rural, low-income older women who either had been diagnosed with cancer or were caregivers for a person with cancer. The most commonly used lay metaphors for clinical trials had strong negative connotations and included treatment by trial and error, patients are guinea pigs, and treatment of last resort. Participants also expressed strong, unfavorable responses to conventional metaphors that equate randomization with the roll of a die or use other gambling language. Low-literacy definition approaches were unexpectedly problematic, suggesting the potential effectiveness of culturally grounded metaphors for communicating about clinical trials. Ethical implications of these findings for cancer communication are discussed.

Brief alcohol intervention trials conducted by higher prestige authors and published in higher impact factor journals are cited more frequently.

PubMed

Tanner-Smith, Emily E; Polanin, Joshua R

2016-07-01

To examine the relationships between study quality, author prestige, journal impact factors, and citation rates of trials and to examine whether journal impact factors mediated the relationships between study quality and author prestige on citation rates. We used bibliometric data from 128 controlled trials included in a recent meta-analysis on brief alcohol interventions for adolescents and young adults. We obtained the number of citations from ISI Web of Knowledge and Google Scholar; journal impact factors were obtained from ISI Web of Knowledge. Linear regression models were used to examine the direct and indirect effects of interest. The results indicated that studies were published in journals with higher impact factors when first authors had higher h-indices and studies were funded, but this was largely because those studies were of higher quality. Studies were cited more frequently when first authors had higher h-indices and studies were funded, even after adjusting for study quality proxies. The observed associations between study quality and author prestige on citation rates were also partly mediated through journal impact factors. We conclude that studies conducted by more established authors and reported in more prestigious journal outlets are more likely to be cited by other scholars, even after controlling for various proxies of study quality. Copyright © 2016 Elsevier Inc. All rights reserved.

Anal Cancer: An Examination of Radiotherapy Strategies

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

Glynne-Jones, Rob; Lim, Faye

2011-04-01

The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are nomore » meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.« less

Chocolate scents and product sales: a randomized controlled trial in a Canadian bookstore and café.

PubMed

McGrath, Mary C; Aronow, Peter M; Shotwell, Vivien

2016-01-01

We report the results of a 31-day trial on the effects of chocolate scent on purchasing behavior in a bookstore. Our study replicates and extends a 10-day randomized controlled trial in order to examine the generalizability of the original finding. We first introduce the study of store atmospherics and highlight the importance and dearth of replication in this area. In the next section, we describe the original study and discuss the theory of ambient scent effects on product sales, and the role of scent-product congruity. We then describe our design and methods, followed by presentation and discussion of our results. We find no evidence that chocolate scent affects sales. These findings indicate the importance of replication in varied settings. Contextual factors and the choices available to customers may moderate the effects of ambient scent on purchasing behavior. Our study highlights the value of examining the generalizability of experimental findings, both for theory and practice.

Criminal defense in Chinese courtrooms: an empirical inquiry.

PubMed

Liang, Bin; He, Ni Phil

2014-10-01

Scholars in the field of Chinese criminal procedure law study have long decried the meager legal protection afforded to criminal defendants on trial and the hapless status of Chinese criminal defense attorneys in the courtroom. Unfortunately, very little empirical evidence was available to shed light on how criminal defense was carried out in Chinese courtrooms. Based on observations of 325 actual criminal trials from 55 District People's Courts in J province, this study provides an opportunity to understand the mundane work performed by Chinese criminal defense attorneys. In particular, this study describes how criminal defense attorneys prepare and present their cases (as measured in terms of bail request, overall trial preparation, examination of defendants and witnesses, presentation of evidence, and overall defense strategy), and analyzes the outcomes of their performance. In addition, this study examines the discernible impact of criminal defense work due to types of legal representation utilized (legal aid vs. privately retained attorneys), numbers of attorneys representing the client, and the gender composition of the attorneys. © The Author(s) 2013.

A Systematic Review of Surgical Randomized Controlled Trials: Part 2. Funding Source, Conflict of Interest, and Sample Size in Plastic Surgery.

PubMed

Voineskos, Sophocles H; Coroneos, Christopher J; Ziolkowski, Natalia I; Kaur, Manraj N; Banfield, Laura; Meade, Maureen O; Chung, Kevin C; Thoma, Achilleas; Bhandari, Mohit

2016-02-01

The authors examined industry support, conflict of interest, and sample size in plastic surgery randomized controlled trials that compared surgical interventions. They hypothesized that industry-funded trials demonstrate statistically significant outcomes more often, and randomized controlled trials with small sample sizes report statistically significant results more frequently. An electronic search identified randomized controlled trials published between 2000 and 2013. Independent reviewers assessed manuscripts and performed data extraction. Funding source, conflict of interest, primary outcome direction, and sample size were examined. Chi-squared and independent-samples t tests were used in the analysis. The search identified 173 randomized controlled trials, of which 100 (58 percent) did not acknowledge funding status. A relationship between funding source and trial outcome direction was not observed. Both funding status and conflict of interest reporting improved over time. Only 24 percent (six of 25) of industry-funded randomized controlled trials reported authors to have independent control of data and manuscript contents. The mean number of patients randomized was 73 per trial (median, 43, minimum, 3, maximum, 936). Small trials were not found to be positive more often than large trials (p = 0.87). Randomized controlled trials with small sample size were common; however, this provides great opportunity for the field to engage in further collaboration and produce larger, more definitive trials. Reporting of trial funding and conflict of interest is historically poor, but it greatly improved over the study period. Underreporting at author and journal levels remains a limitation when assessing the relationship between funding source and trial outcomes. Improved reporting and manuscript control should be goals that both authors and journals can actively achieve.

Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

PubMed

Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

2012-01-03

To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

Selectivity of N170 for visual words in the right hemisphere: Evidence from single-trial analysis.

PubMed

Yang, Hang; Zhao, Jing; Gaspar, Carl M; Chen, Wei; Tan, Yufei; Weng, Xuchu

2017-08-01

Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single-trial analysis. Results show that words evoked greater single-trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial-to-trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial-to-trial peak latency for responses to words over the right hemisphere. © 2017 Society for Psychophysiological Research.

Robotic technology results in faster and more robust surgical skill acquisition than traditional laparoscopy.

PubMed

Moore, Lee J; Wilson, Mark R; Waine, Elizabeth; Masters, Rich S W; McGrath, John S; Vine, Samuel J

2015-03-01

Technical surgical skills are said to be acquired quicker on a robotic rather than laparoscopic platform. However, research examining this proposition is scarce. Thus, this study aimed to compare the performance and learning curves of novices acquiring skills using a robotic or laparoscopic system, and to examine if any learning advantages were maintained over time and transferred to more difficult and stressful tasks. Forty novice participants were randomly assigned to either a robotic- or laparoscopic-trained group. Following one baseline trial on a ball pick-and-drop task, participants performed 50 learning trials. Participants then completed an immediate retention trial and a transfer trial on a two-instrument rope-threading task. One month later, participants performed a delayed retention trial and a stressful multi-tasking trial. The results revealed that the robotic-trained group completed the ball pick-and-drop task more quickly and accurately than the laparoscopic-trained group across baseline, immediate retention, and delayed retention trials. Furthermore, the robotic-trained group displayed a shorter learning curve for accuracy. The robotic-trained group also performed the more complex rope-threading and stressful multi-tasking transfer trials better. Finally, in the multi-tasking trial, the robotic-trained group made fewer tone counting errors. The results highlight the benefits of using robotic technology for the acquisition of technical surgical skills.

Changing case Order to Optimise patterns of Performance in mammography Screening (CO-OPS): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background X-ray mammography remains the predominant test for screening for breast cancer, with the aim of reducing breast cancer mortality. In the English NHS Breast Screening Programme each woman’s mammograms are examined separately by two expert readers. The two readers read each batch in the same order and each indicates if there should be recall for further tests. This is a highly skilled, pressurised, repetitive and frequently intellectually unchallenging activity where readers examine one or more batches of 30–50 women’s mammograms in each session. A vigilance decrement or performance decrease over time has been observed in similar repetitive visual tasks such as radar operation. Methods/Design The CO-OPS study is a pragmatic, multi-centre, two-arm, double blind cluster randomised controlled trial of a computer software intervention designed to reduce the effects of a vigilance decrement in breast cancer screening. The unit of randomisation is the batch. Intervention batches will be examined in the opposite order by the two readers (one forwards, one backwards). Control batches will be read in the same order as one another, as is current standard practice. The hypothesis is that cancer detection rates will be higher in the intervention group because each readers’ peak performance will occur when examining different women’s mammograms. The trial will take place in 44 English breast screening centres for 1 year and 4 months. The primary outcome is cancer detection rate, which will be extracted from computer records after 1 year of the trial. The secondary outcomes include rate of disagreement between readers (a more statistically powerful surrogate for cancer detection rate), recall rate, positive predictive value, and interval cancer rate (cancers found between screening rounds which will be measured three years after the end of the trial). Discussion This is the first trial of an intervention to ameliorate a vigilance decrement in breast cancer screening. Trial registration ISRCTN46603370 (submitted: 24 October 2012, date of registration: 26 March 2013). PMID:24411004

Clinical trials of artesunate plus sulfadoxine-pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction.

PubMed

Awab, Ghulam Rahim; Imwong, Mallika; Pukrittayakamee, Sasithon; Alim, Fazel; Hanpithakpong, Warunee; Tarning, Joel; Dondorp, Arjen M; Day, Nicholas P J; White, Nicholas J; Woodrow, Charles J

2016-02-25

Combination therapy with artesunate plus sulfadoxine-pyrimethamine (SP) was adopted as recommended treatment for Plasmodium falciparum infection in Afghanistan in 2003. A series of prospective clinical studies examining the efficacy of artesunate plus sulfadoxine-pyrimethamine (AS + SP) against P. falciparum were undertaken in sentinel sites in Afghanistan from 2007 to 2014, accompanied by relevant molecular studies. The first study was a randomized trial of AS + SP versus dihydroartemisinin-piperaquine, while two subsequent studies were standard therapeutic efficacy studies of AS + SP. Three hundred and three patients were enrolled across four provinces in the north and east of the country. Curative efficacy was high in all the trials, with an adequate clinical and parasitological response (ACPR) of more than 95 % in all groups and trial stages. Genotyping for drug-resistance alleles at dhfr indicated fixation of the S108 N mutation and a prevalence of the C59R mutation of approximately 95 % across all sites. Other mutations in dhfr and dhps remained rare or absent entirely, although five isolates from the first trial carried the dhps triple mutant SGEGA haplotype. In the last study undertaken in 2012-2014 the K13 artemisinin resistance marker was examined; only two of 60 successfully sequenced samples carried a K13-propeller mutation. These data confirm maintained efficacy 10 years after introduction of artesunate plus SP as combination treatment of P. falciparum in Afghanistan. The molecular data indicate that despite a substantial fall in incidence, resistance has not developed to artemisinins, or intensified to the ACT partner drug components. Trial Registration http://www.clinicaltrials.gov/ct NCT00682578, NCT01115439 and NCT01707199.

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Ethical issues in a stage 1 cognitive-behavioral therapy feasibility study and trial to reduce alcohol use among HIV-infected outpatients in western Kenya.

PubMed

Papas, Rebecca K; Gakinya, Benson N; Baliddawa, Joyce B; Martino, Steve; Bryant, Kendall J; Meslin, Eric M; Sidle, John E

2012-07-01

Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them.

Ethical Issues in a Stage 1 Cognitive-Behavioral Therapy Feasibility Study and Trial to Reduce Alcohol Use Among HIV-Infected Outpatients in Western Kenya

PubMed Central

Papas, Rebecca K.; Gakinya, Benson N.; Baliddawa, Joyce B.; Martino, Steve; Bryant, Kendall J.; Meslin, Eric M.; Sidle, John E.

2013-01-01

Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them. PMID:22850141

WWC Review of the Report "Interactive Learning Online at Public Universities: Evidence from a Six-Campus Randomized Trial." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

The 2013 study, "Interactive Learning Online at Public Universities: Evidence From a Six-Campus Randomized Trial," examined the impact of interactive learning online (ILO) on the pass rates of 605 students enrolled in introductory statistics courses at six public universities. ILO is a form of online course instruction in which…

Compliance with results reporting at ClinicalTrials.gov.

PubMed

Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M

2015-03-12

The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).

Tai Chi exercise in improving cardiorespiratory capacity.

PubMed

Thornton, Everard W

2008-01-01

To evaluate evidence relating to effects of Tai Chi on cardiovascular outcomes, with emphasis on randomised control designs. Studies reviewed in 2004 were re-examined, together with more recent controlled trials of Tai Chi relating to cardiovascular outcome. The analysis provided comment on problems associated with randomised control design, including sources of bias in such trials. With a single exception, data support reduction of baseline systolic/diastolic blood pressure (BP). While there may be positive bias in these studies, data are from diverse ethnic groups, different gender, age, and level of functional ability. There are no data relating to BP reactive change to subsequent stressors. Few studies consider potential mediating mechanisms through which Tai Chi may provide these benefits. Caution is advocated in using randomised controlled trials as the only effective type of study. Such designs are difficult to conduct and effective trials are more likely given a better understanding of the mediating mechanism(s) through which benefits may be derived. It is currently unclear how changes in BP are derived. Some data indicate a shift to increased vagal relative to sympathetic dominance and there may be other potential physiological mediators. No study has examined relationships between potential psychological gains such as self-efficacy and BP change, or individual differences in outcomes.

‘Trial Exegesis’: Methods for Synthesizing Clinical and Patient Reported Outcome (PRO) Data in Trials to Inform Clinical Practice. A Systematic Review

PubMed Central

Macefield, Rhiannon C.; Blencowe, Natalie S.; Brookes, Sara T.; Blazeby, Jane M.

2016-01-01

Purpose The CONSORT extension for patient reported outcomes (PROs) aims to improve reporting, but guidance on the optimal integration with clinical data is lacking. This study examines in detail the reporting of PROs and clinical data from randomized controlled trials (RCTs) in gastro-intestinal cancer to inform design and reporting of combined PRO and clinical data from trials to improve the ‘take home’ message for clinicians to use in practice. Materials and Methods The case study was undertaken in gastro-intestinal cancer trials. Well-conducted RCTs reporting PROs with validated instruments were identified and categorized into those combining PRO and clinical data in a single paper, or those separating data into linked primary and supplemental papers. Qualitative methods were developed to examine reporting of the critical interpretation of the trial results (trial exegesis) in the papers in relation of the PRO and clinical outcomes and applied to each publication category. Results were used to inform recommendations for practice. Results From 1917 screened abstracts, 49 high quality RCTs were identified reported in 36 combined and 15 linked primary and supplemental papers. In-depth analysis of manuscript text identified three categories for understanding trial exegesis: where authors reported a “detailed”, “general”, or absent PRO rationale and integrated interpretation of clinical and PRO results. A total of 11 (30%) and 6 (16%) combined papers reported “detailed” PRO rationale and integrated interpretation of results although only 2 (14%) and 1 (7%) primary papers achieved the same standard respectively. Supplemental papers provide better information with 11 (73%) and 3 (20%) achieving “detailed” rationale and integrated interpretation of results. Supplemental papers, however, were published a median of 20 months after the primary RCT data in lower impact factor journals (median 16.8 versus 5.2). Conclusion It is recommended that single papers, with detailed PRO rationale and integrated PRO and clinical data are published to optimize trial exegesis. Further work to examine whether this improves the use of PRO data to inform practice is needed. PMID:27571514

Adolescent decision making about participation in a hypothetical HIV vaccine trial.

PubMed

Alexander, Andreia B; Ott, Mary A; Lally, Michelle A; Sniecinski, Kevin; Baker, Alyne; Zimet, Gregory D

2015-03-10

The purpose of this study was to examine the process of adolescent decision-making about participation in an HIV vaccine clinical trial, comparing it to adult models of informed consent with attention to developmental differences. As part of a larger study of preventive misconception in adolescent HIV vaccine trials, we interviewed 33 male and female 16-19-year-olds who have sex with men. Participants underwent a simulated HIV vaccine trial consent process, and then completed a semistructured interview about their decision making process when deciding whether or not to enroll in and HIV vaccine trial. An ethnographic content analysis approach was utilized. Twelve concepts related to adolescents' decision-making about participation in an HIV vaccine trial were identified and mapped onto Appelbaum and Grisso's four components of decision making capacity including understanding of vaccines and how they work, the purpose of the study, trial procedures, and perceived trial risks and benefits, an appreciation of their own situation, the discussion and weighing of risks and benefits, discussing the need to consult with others about participation, motivations for participation, and their choice to participate. The results of this study suggest that most adolescents at high risk for HIV demonstrate the key abilities needed to make meaningful decisions about HIV vaccine clinical trial participation. Published by Elsevier Ltd.

Developmental Effects of Incentives on Response Inhibition

PubMed Central

Geier, Charles F.; Luna, Beatriz

2012-01-01

Inhibitory control and incentive processes underlie decision-making, yet few studies have explicitly examined their interaction across development. Here, the effects of potential rewards and losses on inhibitory control in sixty-four adolescents (13-17-year-olds) and forty-two young adults (18-29-year-olds) were examined using an incentivized antisaccade task. Notably, measures were implemented to minimize age-related differences in reward valuation and potentially confounding motivation effects. Incentives affected antisaccade metrics differently across the age groups. Younger adolescents generated more errors than adults on reward trials, but all groups performed well on loss trials. Adolescent saccade latencies also differed from adults across the range of reward trials. Overall, results suggest persistent immaturities in the integration of reward and inhibitory control processes across adolescence. PMID:22540668

A randomized controlled trial on errorless learning in goal management training: study rationale and protocol

PubMed Central

2013-01-01

Background Many brain-injured patients referred for outpatient rehabilitation have executive deficits, notably difficulties with planning, problem-solving and goal directed behaviour. Goal Management Training (GMT) has proven to be an efficacious cognitive treatment for these problems. GMT entails learning and applying an algorithm, in which daily tasks are subdivided into multiple steps. Main aim of the present study is to examine whether using an errorless learning approach (preventing the occurrence of errors during the acquisition phase of learning) contributes to the efficacy of Goal Management Training in the performance of complex daily tasks. Methods/Design The study is a double blind randomized controlled trial, in which the efficacy of Goal Management Training with an errorless learning approach will be compared with conventional Goal Management Training, based on trial and error learning. In both conditions 32 patients with acquired brain injury of mixed etiology will be examined. Main outcome measure will be the performance on two individually chosen everyday-tasks before and after treatment, using a standardized observation scale and goal attainment scaling. Discussion This is the first study that introduces errorless learning in Goal Management Training. It is expected that the GMT-errorless learning approach will improve the execution of complex daily tasks in brain-injured patients with executive deficits. The study can contribute to a better treatment of executive deficits in cognitive rehabilitation. Trial registration (Dutch Trial Register): http://NTR3567 PMID:23786651

Effects of whole body vibration on pulmonary function, functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease: a systematic review.

PubMed

Yang, Xiaotian; Zhou, Yujing; Wang, Pu; He, Chengqi; He, Hongchen

2016-05-01

To examine the effect of whole-body vibration in enhancing pulmonary function, functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease and examine its safety. Randomized controlled trials examining the effects of whole body vibration among people with chronic obstructive pulmonary disease were identified by two independent researchers. Articles were excluded if they were studies on people with other primary diagnosis, abstracts published in the conferences or books. PEDro scale was used to assess the methodological quality of the selected studies. We evaluated the level of evidence by using the GRADE approach. The results were extracted by two researchers and confirmed by the third researcher if disagreement existed. Sources included Cochrane Central Register of Controlled Trials, PubMed, CINAHL, EMBASE, PEDro, AMED, PsycINFO, ClinicalTrials.gov, Current Controlled Trials and reference lists of all relevant articles. Four studies involving 206 participants were included in this systematic review. Methodological quality was rated as good for two studies. No great benefits on pulmonary function were found in whole body vibration treatment group. Two studies showed that quality of life was improved in people with chronic obstructive pulmonary disease. Whole body vibration led to significant improvements in functional exercise capacity measured with six minutes walking test. Nearly no adverse events were observed. Whole body vibration may improve functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease. There was insufficient evidence to prove the effects of whole body vibration on pulmonary function. © The Author(s) 2015.

Reappraising the phototoxicity of tretinoin: a report of four controlled clinical trials.

PubMed

Slade, Herbert B; Shroot, Braham; Feldman, Steven R; Cargill, D Innes; Stanfield, Joe

2009-06-01

Retinoids are photoreactive molecules found in skin and retinal tissue. The use of retinoids in pharmacologic doses, applied topically, raises the potential of phototoxicities. Recent review articles and current US drug labeling indicate that tretinoin is a phototoxin. In developing a new formulation of topical all-trans-retinoic acid (tretinoin), formal testing of dermal photoreactions was therefore undertaken. Four prospective, randomized, and controlled trials were carried out in healthy volunteers at two independent research facilities. Two trials examined phototoxicity following 24 h of drug exposure under occlusion (combined n=51), and two examined photoallergenicity following a 3-week, six dose induction phase (combined n=72) followed by challenge. No phototoxic or photoallergic reactions occurred with tretinoin 0.05% in a new gel formulation. The findings in these studies are consistent with previous studies of tretinoin in various formulations, and support the conclusion that tretinoin appears to be neither phototoxic nor photoallergenic in vivo.

Psychosocial interventions to improve quality of life and emotional wellbeing for recently diagnosed cancer patients.

PubMed

Galway, Karen; Black, Amanda; Cantwell, Marie; Cardwell, Chris R; Mills, Moyra; Donnelly, Michael

2012-11-14

A cancer diagnosis may lead to significant psychological distress in up to 75% of cases. There is a lack of clarity about the most effective ways to address this psychological distress. To assess the effects of psychosocial interventions to improve quality of life (QoL) and general psychological distress in the 12-month phase following an initial cancer diagnosis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE, EMBASE, and PsycINFO up to January 2011. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Electronic searches were carried out across all primary sources of peer-reviewed publications using detailed criteria. No language restrictions were imposed. Randomised controlled trials of psychosocial interventions involving interpersonal dialogue between a 'trained helper' and individual newly diagnosed cancer patients were selected. Only trials measuring QoL and general psychological distress were included. Trials involving a combination of pharmacological therapy and interpersonal dialogue were excluded, as were trials involving couples, family members or group formats. Trial data were examined and selected by two authors in pairs with mediation from a third author where required. Where possible, outcome data were extracted for combining in a meta-analyses. Continuous outcomes were compared using standardised mean differences and 95% confidence intervals, using a random-effects model. The primary outcome, QoL, was examined in subgroups by outcome measurement, cancer site, theoretical basis for intervention, mode of delivery and discipline of trained helper. The secondary outcome, general psychological distress (including anxiety and depression), was examined according to specified outcome measures. A total of 3309 records were identified, examined and the trials subjected to selection criteria; 30 trials were included in the review. No significant effects were observed for QoL at 6-month follow up (in 9 studies, SMD 0.11; 95% CI -0.00 to 0.22); however, a small improvement in QoL was observed when QoL was measured using cancer-specific measures (in 6 studies, SMD 0.16; 95% CI 0.02 to 0.30). General psychological distress as assessed by 'mood measures' improved also (in 8 studies, SMD - 0.81; 95% CI -1.44 to - 0.18), but no significant effect was observed when measures of depression or anxiety were used to assess distress (in 6 studies, depression SMD 0.12; 95% CI -0.07 to 0.31; in 4 studies, anxiety SMD 0.05; 95% CI -0.13 to 0.22). Psychoeducational and nurse-delivered interventions that were administered face to face and by telephone with breast cancer patients produced small positive significant effects on QoL (in 2 studies, SMD 0.23; 95% CI 0.04 to 0.43). The significant variation that was observed across participants, mode of delivery, discipline of 'trained helper' and intervention content makes it difficult to arrive at a firm conclusion regarding the effectiveness of psychosocial interventions for cancer patients. It can be tentatively concluded that nurse-delivered interventions comprising information combined with supportive attention may have a beneficial impact on mood in an undifferentiated population of newly diagnosed cancer patients.

Characteristics of clinical trial websites: information distribution between ClinicalTrials.gov and 13 primary registries in the WHO registry network.

PubMed

Ogino, Daisuke; Takahashi, Kunihiko; Sato, Hajime

2014-11-05

It is well known that information about clinical trials is not easily accessible by the public. In Japan, clinical trial information can be accessed by the general public through online registries; however, many people find these registries difficult to use. To improve current clinical trial registries, we propose that combining them with clinical information phrased in lay terms would be beneficial to other interested professionals such as journalists and clinicians, as well as the general public. Therefore, this study aimed to examine the current pattern of distribution of clinical trial information from the primary World Health Organization (WHO) registries. Based on the results of this assessment, we then aimed to build and evaluate a prototype of the Japan Primary Registries Network (JPRN) portal that would be easily accessible to patients and the public, while still remaining useful for professionals. We assessed a total of 14 primary clinical trial registries listed on the WHO International Clinical Trials Registry Platform between January and February 2013. Website content was accessed and checked against a series of items that looked at usability, communication, design and accessibility of the sites. We excluded registries that were not active or were not on the approved WHO registry list at the time of our assessment. We also examined only the English versions of the websites as native-language registries may offer more functionality or different content than the English version of the same website. All registries examined had a function allowing users to search the registry data and that displayed the related information from the search, including the clinical trial registration data. However, few websites were found to be user-friendly, and there was little integration with social media. We confirmed that there are few websites providing useful clinical trial information to patients and their families. However, information gleaned from some of the more advanced online registries could be used to improve the content and functionality of the JPRN portal.

Testing Unsuccessfully: A Specification of the Underlying Mechanisms Supporting Its Influence on Retention

ERIC Educational Resources Information Center

Knight, Justin B.; Ball, B. Hunter; Brewer, Gene A.; DeWitt, Michael R.; Marsh, Richard L.

2012-01-01

Five experiments were conducted to examine how unsuccessful retrieval influences learning and subsequent memory. We used a cued-recall paradigm that produces many unsuccessful retrieval attempts (followed by feedback) and allows comparisons to be made between later memory for these trials and trials that only required reading or studying the…

Speech Compensation for Time-Scale-Modified Auditory Feedback

ERIC Educational Resources Information Center

Ogane, Rintaro; Honda, Masaaki

2014-01-01

Purpose: The purpose of this study was to examine speech compensation in response to time-scale-modified auditory feedback during the transition of the semivowel for a target utterance of /ija/. Method: Each utterance session consisted of 10 control trials in the normal feedback condition followed by 20 perturbed trials in the modified auditory…

The Relations among Measurements of Informant Discrepancies within a Multisite Trial of Treatments for Childhood Social Phobia

ERIC Educational Resources Information Center

De Los Reyes, Andres; Alfano, Candice A.; Beidel, Deborah C.

2010-01-01

Discrepancies between informants' reports of children's behavior are robustly observed in clinical child research and have important implications for interpreting the outcomes of controlled treatment trials. However, little is known about the basic psychometric properties of these discrepancies. This study examined the relation between…

Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

ERIC Educational Resources Information Center

Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

2010-01-01

Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

Evaluation of Parent and Child Enhancement (PACE) Program: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Lo, Cyrus

2017-01-01

Objective: This study examined the efficacy of the Parent and Child Enhancement (PACE) program on child learning, child behavior problems, and parental stress, using randomized controlled trial design, in social services centers. Methods: Eligibility criteria were (1) children aged 2 years at program commencement, (2) low-income, new immigrant, or…

Virtual Learning Intervention to Reduce Bullying Victimization in Primary School: A Controlled Trial

ERIC Educational Resources Information Center

Sapouna, Maria; Wolke, Dieter; Vannini, Natalie; Watson, Scott; Woods, Sarah; Schneider, Wolfgang; Enz, Sibylle; Hall, Lynne; Paiva, Ana; Andre, Elizabeth; Dautenhahn, Kerstin; Aylett, Ruth

2010-01-01

Background: Anti-bullying interventions to date have shown limited success in reducing victimization and have rarely been evaluated using a controlled trial design. This study examined the effects of the FearNot! anti-bullying virtual learning intervention on escaping victimization, and reducing overall victimization rates among primary school…

Nodulation ability of the common bean genotypes composing the BASE 120 trial after inoculation with Rhizobium

USDA-ARS?s Scientific Manuscript database

This study examined the nodulation characteristics of the BASE 120 genotypes in a trial of 118 common bean (Phaseolus vulgaris L.) and two tepary bean (Phaseolus acutifolius) lines. Inoculation with Rhizobium tropici strain CIAT 899 and Rhizobium etli strain CIAT 632 was carried out in a screenhouse...

Theory-Driven Process Evaluation of a Complementary Feeding Trial in Four Countries

ERIC Educational Resources Information Center

Newman, Jamie E.; Garces, Ana; Mazariegos, Manolo; Hambidge, K. Michael; Manasyan, Albert; Tshefu, Antoinette; Lokangaka, Adrien; Sami, Neelofar; Carlo, Waldemar A.; Bose, Carl L.; Pasha, Omrana; Goco, Norman; Chomba, Elwyn; Goldenberg, Robert L.; Wright, Linda L.; Koso-Thomas, Marion; Krebs, Nancy F.

2014-01-01

We conducted a theory-driven process evaluation of a cluster randomized controlled trial comparing two types of complementary feeding (meat versus fortified cereal) on infant growth in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo. We examined process evaluation indicators for the entire study cohort (N = 1236) using chi-square…

Object-Based Control of Attention Is Sensitive to Recent Experience

ERIC Educational Resources Information Center

Lee, Hyunkyu; Mozer, Michael C.; Kramer, Arthur F.; Vecera, Shaun P.

2012-01-01

How is attention guided by past experience? In visual search, numerous studies have shown that recent trials influence responses to the current trial. Repeating features such as color, shape, or location of a target facilitates performance. Here we examine whether recent experience also modulates a more abstract dimension of attentional control,…

The Lifestyle Interventions and Independence for Elders (LIFE) study, randomized trial of physical activity: Effect on the prevention of major mobility disability

USDA-ARS?s Scientific Manuscript database

In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining if physical activi...

A Systematic Review of Community-Based Participatory Research to Enhance Clinical Trials in Racial and Ethnic Minority Groups

PubMed Central

De Las Nueces, Denise; Hacker, Karen; DiGirolamo, Ann; Hicks, LeRoi S

2012-01-01

Objective To examine the effectiveness of current community-based participatory research (CBPR) clinical trials involving racial and ethnic minorities. Data Source All published peer-reviewed CBPR intervention articles in PubMed and CINAHL databases from January 2003 to May 2010. Study Design We performed a systematic literature review. Data Collection/Extraction Methods Data were extracted on each study's characteristics, community involvement in research, subject recruitment and retention, and intervention effects. Principle Findings We found 19 articles meeting inclusion criteria. Of these, 14 were published from 2007 to 2010. Articles described some measures of community participation in research with great variability. Although CBPR trials examined a wide range of behavioral and clinical outcomes, such trials had very high success rates in recruiting and retaining minority participants and achieving significant intervention effects. Conclusions Significant publication gaps remain between CBPR and other interventional research methods. CBPR may be effective in increasing participation of racial and ethnic minority subjects in research and may be a powerful tool in testing the generalizability of effective interventions among these populations. CBPR holds promise as an approach that may contribute greatly to the study of health care delivery to disadvantaged populations. PMID:22353031

Herbal medicine for low back pain.

PubMed

Gagnier, J J; van Tulder, M; Berman, B; Bombardier, C

2006-04-19

Low-back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients with chronic low-back pain use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in low-back pain. To determine the effectiveness of herbal medicine for non-specific low-back pain. We searched the following electronic databases: Cochrane Complementary Medicine Field Trials Register (Issue 3, 2005), MEDLINE (1966 to July 2005), EMBASE (1980 to July 2005); checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this very specialized area. We included randomized controlled trials, examining adults (over 18 years of age) suffering from acute, sub-acute or chronic non-specific low-back pain. The interventions were herbal medicines, defined as plants that are used for medicinal purposes in any form. Primary outcome measures were pain and function. Two authors (JJG & MVT) conducted the database searches. One author contacted content experts and acquired relevant citations. Full references and abstracts of the identified studies were downloaded. A hard copy was retrieved for final inclusion decisions. Methodological quality and clinical relevance were assessed separately by two individuals. Disagreements were resolved by consensus. Ten trials were included in this review. Two high quality trials examining the effects of Harpagophytum Procumbens (Devil's Claw) found strong evidence that daily doses standardized to 50 mg or 100 mg harpagoside were better than placebo for short-term improvements in pain and rescue medication. Another high quality trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx). Two trials examining the effects of Salix Alba (White Willow Bark) found moderate evidence that daily doses standardized to 120 mg or 240 mg salicin were better than placebo for short-term improvements in pain and rescue medication. An additional trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib. Three low quality trials on Capsicum Frutescens (Cayenne), examining various topical preparations, found moderate evidence that Capsicum Frutescens produced more favourable results than placebo and one trial found equivalence to a homeopathic ointment. Harpagophytum Procumbens, Salix Alba and Capsicum Frutescens seem to reduce pain more than placebo. Additional trials testing these herbal medicines against standard treatments are needed. The quality of reporting in these trials was generally poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.

Advancing Survivors' Knowledge (ASK) about skin cancer study: study protocol for a randomized controlled trial.

PubMed

Daniel, Casey L; Armstrong, Gregory T; Keske, Robyn R; Davine, Jessica A; McDonald, Aaron J; Sprunck-Harrild, Kim M; Coleman, Catherine; Haneuse, Sebastien J; Mertens, Ann C; Emmons, Karen M; Marghoob, Ashfaq A; Elkin, Elena B; Dusza, Stephen W; Robison, Leslie L; Geller, Alan C

2015-03-24

Advances in treatment have increased childhood cancer 5-year survival rates to greater than 80%. However, children previously treated with radiation are at significantly increased risk of developing subsequent neoplasms, the most common of which are skin cancers. The National Cancer Institute and Children's Oncology Group have issued recommendations for survivors treated with radiation to perform monthly skin self-examinations and receive a physician skin examination at least annually, as early detection has demonstrated markedly improved outcomes in the diagnosis and treatment of skin cancers. The goal of the present study is to increase rates of skin self-examinations and clinical skin examinations among adult survivors of childhood cancer treated with radiation. This randomized controlled trial uses a 3-group comparative effectiveness design comparing: (1) Patient Activation and Education (PAE) including text messaging, print and web-based tutorials over 12 months; (2) PAE plus physician activation (PAE + MD) adding physician activation/educational materials about survivors' increased skin cancer risk and conducting full-body skin exams; and (3) PAE plus physician activation, plus teledermoscopy (PAE + MD + TD) adding participant receipt of a dermatoscope intended to empower them to photograph suspect moles or lesions for review by the study dermatologist. The current study addresses barriers to screening in this population by providing educational and motivational information for both survivors and physicians regarding the value of periodic skin examinations. It also utilizes innovative mobile health technology to encourage and motivate (that is activate) survivors to conduct skin self-examinations, request physician exams, and obtain treatment when worrisome lesions are found. Finally, as a comparative effectiveness trial, this study isolates the effects of adding specific components to the patient activation intervention to test the most effective intervention for enhancing skin examination vigilance among this high-risk group. Clinicaltrials.gov: NCT02046811 ; Registration date: 22 January 2014.

Design and challenges for a randomized, multi-site clinical trial comparing the use of service dogs and emotional support dogs in Veterans with post-traumatic stress disorder (PTSD).

PubMed

Saunders, Gabrielle H; Biswas, Kousick; Serpi, Tracey; McGovern, Stephanie; Groer, Shirley; Stock, Eileen M; Magruder, Kathryn M; Storzbach, Daniel; Skelton, Kelly; Abrams, Thad; McCranie, Mark; Richerson, Joan; Dorn, Patricia A; Huang, Grant D; Fallon, Michael T

2017-11-01

Posttraumatic stress disorder (PTSD) is a leading cause of impairments in quality of life and functioning among Veterans. Service dogs have been promoted as an effective adjunctive intervention for PTSD, however published research is limited and design and implementation flaws in published studies limit validated conclusions. This paper describes the rationale for the study design, a detailed methodological description, and implementation challenges of a multisite randomized clinical trial examining the impact of service dogs on the on the functioning and quality of life of Veterans with PTSD. Trial design considerations prioritized participant and intervention (dog) safety, selection of an intervention comparison group that would optimize enrollment in all treatment arms, pragmatic methods to ensure healthy well-trained dogs, and the selection of outcomes for achieving scientific and clinical validity in a Veteran PTSD population. Since there is no blueprint for conducting a randomized clinical trial examining the impact of dogs on PTSD of this size and scope, it is our primary intent that the successful completion of this trial will set a benchmark for future trial design and scientific rigor, as well as guiding researchers aiming to better understand the role that dogs can have in the management of Veterans experiencing mental health conditions such as PTSD. Published by Elsevier Inc.

Gut-directed hypnotherapy for functional abdominal pain or irritable bowel syndrome in children: a systematic review.

PubMed

Rutten, Juliette M T M; Reitsma, Johannes B; Vlieger, Arine M; Benninga, Marc A

2013-04-01

Gut directed hypnotherapy (HT) is shown to be effective in adult functional abdominal pain (FAP) and irritable bowel syndrome (IBS) patients. We performed a systematic review to assess efficacy of HT in paediatric FAP/IBS patients. We searched Medline, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature databases and Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) in children with FAP or IBS, investigating efficacy of HT on the following outcomes: abdominal pain scores, quality of life, costs and school absenteeism. Three RCT comparing HT to a control treatment were included with sample sizes ranging from 22 to 52 children. We refrained from statistical pooling because of low number of studies and many differences in design and outcomes. Two studies examined HT performed by a therapist, one examined HT through self-exercises on audio CD. All trials showed statistically significantly greater improvement in abdominal pain scores among children receiving HT. One trial reported beneficial effects sustained after 1 year of follow-up. One trial reported statistically significant improvement in quality of life in the HT group. Two trials reported significant reductions in school absenteeism after HT. Therapeutic effects of HT seem superior to standard medical care in children with FAP or IBS. It remains difficult to quantify exact benefits. The need for more high quality research is evident.

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

PubMed

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

2011-09-01

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

Prostate-specific antigen screening in a high-risk population: lessons from the community and how they relate to large-scale population-based studies.

PubMed

Shelton, Jeremy B; Barocas, Daniel A; Conway, Frances; Hart, Kathleen; Nelson, Kinloch; Richstone, Lee; Gonzalez, Ricardo R; Raman, Jay D; Scherr, Douglas S

2005-05-01

To estimate the incidence of prostate cancer among African-American men and Caribbean immigrants to the United States, to assess the applicability of large-scale prostate screening trials to a community screening program, and to recruit unscreened men. African-American and Caribbean-American men were targeted with a community-based prostate cancer screening program in Jamaica, New York. Serum prostate-specific antigen determination and digital rectal examination were used to determine abnormal findings. The incidence of an abnormal screening examination was used to project the incidence of prostate cancer, which was compared with that in other reported trials. The projected incidence of prostate cancer among African-Americans and Caribbean-Americans older than 50 years was 8% and 7%, respectively, similar to that reported in other trials of African-American men. The projected incidence of prostate cancer in Caribbean-American men aged 40 to 49 years was 1%, the same as the high rate reported among Caribbean men. As in other trials, a family history of prostate cancer and age were strong predictors of abnormal findings. Of the recruited men older than 50 years, 58% had never been screened compared with 42% nationally. Large population-based screening trials have identified ethnic groups at high risk of prostate cancer. This trial detected high rates of abnormal screening findings by targeting ethnicity. The incidence of an abnormal examination was high in Caribbean-American men younger than 50 years old. Finally, this trial successfully recruited underscreened men.

A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial.

PubMed

Niikura, Ryota; Nagata, Naoyoshi; Yamada, Atsuo; Doyama, Hisashi; Shiratori, Yasutoshi; Nishida, Tsutomu; Kiyotoki, Shu; Yada, Tomoyuki; Fujita, Tomoki; Sumiyoshi, Tetsuya; Hasatani, Kenkei; Mikami, Tatsuya; Honda, Tetsuro; Mabe, Katsuhiro; Hara, Kazuo; Yamamoto, Katsumi; Takeda, Mariko; Takata, Munenori; Tanaka, Mototsugu; Shinozaki, Tomohiro; Fujishiro, Mitsuhiro; Koike, Kazuhiko

2018-04-03

The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.

Comparison of Survival Outcomes Among Cancer Patients Treated In and Out of Clinical Trials

PubMed Central

2014-01-01

Background Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, “real-world” patients with respect to presenting characteristics and survival. Methods We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. Results We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. Conclusions Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials. PMID:24627276

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

Do brief motivational interventions reduce drinking game frequency in mandated students? An analysis of data from two randomized controlled trials.

PubMed

Fernandez, Anne C; Yurasek, Ali M; Merrill, Jennifer E; Miller, Mary Beth; Zamboanga, Byron L; Carey, Kate B; Borsari, Brian

2017-02-01

College students frequently engage in drinking games (DGs) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMIs) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from 2 randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Do Brief Motivational Interventions Reduce Drinking Game Frequency in Mandated Students? An analysis of data from two randomized controlled trials

PubMed Central

Fernandez, Anne C.; Yurasek, Allison M.; Merrill, Jennifer E.; Miller, Mary Beth; Zamboanga, Byron L.; Carey, Kate B.; Borsari, Brian

2016-01-01

Purpose College students frequently engage in drinking games (DG) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMI) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from two randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Methods Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Results Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both Trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Conclusions Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. PMID:27936818

Efficacy of physical exercise in preventing falls in older adults with cognitive impairment: a systematic review and meta-analysis.

PubMed

Chan, Wai Chi; Yeung, Jerry Wing Fai; Wong, Corine Sau Man; Lam, Linda Chiu Wa; Chung, Ka Fai; Luk, James Ka Hay; Lee, Jenny Shun Wah; Law, Andrew Chi Kin

2015-02-01

Numerous studies have reported the prevention of falls through exercise among cognitively healthy older people. This study aimed to determine whether the current evidence supports that physical exercise is also efficacious in preventing falls in older adults with cognitive impairment. Two independent reviewers searched MEDLINE; EMBASE; PsycINFO; the Cumulative Index to Nursing & Allied Health Literature; the Cochrane Central Register of Controlled Trials; the Cochrane Bone, Joint, and Muscle Trauma Group Specialized Register; ClinicalTrials.gov; and the UK Clinical Research Network Study Portfolio up to July 2013 without language restriction. We included randomized controlled trials that examined the efficacy of physical exercise in older adults with cognitive impairment. The methodological qualities of the included trials were appraised according to the criteria developed for the Cochrane review of fall prevention trials. The primary outcome measure was the rate ratio of falls. A meta-analysis was performed to estimate the pooled rate ratio and summarize the results of the trials on fall prevention through physical exercise. Seven randomized controlled trials involving 781 participants were included, 4 of which examined solely older people with cognitive impairment. Subgroup data on persons with cognitive impairment were obtained from the other 3 trials that targeted older populations in general. The meta-analysis showed that physical exercise had a significant effect in preventing falls in older adults with cognitive impairment, with a pooled estimate of rate ratio of 0.68 (95% confidence interval 0.51-0.91). The present analysis suggests that physical exercise has a positive effect on preventing falls in older adults with cognitive impairment. Further studies will be required to determine the modality and frequency of exercise that are optimal for the prevention of falls in this population. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Systematic review of herbs and dietary supplements for glycemic control in diabetes.

PubMed

Yeh, Gloria Y; Eisenberg, David M; Kaptchuk, Ted J; Phillips, Russell S

2003-04-01

To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.

Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective.

PubMed

Bollyky, Jennifer B; Xu, Ping; Butte, Atul J; Wilson, Darrell M; Beam, Craig A; Greenbaum, Carla J

2015-09-01

Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies. Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey. Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children. The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

PubMed Central

2010-01-01

Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders. Trial registration ClinicalTrials.gov NCT00052078. PMID:20051130

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians’ Patient Care Decisions

PubMed Central

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians. PMID:28269867

Serious adverse events in randomized psychosocial treatment studies: Safety or Arbitrary Edicts?

PubMed Central

Petry, Nancy M.; Roll, John M.; Rounsaville, Bruce J.; Ball, Samuel A.; Stitzer, Maxine; Peirce, Jessica M.; Blaine, Jack; Kirby, Kimberly C.; McCarty, Dennis; Carroll, Kathleen M.

2009-01-01

Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies. This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network. Substance abusing participants (N=1,687) were randomized to standard care or standard care plus either contingency management or motivational enhancement. Twelve percent of participants experienced one or more SAEs during the 27,198 person-weeks of follow-up. Of the 260 SAEs recorded, none were judged by the Data Safety Monitoring Board to be study related, and there were no significant differences between experimental and control conditions in SAE incidence rates. These data underscore the need to reconsider the rationale behind, and appropriate methods for, monitoring safety during psychosocial therapy trials. PMID:19045975

Primary care research: difficulties recruiting preschool children to clinical trials.

PubMed

Chadwick, B L; Treasure, E T

2005-05-01

The aims of the present study were to report difficulties experienced recruiting preschool children to a clinical trial and to report the acceptability of a dental intervention to their parents. The study was a randomized controlled trial (RCT). The study took place in community dental clinics, health centres and patient homes. Health visitors were used to recruit 508 children aged between 18 and 30 months from high caries areas of South Wales. Children with caries-free first primary molars were entered into a placebo-controlled individual RCT of fissure sealants. All children received a standard package of dental health education. Children in the test group had their first primary molars sealed with glass ionomer. All children were reviewed once. Families were asked to rate the acceptability of procedures. Health visitors referred 1228 children for screening, but only 547 were seen (44.5%) and 508 subjects were recruited to the trial. Of these, 449 (88.4%) were seen at follow-up. Some 667 children missed 1610 visits at baseline, and 373 of those recruited missed an appointment. At follow-up, 1056 appointments were staffed to review 449 children. Three-quarters of parents reported the examination to be very easy. Preschool children are difficult to access for community trials. Dental examinations and sealant placement were acceptable to the majority of families who were seen.

Bayesian network meta-analysis for cluster randomized trials with binary outcomes.

PubMed

Uhlmann, Lorenz; Jensen, Katrin; Kieser, Meinhard

2017-06-01

Network meta-analysis is becoming a common approach to combine direct and indirect comparisons of several treatment arms. In recent research, there have been various developments and extensions of the standard methodology. Simultaneously, cluster randomized trials are experiencing an increased popularity, especially in the field of health services research, where, for example, medical practices are the units of randomization but the outcome is measured at the patient level. Combination of the results of cluster randomized trials is challenging. In this tutorial, we examine and compare different approaches for the incorporation of cluster randomized trials in a (network) meta-analysis. Furthermore, we provide practical insight on the implementation of the models. In simulation studies, it is shown that some of the examined approaches lead to unsatisfying results. However, there are alternatives which are suitable to combine cluster randomized trials in a network meta-analysis as they are unbiased and reach accurate coverage rates. In conclusion, the methodology can be extended in such a way that an adequate inclusion of the results obtained in cluster randomized trials becomes feasible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Importance and Role of Intracluster Correlations in Planning Cluster Trials

PubMed Central

Preisser, John S.; Reboussin, Beth A.; Song, Eun-Young; Wolfson, Mark

2008-01-01

There is increasing recognition of the critical role of intracluster correlations of health behavior outcomes in cluster intervention trials. This study examines the estimation, reporting, and use of intracluster correlations in planning cluster trials. We use an estimating equations approach to estimate the intracluster correlations corresponding to the multiple-time-point nested cross-sectional design. Sample size formulae incorporating 2 types of intracluster correlations are examined for the purpose of planning future trials. The traditional intracluster correlation is the correlation among individuals within the same community at a specific time point. A second type is the correlation among individuals within the same community at different time points. For a “time × condition” analysis of a pretest–posttest nested cross-sectional trial design, we show that statistical power considerations based upon a posttest-only design generally are not an adequate substitute for sample size calculations that incorporate both types of intracluster correlations. Estimation, reporting, and use of intracluster correlations are illustrated for several dichotomous measures related to underage drinking collected as part of a large nonrandomized trial to enforce underage drinking laws in the United States from 1998 to 2004. PMID:17879427

Sincere but naive: methodological queries concerning the British Columbia polygamy reference trial.

PubMed

Ashley, Sean Matthew

2014-11-01

Academics frequently serve as expert witnesses in legal cases, yet their role as transmitters of social scientific knowledge remains under-examined. The present study analyzes the deployment of social science within British Columbia's polygamy reference trial where research is used to support the assertion that polygamy is inherently harmful to society. Within the trial record and the written decision, the protection of monogamy as an institution is performed in part through the marginalization of qualitative methodology and the concurrent privileging of quantitative studies that purportedly demonstrate widespread social harms associated with the practice of polygyny.

The Impact of Classroom Physical Activity Breaks on Middle School Students' Health-Related Fitness: An Xbox One Kinetic Delivered 4-Week Randomized Controlled Trial

ERIC Educational Resources Information Center

Yli-Piipari, S.; Layne, T.; McCollins, T.; Knox, T.

2016-01-01

The aim of the study was to examine the effect of a 4-week classroom physical activity break intervention on middle school students' health-related physical fitness. The study was a randomized controlled trial with students assigned to the experiment and control conditions. A convenience sample comprised 94 adolescents (experiment group n = 52;…

A survey of study participants' understanding of informed consent to participate in a randomised controlled trial of acupuncture.

PubMed

Smith, Caroline A; Fogarty, Sarah

2016-01-12

It is important that potential study participants are appropriately informed and understand what is involved with their research participation. A few studies have examined study participants' understanding of the informed consent process and the adequacy of the information they received when agreeing to participate in a randomised controlled trial. Deficiencies in the consent process have been found. This topic remains an under researched area of acupuncture research. The aim of this study was to examine participants' understanding of their informed consent and the adequacy of the information presented when agreeing to participate in a randomised controlled trial of acupuncture. All women who participated in a randomised controlled trial over an 11 month period were invited to participate in a survey. An anonymous self-completion questionnaire was designed and covered participants' understanding of informed consent in the clinical trial, their views of the information provided, the opportunity to ask questions, the use of sham acupuncture, their recall of study visits and processes for withdrawal, and their reason for participating in the trial. A response rate of 59% was obtained. Over 90% of subjects indicated there was plenty of opportunity to discuss the study prior to giving consent, and 89% indicated that questions asked were answered to their satisfaction. The majority of women indicated the amount of information describing acupuncture was about right, however 24% would have liked more. Information describing sham acupuncture was not considered adequate by 48% of women, and 35% would have liked more information, 30% could not recall why, or were uncertain why a sham group was used. Participants indicated less understanding of the information relating to payment if they became ill due to study participation, risks and discomforts from the study interventions, which of the procedures were experimental and for how long they would be involved in the study. Trial participants' understanding of informed consent was overall satisfactory but highlighted some areas of deficiency. Future studies could consider use of supplementary material such as Q and A fact sheets.

Examining the Impact of Technology on Primary Students' Revision of Written Work

ERIC Educational Resources Information Center

Lisy, Jennifer Garrette

2015-01-01

Few studies have examined the revision processes of second grade students and even fewer have explored the impact of digital writing on young students' revisions. This study utilized a within subject crossover trial using randomized block assignment (AB | BA) for counterbalancing. This study sought to determine (1) whether revising on paper versus…

Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana.

PubMed

Toledo, Lauren; McLellan-Lemal, Eleanor; Henderson, Faith L; Kebaabetswe, Poloko M

2015-03-01

Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants' perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, placebo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants' knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.

Predictors of the sex offender civil commitment trial outcomes in New York State.

PubMed

Lu, Yunmei; Freeman, Naomi J; Sandler, Jeffrey C

2015-10-01

The present study analyzed sex offender civil management (i.e., civil commitment) legal proceedings in New York State and identified factors that predict trial results. Specifically, the current study compared a sample of 38 sex offenders who were released to the community after winning their civil management trials to 183 sex offenders who lost their civil management trials. Additionally, for the 183 sex offenders who lost their civil management trials, the current study compared 146 offenders who were ordered to inpatient civil commitment to 37 offenders who were deemed fit for civil management in the community. Results of the analyses indicated that sexual criminality, sexual deviance, and criminality involving child victims increased the likelihood of offenders both losing their civil management trial and being found to be in need of inpatient care, while the presence of variables associated with nonsexual criminality increased the likelihood of offenders both winning their civil management trials and being deemed fit for management in the community. The findings of this study provide guidance for psychiatric examiners who testify in civil management legal proceedings, as well as for legal professionals specializing in civil management cases. (c) 2015 APA, all rights reserved).

Serious mistakes in meta-analysis of homeopathic research

PubMed Central

Vithoulkas, G

2017-01-01

The article discussed the immanent problems of meta-analyses selecting a number of independent trials in homeopathy, within which, the purpose was to examine the effectiveness of homeopathic treatment. Our focus lied in clarifying that the complex effects of homeopathic treatment known from history and day-to-day practice have not been respected so far. The examination of most of the homeopathic trials showed that studies rarely account for homeopathic principles, in order to assess the effectiveness of the treatment. The main flaw was that trials reflect the point of view that the treatment with a specific remedy could be administered in a particular disease. However, homeopathy aims to treat the whole person, rather than the diseases and each case has to be treated individually with an individualized remedy. Furthermore, the commonly known events during the course of homeopathic treatment, such as “initial aggravation” and “symptom-shift” were not considered in almost all the studies. Thus, only few trials were eligible for meta-analyses, if at all. These and other factors were discussed and certain homeopathic principles were suggested to be respected in further trials. It is expected, that a better understanding of homeopathic principles would provide guidelines for homeopathic research, which are more acceptable to both homeopathy and conventional medicine. PMID:28255376

Increasing instructional efficiency by presenting additional stimuli in learning trials for children with autism spectrum disorders.

PubMed

Vladescu, Jason C; Kodak, Tiffany M

2013-12-01

The current study examined the effectiveness and efficiency of presenting secondary targets within learning trials for 4 children with an autism spectrum disorder. Specifically, we compared 4 instructional conditions using a progressive prompt delay. In 3 conditions, we presented secondary targets in the antecedent or consequence portion of learning trials, or in the absence of prompts and reinforcement. In the fourth condition (control), we did not include secondary targets in learning trials. Results replicate and extend previous research by demonstrating that the majority of participants acquired secondary targets presented in the antecedent and consequent events of learning trials. © Society for the Experimental Analysis of Behavior.

The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer.

PubMed

Henick, Brian S; Herbst, Roy S; Goldberg, Sarah B

2014-12-01

Immunotherapy is emerging as a powerful approach in cancer treatment. Preclinical data predicted the antineoplastic effects seen in clinical trials of programmed death-1 (PD-1) pathway inhibitors, as well as their observed toxicities. The results of early clinical trials are extraordinarily promising in several cancer types and have shaped the direction of ongoing and future studies. This review describes the biological rationale for targeting the PD-1 pathway with monoclonal antibodies for the treatment of cancer as a context for examining the results of early clinical trials. It also surveys the landscape of ongoing clinical trials and discusses their anticipated strengths and limitations. PD-1 pathway inhibition represents a new frontier in cancer immunotherapy, which shows clear evidence of activity in various tumor types including NSCLC and melanoma. Ongoing and upcoming trials will examine optimal combinations of these agents, which should further define their role across tumor types. Current limitations include the absence of a reliable companion diagnostic to predict likely responders, as well as lack of data in early-stage cancer when treatment has the potential to increase cure rates.

Cranberry Products for the Prophylaxis of Urinary Tract Infections in Pediatric Patients.

PubMed

Durham, Spencer H; Stamm, Pamela L; Eiland, Lea S

2015-12-01

To evaluate the existing data regarding the use of cranberry products for the prevention of urinary tract infections (UTIs) in pediatric patients. A literature search of Medline databases from 1966 to June 2015 was conducted. The databases were searched using the terms "pediatrics," "children," "cranberry," "cranberry juice," and "urinary tract infections." The identified trials were then searched for additional references applicable to this topic. A total of 8 clinical trials were identified that examined the use of cranberry products, mostly juice, for the prevention of UTIs in children. Three trials examined the use in otherwise healthy children. Five trials examined the use in pediatric patients with underlying urogenital abnormalities of which 2 compared cranberry to antibiotics. In healthy pediatric patients, cranberry use was associated with a reduction in the overall number of UTIs and a decrease in the number of antibiotic days per year for UTI treatment. In patients with urogenital abnormalities, results were conflicting, with some studies showing no reduction in UTIs compared with placebo, but others demonstrating a significant reduction. However, cranberry products had similar efficacy when compared with both cefaclor and trimethoprim. All studies used a wide variety of doses and frequencies of cranberry, making specific product recommendations difficult. Cranberry appears effective for the prevention of UTIs in otherwise healthy children and is at least as effective as antibiotics in children with underlying urogenital abnormalities. However, recommendations for cranberry dosing and frequency cannot be confidently made at this time. Larger, well-designed trials are recommended. © The Author(s) 2015.

The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

PubMed

Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L

2013-01-01

There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

Persistent overconfidence despite practice: the role of task experience in preschoolers' recall predictions.

PubMed

Lipko, Amanda R; Dunlosky, John; Merriman, William E

2009-06-01

In three experiments, preschoolers' ability to predict their picture recall was examined. Children studied 10 pictures, predicted how many they would recall, and then attempted to recall them. This study-prediction-recall trial was repeated multiple times with new pictures on each trial. In Experiment 1, children were overconfident on the initial trial, and this overconfidence persisted across three trials. In Experiment 2, children predicted either their own performance or another child's performance. Their predictions were overconfident across all trials regardless of whether they made predictions for themselves or for another child, suggesting that wishful thinking cannot fully account for their overconfidence. In Experiment 3, some children postdicted their previous recall performance prior to making each prediction. Although their postdictions were quite accurate, their predictions were still overconfident across five trials. Preschoolers' overconfidence was remarkably resistant to the repeated experience of recalling fewer pictures than the children had predicted. Even asking them to report the number that they recalled on a previous trial, which they could do accurately, did not cause them to lower their predictions across trials.

A Trial of the Objective Structured Practical Examination in Physiology at Melaka Manipal Medical College, India

ERIC Educational Resources Information Center

Abraham, Reem Rachel; Raghavendra, Rao; Surekha, Kamath; Asha, Kamath

2009-01-01

A single examination does not fulfill all the functions of assessment. The present study was undertaken to determine the reliability and student satisfaction regarding the objective structured practical examination (OSPE) as a method of assessment of laboratory exercises in physiology before implementing it in the forthcoming university…

Crowdsourcing as a novel technique for retinal fundus photography classification: analysis of images in the EPIC Norfolk cohort on behalf of the UK Biobank Eye and Vision Consortium.

PubMed

Mitry, Danny; Peto, Tunde; Hayat, Shabina; Morgan, James E; Khaw, Kay-Tee; Foster, Paul J

2013-01-01

Crowdsourcing is the process of outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing for the classification of retinal fundus photography. One hundred retinal fundus photograph images with pre-determined disease criteria were selected by experts from a large cohort study. After reading brief instructions and an example classification, we requested that knowledge workers (KWs) from a crowdsourcing platform classified each image as normal or abnormal with grades of severity. Each image was classified 20 times by different KWs. Four study designs were examined to assess the effect of varying incentive and KW experience in classification accuracy. All study designs were conducted twice to examine repeatability. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Without restriction on eligible participants, two thousand classifications of 100 images were received in under 24 hours at minimal cost. In trial 1 all study designs had an AUC (95%CI) of 0.701(0.680-0.721) or greater for classification of normal/abnormal. In trial 1, the highest AUC (95%CI) for normal/abnormal classification was 0.757 (0.738-0.776) for KWs with moderate experience. Comparable results were observed in trial 2. In trial 1, between 64-86% of any abnormal image was correctly classified by over half of all KWs. In trial 2, this ranged between 74-97%. Sensitivity was ≥ 96% for normal versus severely abnormal detections across all trials. Sensitivity for normal versus mildly abnormal varied between 61-79% across trials. With minimal training, crowdsourcing represents an accurate, rapid and cost-effective method of retinal image analysis which demonstrates good repeatability. Larger studies with more comprehensive participant training are needed to explore the utility of this compelling technique in large scale medical image analysis.

The Efficacy of Parent-Child Interaction Therapy with Chinese Families: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Sin, Tammy C. S.; Choi, Siu-yan

2015-01-01

Objective: This study aimed to examine the efficacy of the Parent-Child Interaction Therapy (PCIT) in Hong Kong Chinese families, using randomized controlled trial design. Methods: The participants included 111 Hong Kong Chinese parents with children aged 2--7 years old, who were randomized into the intervention group (n = 54) and control group (n…

Effects of Scenery, Lighting, Glideslope, and Experience on Timing the Landing Flare

ERIC Educational Resources Information Center

Palmisano, Stephen; Favelle, Simone; Sachtler, W. L.

2008-01-01

This study examined three visual strategies for timing the initiation of the landing flare based on perceptions of either: (a) a critical height above ground level; (b) a critical runway width angle ([psi]); or (c) a critical time-to-contact (TTC) with the runway. Visual displays simulated landing approaches with trial-to-trial variations in…

Presentation Modality and Proactive Interference in Children's Short-Term Memory.

ERIC Educational Resources Information Center

Douglas, Joan Delahanty

This study examined the role of visual and auditory presentation in memory encoding processes of 80 second-grade children, using the release-from-proactive-interference short-term memory (STM) paradigm. Words were presented over three trials within one of the presentation modes and one taxonomic category, followed by a fourth trial in which the…

Three Randomized Controlled Trials of Early Long-Chain Polyunsaturated Fatty Acid Supplementation on Means-End Problem Solving in 9-Month-Olds

ERIC Educational Resources Information Center

Drover, James; Hoffman, Dennis R.; Castaneda, Yolanda S.; Morale, Sarah E.; Birch, Eileen E.

2009-01-01

This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds. Participants included 229 infants from 3 randomized controlled trials. Children received either formula supplemented with docosahexaenoic acid and arachidonic acid, or a control formula…

Training Head Start Teachers to Conduct Trial-Based Functional Analysis of Challenging Behavior

ERIC Educational Resources Information Center

Rispoli, Mandy; Burke, Mack D.; Hatton, Heather; Ninci, Jennifer; Zaini, Samar; Sanchez, Lisa

2015-01-01

Trial-based functional analysis (TBFA) is a procedure for experimentally identifying the function of challenging behavior within applied settings. The purpose of this study was to examine the effects of a TBFA teacher-training package in the context of two Head Start centers implementing programwide positive behavior support (PWPBS). Four Head…

Effectiveness of Multidimensional Family Therapy with Higher Severity Substance-Abusing Adolescents: Report from Two Randomized Controlled Trials

ERIC Educational Resources Information Center

Henderson, Craig E.; Dakof, Gayle A.; Greenbaum, Paul E.; Liddle, Howard A.

2010-01-01

Objective: We used growth mixture modeling to examine heterogeneity in treatment response in a secondary analysis of 2 randomized controlled trials testing multidimensional family therapy (MDFT), an established evidence-based therapy for adolescent drug abuse and delinquency. Method: The first study compared 2 evidence-based adolescent substance…

Reducing Developmental Risk for Emotional/Behavioral Problems: A Randomized Controlled Trial Examining the Tools for Getting Along Curriculum

ERIC Educational Resources Information Center

Daunic, Ann P.; Smith, Stephen W.; Garvan, Cynthia W.; Barber, Brian R.; Becker, Mallory K.; Peters, Christine D.; Taylor, Gregory G.; Van Loan, Christopher L.; Li, Wei; Naranjo, Arlene H.

2012-01-01

Researchers have demonstrated that cognitive-behavioral intervention strategies--such as social problem solving--provided in school settings can help ameliorate the developmental risk for emotional and behavioral difficulties. In this study, we report the results of a randomized controlled trial of Tools for Getting Along (TFGA), a social…

Multisite Randomized Controlled Trial Examining Intelligent Tutoring of Structure Strategy for Fifth-Grade Readers

ERIC Educational Resources Information Center

Wijekumar, Kausalai; Meyer, Bonnie J. F.; Lei, Pui-Wa; Lin, Yu-Chu; Johnson, Lori A.; Spielvogel, James A.; Shurmatz, Kathryn M.; Ray, Melissa; Cook, Michael

2014-01-01

This article reports on a large scale randomized controlled trial to study the efficacy of a web-based intelligent tutoring system for the structure strategy designed to improve content area reading comprehension. The research was conducted with 128 fifth-grade classrooms within 12 school districts in rural and suburban settings. Classrooms within…

Training New Instructors to Implement Discrete Trial Teaching Strategies with Children with Autism in a Community-Based Intervention Program

ERIC Educational Resources Information Center

Downs, Andrew; Downs, Robyn Conley

2013-01-01

The effects of training and supervision on instructor knowledge and performance of discrete trial teaching (DTT) within three domains (DTT Technical Skills; Work Session Preparation/Conclusion; and Student Engagement/Management) were examined in this study. Eight undergraduate student instructors received an 8-[hour] training in DTT and support…

Efficacy of a Universal Parent Training Program (HOPE-20): Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Kwan, H. W.

2017-01-01

Objective: This study examined the efficacy of Hands-On Parent Empowerment-20 (HOPE-20) program. Methods: Eligible participants were parents residing in Hong Kong with target children aged 2 years attending nursery schools. Cluster randomized control trial was adopted, with 10 schools (110 participants) assigned to intervention group and 8 schools…

Transition to Work: Effects of Preparedness and Goal Construction on Employment and Depressive Symptoms

ERIC Educational Resources Information Center

Koivisto, Petri; Vuori, Jukka; Vinokur, Amiram D.

2010-01-01

This study examines the mediating role of employment preparedness in improving employment, mental health, and construction of work-life goals among young vocational school graduates who participated in the School-to-Work effectiveness trial. The trial included a 1-week intervention program that focused on enhancing employment preparedness. In this…

Increasing Instructional Efficiency by Presenting Additional Stimuli in Learning Trials for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Vladescu, Jason C.; Kodak, Tiffany M.

2013-01-01

The current study examined the effectiveness and efficiency of presenting secondary targets within learning trials for 4 children with an autism spectrum disorder. Specifically, we compared 4 instructional conditions using a progressive prompt delay. In 3 conditions, we presented secondary targets in the antecedent or consequence portion of…

Motivational Pathways to Leisure-Time Physical Activity Participation in Urban Physical Education: A Cluster-Randomized Trial

ERIC Educational Resources Information Center

Yli-Piipari, Sami; Layne, Todd; Hinson, Janet; Irwin, Carol

2018-01-01

Purpose: Grounded in the trans-contextual model of motivation framework, this cluster-randomized trial examined the effectiveness of an autonomy supportive physical education (PE) instruction on student motivation and physical activity (PA). Method: The study comprised six middle schools and 408 students (M[subscript age] = 12.29), with primary…

Differential Benefits of Memory Training for Minority Older Adults in the SeniorWISE Study

ERIC Educational Resources Information Center

McDougall, Graham J., Jr.; Becker, Heather; Pituch, Keenan; Acee, Taylor W.; Vaughan, Phillip W.; Delville, Carol L.

2010-01-01

Purpose: Cognitive training improves mental abilities in older adults, but the benefit to minority elders is unclear. We conducted a subgroup analysis of subjects in the SeniorWISE (Wisdom Is Simply Exploration) trial to examine this issue. Design and Methods: SeniorWISE was a Phase 3 randomized trial that enrolled 265 nondemented…

Podcasts and Mobile Assessment Enhance Student Learning Experience and Academic Performance

ERIC Educational Resources Information Center

Morris, Neil P.

2010-01-01

The aim of this study was to combine podcasts of lectures with mobile assessments (completed via SMS on mobile telephones) to assess the effect on examination performance. Students (n = 100) on a final year, research-led, module were randomly divided into equal sized control and trial groups. The trial group were given access to podcasts/mobile…

Effects of Check and Connect on Attendance, Behavior, and Academics: A Randomized Effectiveness Trial

ERIC Educational Resources Information Center

Maynard, Brandy R.; Kjellstrand, Elizabeth K.; Thompson, Aaron M.

2014-01-01

Objectives: This study examined the effects of Check & Connect (C&C) on the attendance, behavior, and academic outcomes of at-risk youth in a field-based effectiveness trial. Method: A multisite randomized block design was used, wherein 260 primarily Hispanic (89%) and economically disadvantaged (74%) students were randomized to treatment…

Intelligence and Persisting with Medication for Two Years: Analysis in a Randomised Controlled Trial

ERIC Educational Resources Information Center

Deary, Ian J.; Gale, Catharine R.; Stewart, Marlene C. W.; Fowkes, F. Gerald R.; Murray, Gordon D.; Batty, G. David; Price, Jacqueline F.

2009-01-01

The study examined whether verbal intelligence is associated with persisting to take medication for up to two years. The design is a prospective follow-up of compliance with taking medication in high-risk individuals participating in a randomised, placebo-controlled trial set in Central Scotland. Participants were 1993 people aged between 50 and…

A Validation Study of Early Adolescents' Pubertal Self-Assessments

ERIC Educational Resources Information Center

Schmitz, Katharine E.; Hovell, Melbourne F.; Nichols, Jeanne F.; Irvin, Veronica L.; Keating, Kristen; Simon, Gayle M.; Gehrman, Christine; Jones, Kenneth Lee

2004-01-01

This study aimed to determine whether self-assessed puberty is sufficiently reliable and valid to substitute for physician examination when feasibility of physician examination is low (e.g., behavioral research). Adolescents (convenience sample N = 178 endocrinology patients and N = 125 from educational trial; mean age 12.7 and 11.3 years,…

Prediction of Response to Treatment in a Randomized Clinical Trial of Couple Therapy: A 2-Year Follow-Up

ERIC Educational Resources Information Center

Baucom, Brian R.; Atkins, David C.; Simpson, Lorelei E.; Christensen, Andrew

2009-01-01

Many studies have examined pretreatment predictors of immediate posttreatment outcome, but few studies have examined prediction of long-term treatment response to couple therapies. Four groups of predictors (demographic, intrapersonal, communication, and other interpersonal) and 2 moderators (pretreatment severity and type of therapy) were…

Are randomised controlled trials positivist? Reviewing the social science and philosophy literature to assess positivist tendencies of trials of social interventions in public health and health services.

PubMed

Bonell, Chris; Moore, Graham; Warren, Emily; Moore, Laurence

2018-04-19

We have previously proposed that trials of social interventions can be done within a "realist" research paradigm. Critics have countered that such trials are irredeemably positivist and asked us to explain our philosophical position. We set out to explore what is meant by positivism and whether trials adhere to its tenets (of necessity or in practice) via a narrative literature review of social science and philosophical discussions of positivism, and of the trials literature and three case studies of trials. The philosophical literature described positivism as asserting: (1) the epistemic primacy of sensory information; (2) the requirement that theoretical terms equate with empirical terms; (3) the aim of developing universal laws; and (4) the unity of method between natural and social sciences. Regarding (1), it seems that rather than embodying the epistemic primacy of sensory data, randomised controlled trials (RCTs) of social interventions in health embrace an anti-positivist approach aiming to test hypotheses derived deductively from prior theory. Considering (2), while some RCTs of social interventions appear to limit theorisation to concepts with empirical analogues, others examine interventions underpinned by theories engaging with mechanisms and contextual contingencies not all of which can be measured. Regarding (3), while some trialists and reviewers in the health field do limit their role to estimating statistical trends as a mechanistic form of generalisation, this is not an inevitable feature of RCT-based research. Trials of social interventions can instead aim to generalise at the level of theory which specifies how mechanisms are contingent on context. In terms of (4), while RCTs are used to examine biomedical as well as social interventions in health, RCTs of social interventions are often distinctive in using qualitative analyses of data on participant accounts to examine questions of meaning and agency not pursued in the natural sciences. We conclude that the most appropriate paradigm for RCTs of social interventions is realism not positivism.

Contribution of creatine to protein homeostasis in athletes after endurance and sprint running.

PubMed

Tang, Fu-Chun; Chan, Chun-Chen; Kuo, Po-Ling

2014-02-01

Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running. Twelve male athletes (20.3 ± 1.4 y) performed two identical (65-70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine. Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements. The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.

Characteristics associated with willingness to participate in a randomized controlled behavioral clinical trial using home-based personal computers and a webcam.

PubMed

Dodge, Hiroko H; Katsumata, Yuriko; Zhu, Jian; Mattek, Nora; Bowman, Molly; Gregor, Mattie; Wild, Katherine; Kaye, Jeffrey A

2014-12-23

Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Increasing potential participants' familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. The trial was registered on 29 March 2012 at ClinicalTirals.gov (ID number NCT01571427).

"I will miss the study, God bless you all": participation in a nutritional chemoprevention trial.

PubMed

Moreno-Black, Geraldine; Shor-Posner, Gail; Miguez, Maria-Jose; Burbano, Ximena; O'Mellan, Sandra; Yovanoff, P

2004-01-01

Randomized controlled clinical trials are often considered to be the "gold standard" for health research. Consequently, understanding the reasons people participate in these trials, especially minority groups who are often under-represented in clinical trials, or populations who have chronic illnesses or abuse drugs, is salient for successful recruitment, retention, and project design. This paper describes the results of a study that was designed to examine some of the ways in which participants in a randomized double blind clinical trial perceived their participation in the clinical trial, and the reasons they gave for continuing in the study. All of the participants were individuals who were using drugs and were infected with the HIV-1 virus, and had participated in a chemoprevention trial. The data from an exit interview were analyzed thematically in order to reveal units of meaning concerning participation and continuation in the clinical trial. The analysis revealed 3 higher-level concepts, or themes, that guided participation: increased health awareness, personal enhancement, and sociability. The data clearly indicated that involvement and retention in the trial were directly related to the ways in which the participants interpreted the study, perceived the benefits they derived from participating, and imbued their participation with value so that it was important and relevant to their own perceptions of health, as well as personal and social well being.

Does Whole Grain Consumption Alter Gut Microbiota and Satiety?

PubMed Central

Cooper, Danielle N.; Martin, Roy J.; Keim, Nancy L.

2015-01-01

This review summarizes recent studies examining whole grain consumption and its effect on gut microbiota and satiety in healthy humans. Studies comparing whole grains to their refined grain counterparts were considered, as were studies comparing different grain types. Possible mechanisms linking microbial metabolism and satiety are described. Clinical trials show that whole grain wheat, maize, and barley alter the human gut microbiota, but these findings are based on a few studies that do not include satiety components, so no functional claims between microbiota and satiety can be made. Ten satiety trials were evaluated and provide evidence that whole oats, barley, and rye can increase satiety, whereas the evidence for whole wheat and maize is not compelling. There are many gaps in the literature; no one clinical trial has examined the effects of whole grains on satiety and gut microbiota together. Once understanding the impact of whole grains on satiety and microbiota is more developed, then particular grains might be used for better appetite control. With this information at hand, healthcare professionals could make individual dietary recommendations that promote satiety and contribute to weight control. PMID:27417768

Impact of Attending Physicians' Comments on Residents' Workloads in the Emergency Department: Results from Two J(^o^)PAN Randomized Controlled Trials.

PubMed

Kuriyama, Akira; Umakoshi, Noriyuki; Fujinaga, Jun; Kaihara, Toshie; Urushidani, Seigo; Kuninaga, Naoki; Ichikawa, Motohiro; Ienaga, Shinichiro; Sasaki, Akira; Ikegami, Tetsunori

2016-01-01

To examine whether peppy comments from attending physicians increased the workload of residents working in the emergency department (ED). We conducted two parallel-group, assessor-blinded, randomized trials at the ED in a tertiary care hospital in western Japan. Twenty-five residents who examined either ambulatory (J(^o^)PAN-1 Trial) or transferred patients (J(^o^)PAN-2 Trial) in the ED on weekdays. Participants were randomly assigned to groups that either received a peppy message such as "Hope you have a quiet day!" (intervention group) or did not (control group) from the attending physicians. Both trials were conducted from June 2014 through March 2015. For each trial, residents rated the number of patients examined during and the busyness and difficulty of their shifts on a 5-point Likert scale. A total of 169 randomizations (intervention group, 81; control group, 88) were performed for the J(^o^)PAN-1 Trial, and 178 (intervention group, 85; control group, 93) for the J(^o^)PAN-2 Trial. In the J(^o^)PAN-1 trial, no differences were observed in the number of ambulatory patients examined during their shifts (5.5 and 5.7, respectively, p = 0.48), the busyness of their shifts (2.8 vs 2.8; p = 0.58), or the difficulty of their shifts (3.1 vs 3.1, p = 0.94). However, in the J(^o^)PAN-2 trial, although busyness (2.8 vs 2.7; p = 0.40) and difficulty (3.1 vs 3.2; p = 0.75) were similar between groups, the intervention group examined more transferred patients than the control group (4.4 vs 3.9; p = 0.01). Peppy comments from attending physicians had a minimal jinxing effect on the workload of residents working in the ED. University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000017193 and UMIN000017194.

Risk based monitoring (RBM) tools for clinical trials: A systematic review.

PubMed

Hurley, Caroline; Shiely, Frances; Power, Jessica; Clarke, Mike; Eustace, Joseph A; Flanagan, Evelyn; Kearney, Patricia M

2016-11-01

In November 2016, the Integrated Addendum to ICH-GCP E6 (R2) will advise trial sponsors to develop a risk-based approach to clinical trial monitoring. This new process is commonly known as risk based monitoring (RBM). To date, a variety of tools have been developed to guide RBM. However, a gold standard approach does not exist. This review aims to identify and examine RBM tools. Review of published and grey literature using a detailed search-strategy and cross-checking of reference lists. This review included academic and commercial instruments that met the Organisation for Economic Co-operation and Development (OECD) classification of RBM tools. Ninety-one potential RBM tools were identified and 24 were eligible for inclusion. These tools were published between 2000 and 2015. Eight tools were paper based or electronic questionnaires and 16 operated as Service as a System (SaaS). Risk associated with the investigational medicinal product (IMP), phase of the clinical trial and study population were examined by all tools and suitable mitigation guidance through on-site and centralised monitoring was provided. RBM tools for clinical trials are relatively new, their features and use varies widely and they continue to evolve. This makes it difficult to identify the "best" RBM technique or tool. For example, equivalence testing is required to determine if RBM strategies directed by paper based and SaaS based RBM tools are comparable. Such research could be embedded within multi-centre clinical trials and conducted as a SWAT (Study within a Trial). Copyright © 2016 Elsevier Inc. All rights reserved.

Interventions for investigating and identifying the causes of stillbirth.

PubMed

Wojcieszek, Aleena M; Shepherd, Emily; Middleton, Philippa; Gardener, Glenn; Ellwood, David A; McClure, Elizabeth M; Gold, Katherine J; Khong, Teck Yee; Silver, Robert M; Erwich, Jan Jaap Hm; Flenady, Vicki

2018-04-30

Identification of the causes of stillbirth is critical to the primary prevention of stillbirth and to the provision of optimal care in subsequent pregnancies. A wide variety of investigations are available, but there is currently no consensus on the optimal approach. Given their cost and potential to add further emotional burden to parents, there is a need to systematically assess the effect of these interventions on outcomes for parents, including psychosocial outcomes, economic costs, and on rates of diagnosis of the causes of stillbirth. To assess the effect of different tests, protocols or guidelines for investigating and identifying the causes of stillbirth on outcomes for parents, including psychosocial outcomes, economic costs, and rates of diagnosis of the causes of stillbirth. We searched Cochrane Pregnancy and Childbirth's Trials Register (31 August 2017), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (15 May 2017). We planned to include randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. We planned to include studies published as abstract only, provided there was sufficient information to allow us to assess study eligibility. We planned to exclude cross-over trials.Participants included parents (including mothers, fathers, and partners) who had experienced a stillbirth of 20 weeks' gestation or greater.This review focused on interventions for investigating and identifying the causes of stillbirth. Such interventions are likely to be diverse, but could include:* review of maternal and family history, and current pregnancy and birth history;* clinical history of present illness;* maternal investigations (such as ultrasound, amniocentesis, antibody screening, etc.);* examination of the stillborn baby (including full autopsy, partial autopsy or noninvasive components, such as magnetic resonance imaging (MRI), computerised tomography (CT) scanning, and radiography);* umbilical cord examination;* placental examination including histopathology (microscopic examination of placental tissue); and* verbal autopsy (interviews with care providers and support people to ascertain causes, without examination of the baby).We planned to include trials assessing any test, protocol or guideline (or combinations of tests/protocols/guidelines) for investigating the causes of stillbirth, compared with the absence of a test, protocol or guideline, or usual care (further details are presented in the Background, see Description of the intervention).We also planned to include trials comparing any test, protocol or guideline (or combinations of tests/protocols/guidelines) for investigating the causes of stillbirth with another, for example, the use of a limited investigation protocol compared with a comprehensive investigation protocol. Two review authors assessed trial eligibility independently. We excluded five studies that were not RCTs. There were no eligible trials for inclusion in this review. There is currently a lack of RCT evidence regarding the effectiveness of interventions for investigating and identifying the causes of stillbirth. Seeking to determine the causes of stillbirth is an essential component of quality maternity care, but it remains unclear what impact these interventions have on the psychosocial outcomes of parents and families, the rates of diagnosis of the causes of stillbirth, and the care and management of subsequent pregnancies following stillbirth. Due to the absence of trials, this review is unable to inform clinical practice regarding the investigation of stillbirths, and the specific investigations that would determine the causes.Future RCTs addressing this research question would be beneficial, but the settings in which the trials take place, and their design, need to be given careful consideration. Trials need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should also be considered in any future trials.

Placebo group improvement in trials of pharmacotherapies for alcohol use disorders: a multivariate meta-analysis examining change over time.

PubMed

Del Re, A C; Maisel, Natalya; Blodgett, Janet C; Wilbourne, Paula; Finney, John W

2013-10-01

Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement. Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment. Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time. Similar to previous pharmacotherapy placebo research, substantial pretest to posttest placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.

Management of post traumatic stress disorder after childbirth: a review.

PubMed

Lapp, Leann K; Agbokou, Catherine; Peretti, Charles-Siegfried; Ferreri, Florian

2010-09-01

Prevalence and risk factors for the development of post traumatic stress disorder (PTSD) after childbirth is well described in the literature. However, its management and treatment has only begun to be investigated. The aim of this article is to describe the studies that examine the effects of interventions on PTSD after childbirth. MedLine, PILOTS, CINAHL and ISI Web of Science databases were systematically searched for randomised controlled trials, pilot studies and case studies using key words related to PTSD, childbirth, treatment and intervention. The reference lists of the retrieved articles were also used to supplement the search. A total of nine studies were retrieved. Seven studies that examined debriefing or counselling were identified; six randomised controlled trials and one pilot study. Also found were one case report describing the effects of cognitive behavioural therapy (CBT) on two women, and one pilot study of eye movement desensitisation and reprocessing (EMDR). Overall, there is limited evidence concerning the management of women with PTSD after childbirth. The results agree with the findings from the non-childbirth related literature: debriefing and counselling are inconclusively effective while CBT and EMDR may improve PTSD status but require investigation in controlled trials before conclusions could be drawn.

GetReal in mathematical modelling: a review of studies predicting drug effectiveness in the real world.

PubMed

Panayidou, Klea; Gsteiger, Sandro; Egger, Matthias; Kilcher, Gablu; Carreras, Máximo; Efthimiou, Orestis; Debray, Thomas P A; Trelle, Sven; Hummel, Noemi

2016-09-01

The performance of a drug in a clinical trial setting often does not reflect its effect in daily clinical practice. In this third of three reviews, we examine the applications that have been used in the literature to predict real-world effectiveness from randomized controlled trial efficacy data. We searched MEDLINE, EMBASE from inception to March 2014, the Cochrane Methodology Register, and websites of key journals and organisations and reference lists. We extracted data on the type of model and predictions, data sources, validation and sensitivity analyses, disease area and software. We identified 12 articles in which four approaches were used: multi-state models, discrete event simulation models, physiology-based models and survival and generalized linear models. Studies predicted outcomes over longer time periods in different patient populations, including patients with lower levels of adherence or persistence to treatment or examined doses not tested in trials. Eight studies included individual patient data. Seven examined cardiovascular and metabolic diseases and three neurological conditions. Most studies included sensitivity analyses, but external validation was performed in only three studies. We conclude that mathematical modelling to predict real-world effectiveness of drug interventions is not widely used at present and not well validated. © 2016 The Authors Research Synthesis Methods Published by John Wiley & Sons Ltd. © 2016 The Authors Research Synthesis Methods Published by John Wiley & Sons Ltd.

Perceived racial discrimination and adoption of health behaviors in hypertensive Black Americans: the CAATCH trial.

PubMed

Forsyth, Jessica M; Schoenthaler, Antoinette; Ogedegbe, Gbenga; Ravenell, Joseph

2014-02-01

Few studies examine psychosocial factors influencing the adoption of healthy behaviors among hypertensive patients. The effect of discrimination on health behaviors remains untested. To examine the influence of discrimination on adoption of healthy behaviors among low-income Black hypertensive patients. Black patients (N = 930) in community-based primary care practices enrolled in the CAATCH trial. Mixed effects regressions examined associations between perceived discrimination and change in medication adherence, diet, and physical activity from baseline to 12 months, controlling for intervention, gender, age, income, and education. Patients were low-income, high-school-educated, with a mean age of 57 years. Greater discrimination was associated with worse diet and lower medication adherence at baseline. Discrimination was associated with greater improvement in healthy eating behaviors over the course of the 12-month trial. Prior exposure to discrimination was associated with unhealthy behaviors at baseline, but did not negatively influence the adoption of health behaviors over time.

Competency to stand trial evaluations in a multicultural population: Associations between psychiatric, demographic, and legal factors.

PubMed

Paradis, Cheryl M; Owen, Elizabeth; Solomon, Linda Z; Lane, Benjamin; Gulrajani, Chinmoy; Fullar, Michael; Perry, Alan; Rai, Sasha; Lavy, Tamar; McCullough, Gene

2016-01-01

Data were examined from an archival sample of Competency to Stand Trial (CST) reports of 200 consecutive New York City pre-trial defendants evaluated over a five-month period. Approximately a fourth of defendants in the present study were immigrants; many required the assistance of interpreters. The examiners conducting the CST evaluation diagnosed approximately half of the defendants with a primary diagnosis of a psychotic disorder and deemed over half not competent. Examiners reached the same conclusion about competency in 96% of cases, about the presence of a psychotic disorder in 91% of cases, and affective disorder in 85% of cases. No significant differences between psychologists and psychiatrists were found for rates of competency/incompetency opinions. Compared to those deemed competent, defendants deemed not competent had significantly higher rates of prior psychiatric hospitalization and diagnosis of psychotic illness at the time of the CST evaluation but lower rates of reported substance abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Correlation of Cognitive and Social Outcomes among Children with Autism Spectrum Disorder in a Randomized Trial of Behavioral Intervention

ERIC Educational Resources Information Center

Locke, Jill; Rotheram-Fuller, Erin; Xie, Ming; Harker, Colleen; Mandell, David

2014-01-01

Although social impairments are considered the hallmark deficit of autism, many behavioral intervention studies rely on cognitive functioning as a primary outcome. Fewer studies have examined whether changes in cognition are associated with changes in social functioning. This study examined whether cognitive gains among 192 students from 47…

Aromatherapy for pain management in labour.

PubMed

Smith, Caroline A; Collins, Carmel T; Crowther, Caroline A

2011-07-06

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of aromatherapy for pain management in labour. To examine the effects of aromatherapy for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2010), The Cochrane Complementary Medicine Field's Trials Register (October 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 31 October 2010), CINAHL (1980 to 31 October 2010), the Australian and New Zealand Trials Registry (31 October 2010), Chinese Clinical Trial Register (31 October 2010), Current Controlled Trials (31 October 2010), ClinicalTrials.gov (31 October 2010), ISRCTN Register (31 October 2010), National Center for Complementary and Alternative Medicine (NCCAM) (31 October 2010) and the WHO International Clinical Trials Registry Platform (31 October 2010). Randomised controlled trials comparing aromatherapy with placebo, no treatment or other non-pharmacological forms of pain management in labour. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We included two trials (535 women) in the review. The trials found no difference between groups for the primary outcomes of pain intensity, assisted vaginal birth (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.48 to 2.28, one trial, 513 women; RR 0.83, 95% CI 0.06 to 11.70, one trial, 22 women), and caesarean section (RR 0.98, 95% CI 0.49 to 1.94, one trial, 513 women; RR 2.54, 95% CI 0.11 to 56.25, one trial, 22 women); there were more babies admitted to neonatal intensive care in the control group of one trial (RR 0.08, 95% CI 0.00 to 1.42, one trial, 513 women) but this difference did not reach statistical significance. The trials found no differences between groups for the secondary outcomes of use of pharmacological pain relief (RR 0.35, 95% CI 0.04 to 3.32, one trial, 513 women; RR 2.50, 95% CI 0.31 to 20.45, one trial, 22 women), spontaneous vaginal delivery (RR 1.00, 95% CI 0.94 to 1.06, one trial, 513 women; RR 0.93, 95% CI 0.67 to 1.28, one trial, 22 women) or length of labour and augmentation (RR 1.14, 95% CI 0.90 to 1.45, one trial, 513 women). The risk of bias was low in the trials. There is a lack of studies evaluating the role of aromatherapy for pain management in labour. Further research is needed before recommendations can be made for clinical practice.

Interactive spaced-education to teach the physical examination: a randomized controlled trial.

PubMed

Kerfoot, B Price; Armstrong, Elizabeth G; O'Sullivan, Patricia N

2008-07-01

Several studies have documented that physical examination knowledge and skills are limited among medical trainees. The objective of the study is to investigate the efficacy and acceptability of a novel online educational methodology termed 'interactive spaced-education' (ISE) as a method to teach the physical examination. The design of the study is randomized controlled trial. All 170 second-year students in the physical examination course at Harvard Medical School were eligible to enroll. Spaced-education items (questions and explanations) were developed on core physical examination topics and were content-validated by two experts. Based on pilot-test data, 36 items were selected for inclusion. Students were randomized to start the 18-week program in November 2006 or 12 weeks later. Students were sent 6 spaced-education e-mails each week for 6 weeks (cycle 1) which were then repeated in two subsequent 6-week cycles (cycles 2 and 3). Students submitted answers to the questions online and received immediate feedback. An online end-of-program survey was administered. One-hundred twenty students enrolled in the trial. Cycles 1, 2, and 3 were completed by 88%, 76%, and 71% of students, respectively. Under an intent-to-treat analysis, cycle 3 scores for cohort A students [mean 74.0 (SD 13.5)] were significantly higher than cycle 1 scores for cohort B students [controls; mean 59.0 (SD 10.5); P < .001], corresponding to a Cohen's effect size of 1.43. Eighty-five percent of participants (102 of 120) recommended the ISE program for students the following year. ISE can generate significant improvements in knowledge of the physical examination and is very well-accepted by students.

A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network

PubMed Central

Roman, Paul M.; Abraham, Amanda J.; Rothrauff, Tanja C.; Knudsen, Hannah K.

2010-01-01

The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This paper focuses on three dimensions of the CTN’s organizational functioning. First, a longitudinal dataset is used to examine the CTN’s formation as a network of inter-organizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered inter-organizational interaction over time. Second, adoption of buprenorphine and motivational incentives among the CTN’s affiliated CTPs is identified over three waves of data. While adoption is found to increase with CTPs’ CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs’ pursuit of the CTN’s dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future. PMID:20307795

Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Forbes, Scott C.; Holroyd-Leduc, Jayna M.; Poulin, Marc J.; Hogan, David B.

2015-01-01

Background Observational studies have suggested that various nutrients, dietary supplements, and vitamins may delay the onset of age-associated cognitive decline and dementia. We systematically reviewed recent randomized controlled trials investigating the effect of nutritional interventions on cognitive performance in older non-demented adults. Methods We searched MEDLINE, CINAHL, Embase, and the Cochrane Library for articles published between 2003 and 2013. We included randomized trials of ≥ 3 months’ duration that examined the cognitive effects of a nutritional intervention in non-demented adults > 40 years of age. Meta-analyses were done when sufficient trials were available. Results Twenty-four trials met inclusion criteria (six omega-3 fatty acids, seven B vitamins, three vitamin E, eight other interventions). In the meta-analyses, omega-3 fatty acids showed no significant effect on Mini-Mental State Examination (MMSE) scores (four trials, mean difference 0.06, 95% CI −0.08 – 0.19) or digit span forward (three trials, mean difference −0.02, 95% CI −0.30 – 0.25), while B vitamins showed no significant effect on MMSE scores (three trials, mean difference 0.02, 95% CI −0.22 – 0.25). None of the vitamin E studies reported significant effects on cognitive outcomes. Among the other nutritional interventions, statistically significant differences between the intervention and control groups on at least one cognitive domain were found in single studies of green tea extract, Concord grape juice, chromium picolinate, beta-carotene, two different combinations of multiple vitamins, and a dietary approach developed for the control of hypertension. Conclusions Omega-3 fatty acids, B vitamins, and vitamin E supplementation did not affect cognition in non-demented middle-aged and older adults. Other nutritional interventions require further evaluation before their use can be advocated for the prevention of age-associated cognitive decline and dementia. PMID:26740832

The application of disease management to clinical trial designs.

PubMed

Puterman, Jared; Alter, David A

2009-08-01

The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.

Improving Diabetes care through Examining, Advising, and prescribing (IDEA): protocol for a theory-based cluster randomised controlled trial of a multiple behaviour change intervention aimed at primary healthcare professionals

PubMed Central

2014-01-01

Background New clinical research findings may require clinicians to change their behaviour to provide high-quality care to people with type 2 diabetes, likely requiring them to change multiple different clinical behaviours. The present study builds on findings from a UK-wide study of theory-based behavioural and organisational factors associated with prescribing, advising, and examining consistent with high-quality diabetes care. Aim To develop and evaluate the effectiveness and cost of an intervention to improve multiple behaviours in clinicians involved in delivering high-quality care for type 2 diabetes. Design/methods We will conduct a two-armed cluster randomised controlled trial in 44 general practices in the North East of England to evaluate a theory-based behaviour change intervention. We will target improvement in six underperformed clinical behaviours highlighted in quality standards for type 2 diabetes: prescribing for hypertension; prescribing for glycaemic control; providing physical activity advice; providing nutrition advice; providing on-going education; and ensuring that feet have been examined. The primary outcome will be the proportion of patients appropriately prescribed and examined (using anonymised computer records), and advised (using anonymous patient surveys) at 12 months. We will use behaviour change techniques targeting motivational, volitional, and impulsive factors that we have previously demonstrated to be predictive of multiple health professional behaviours involved in high-quality type 2 diabetes care. We will also investigate whether the intervention was delivered as designed (fidelity) by coding audiotaped workshops and interventionist delivery reports, and operated as hypothesised (process evaluation) by analysing responses to theory-based postal questionnaires. In addition, we will conduct post-trial qualitative interviews with practice teams to further inform the process evaluation, and a post-trial economic analysis to estimate the costs of the intervention and cost of service use. Discussion Consistent with UK Medical Research Council guidance and building on previous development research, this pragmatic cluster randomised trial will evaluate the effectiveness of a theory-based complex intervention focusing on changing multiple clinical behaviours to improve quality of diabetes care. Trial registration ISRCTN66498413. PMID:24886606

Efficacy of umbilical cord cleansing with a single application of 4% chlorhexidine for the prevention of newborn infections in Uganda: study protocol for a randomized controlled trial.

PubMed

Nankabirwa, Victoria; Tylleskär, Thorkild; Tumuhamye, Josephine; Tumwine, James K; Ndeezi, Grace; Martines, José C; Sommerfelt, Halvor

2017-07-12

Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness. The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat. This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis. ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015.

Safety and feasibility evaluation of tourniquets for total knee replacement (SAFE-TKR): study protocol.

PubMed

Wall, Peter Dh; Ahmed, Imran; Metcalfe, Andrew; Price, Andrew J; Seers, Kate; Hutchinson, Charles E; Parsons, Helen; Warwick, Jane; Rahman, Bushra; Brown, Jaclyn; Underwood, Martin

2018-04-10

This study is designed to determine whether a full randomised controlled trial (RCT) examining the clinical effectiveness and safety of total knee replacement surgery with or without a tourniquet is warranted and feasible. Single centre, patient-blinded and assessor-blinded RCT. A computer-generated randomisation service will allocate 50 participants into one of two trial treatments, surgery with or without a tourniquet. The primary objective is to estimate recruitment, crossovers and follow-up of patients. All patients will have an MRI scan of their brain preoperatively and day 1 or 2 postoperatively to identify ischaemic cerebral emboli (primary clinical outcome). Oxford Cognitive Screen, Montreal Cognitive Assessment and Mini-Mental State Examination will be evaluated as outcome tools for measuring cognitive impairment at days 1, 2 and 7 postoperatively. Thigh pain, blood transfusion requirements, venous thromboembolism, revision surgery, surgical complications, mortality and Oxford knee and five-level EuroQol-5D scores will be collected over 12 months. Integrated qualitative research study : 30 trial patients and 20 knee surgeons will take part in semistructured interviews. Interviews will capture views regarding the pilot trial and explore barriers and potential solutions to a full trial. Multicentre cohort study : UK National Joint Registry data will be linked to Hospital Episode Statistics to estimate the relationship between tourniquet use and venous thromboembolic event, length of hospital stay, risk of revision surgery and death. The study will conclude with a multidisciplinary workshop to reach a consensus on whether a full trial is warranted and feasible. National Research Ethics Committee (West Midlands-Edgbaston) approved this study on 27 January 2016 (15/WM/0455). The study is sponsored by University of Warwick and University Hospitals Coventry and Warwickshire. The results will be disseminated via high-impact peer-reviewed publication. ISRCTN20873088; Pre-results. © 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.

Characteristics of NIH- and industry-sponsored head and neck cancer clinical trials.

PubMed

Devaiah, Anand; Murchison, Charles

2016-09-01

Compare U.S. clinical trials sponsored by the National Institutes of Health (NIH) and industry, especially with regard to trial design, interventions studied, and results reporting rates. U.S. head and neck cancer clinical trials. We used information from ClinicalTrials.gov to compare NIH- and industry-sponsored head and neck cancer clinical trials, specifically analyzing differences in trial design and interventions studied. We examined publication rates and positive results rates using PubMed.gov. About 50% of NIH- and industry-sponsored clinical trials have their results reported in peer-reviewed literature. Industry-sponsored trials had higher rates of positive results than NIH-sponsored trials. NIH- and industry-sponsored clinical trials had similar trial designs, although industry-sponsored trials had significantly lower rates of randomization. Industry trials utilized radiation in 19% of trials and surgery in 2% of trials. NIH trials also had low utilization of both radiation and surgery (27% and 12% of trials, respectively). NIH- and industry-sponsored trials published their results in journals with comparable impact factors. There is significant underreporting of results in U.S. head and neck cancer clinical trials, whether sponsored by NIH or industry. Industry trials have significantly higher rates of positive results, although it is unclear what contributes to this. Both NIH- and industry-sponsored trials underutilize surgery and radiation as treatment modalities, despite the fact that these are standard-of-care therapies for head and neck cancer. We recommend that the NIH and industry report all results from clinical trials and use surgery and radiation as treatment arms in order to arrive at more balanced therapeutic recommendations. N/A. Laryngoscope, 126:E300-E303, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Systematic review of universal school-based resilience interventions targeting adolescent tobacco, alcohol or illicit drug use: review protocol

PubMed Central

Hodder, Rebecca Kate; Freund, Megan; Wolfenden, Luke; Bowman, Jenny; Gillham, Karen; Dray, Julia; Wiggers, John

2014-01-01

Introduction Tobacco, alcohol and illicit drug use contribute significantly to global rates of morbidity and mortality. Despite evidence suggesting interventions designed to increase adolescent resilience may represent a means of reducing adolescent substance use, and schools providing a key opportunity to implement such interventions, existing systematic reviews assessing the effectiveness of school-based interventions targeting adolescent substance use have not examined this potential. Methods and analysis The aim of the systematic review is to determine whether universal interventions focused on enhancing the resilience of adolescents are effective in reducing adolescent substance use. Eligible studies will: include participants 5–18 years of age; report tobacco use, alcohol consumption or illicit drug use as outcomes; and implement a school-based intervention designed to promote internal (eg, self-esteem) and external (eg, school connectedness) resilience factors. Eligible study designs include randomised controlled trials, cluster randomised controlled trials, staggered enrolment trials, stepped wedged trials, quasi-randomised trials, quasi-experimental trials, time series/interrupted time-series trials, preference trials, regression discontinuity trials and natural experiment studies with a parallel control group. A search strategy including criteria for participants, study design, outcome, setting and intervention will be implemented in various electronic databases and information sources. Two reviewers will independently screen studies to assess eligibility, as well as extract data from, and assess risk of bias of included studies. A third reviewer will resolve any discrepancies. Attempts will be made to quantify trial effects by meta-analysis. Binary outcomes will be pooled and effect size reported using ORs. For continuous data, effect size of trials will be reported using a mean difference where trial outcomes report the same outcome using a consistent measure, or standardised mean difference where trials report a comparable measure. Otherwise, trial outcomes will be described narratively. Dissemination Review findings will be disseminated via peer-reviewed journals and conferences. PMID:24861548

Proactive and reactive control depends on emotional valence: a Stroop study with emotional expressions and words.

PubMed

Kar, Bhoomika Rastogi; Srinivasan, Narayanan; Nehabala, Yagyima; Nigam, Richa

2018-03-01

We examined proactive and reactive control effects in the context of task-relevant happy, sad, and angry facial expressions on a face-word Stroop task. Participants identified the emotion expressed by a face that contained a congruent or incongruent emotional word (happy/sad/angry). Proactive control effects were measured in terms of the reduction in Stroop interference (difference between incongruent and congruent trials) as a function of previous trial emotion and previous trial congruence. Reactive control effects were measured in terms of the reduction in Stroop interference as a function of current trial emotion and previous trial congruence. Previous trial negative emotions exert greater influence on proactive control than the positive emotion. Sad faces in the previous trial resulted in greater reduction in the Stroop interference for happy faces in the current trial. However, current trial angry faces showed stronger adaptation effects compared to happy faces. Thus, both proactive and reactive control mechanisms are dependent on emotional valence of task-relevant stimuli.

Database trial impact on graduate nursing comprehensive exams

PubMed Central

Pionke, Katharine; Huckstadt, Alicia

2015-01-01

While the authors were doing a test period of databases, the question of whether or not databases affect outcomes of graduate nursing comprehensive examinations came up. This study explored that question through using citation analysis of exams that were taken during a database trial and exams that were not. The findings showed no difference in examination pass/fail rates. While the pass/fail rates did not change, a great deal was learned in terms of citation accuracy and types of materials that students used, leading to discussions about changing how citation and plagiarism awareness were taught. PMID:26512218

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527

PubMed Central

Foster, Jared C.; Seisler, Drew K.; Lafky, Jacqueline M.; Muss, Hyman B.; Cohen, Harvey J.; Mandelblatt, Jeanne; Winer, Eric P.; Hudis, Clifford A.; Partridge, Ann H.; Carey, Lisa A.; Cirrincione, Constance; Moreno-Aspitia, Alvaro; Kimmick, Gretchen; Jatoi, Aminah; Hurria, Arti

2017-01-01

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years (v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population. PMID:27992272

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527.

PubMed

Freedman, Rachel A; Foster, Jared C; Seisler, Drew K; Lafky, Jacqueline M; Muss, Hyman B; Cohen, Harvey J; Mandelblatt, Jeanne; Winer, Eric P; Hudis, Clifford A; Partridge, Ann H; Carey, Lisa A; Cirrincione, Constance; Moreno-Aspitia, Alvaro; Kimmick, Gretchen; Jatoi, Aminah; Hurria, Arti

2017-02-01

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

In "Step" with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study.

PubMed

Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.

Systematic reviews of randomised clinical trials examining the effects of psychotherapeutic interventions versus "no intervention" for acute major depressive disorder and a randomised trial examining the effects of "third wave" cognitive therapy versus mentalization-based treatment for acute major depressive disorder.

PubMed

Jakobsen, Janus Christian

2014-10-01

Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy and psychodynamic therapy may be effective treatment options for major depressive disorder, but the effects have only had limited assessment in systematic reviews. The two modern forms of psychotherapy, "third wave" cognitive therapy and mentalization-based treatment, have both gained some ground as treatments of psychiatric disorders. No randomised trial has compared the effects of these two interventions for major depressive disorder. We performed two systematic reviews with meta-analyses and trial sequential analyses using The Cochrane Collaboration methodology examining the effects of cognitive therapy and psycho-dynamic therapy for major depressive disorder. We developed a thorough treatment protocol for a randomised trial with low risks of bias (systematic error) and low risks of random errors ("play of chance") examining the effects of third wave' cognitive therapy versus mentalization-based treatment for major depressive disorder. We conducted a randomised trial according to good clinical practice examining the effects of "third wave" cognitive therapy versus mentalisation-based treatment for major depressive disorder. The first systematic review included five randomised trials examining the effects of psychodynamic therapy versus "no intervention' for major depressive disorder. Altogether the five trials randomised 365 participants who in each trial received similar antidepressants as co-interventions. All trials had high risk of bias. Four trials assessed "interpersonal psychotherapy" and one trial "short psychodynamic supportive psychotherapy". Both of these interventions are different forms of psychodynamic therapy. Meta-analysis showed that psychodynamic therapy significantly reduced depressive symptoms on the Hamilton Depression Rating Scale (HDRS) compared with "no intervention" (mean difference -3.01 (95% confidence interval -3.98 to -2.03; p = 0.00001), no significant heterogeneity between trials). Trial sequential analysis confirmed this result. The second systematic review included 12 randomised trials examining the effects of cognitive therapy versus "no intervention" for major depressive disorder. Altogether a total of 669 participants were randomised. All trials had high risk of bias. Meta-analysis showed that cognitive therapy significantly reduced depressive symptoms on the HDRS compared with "no intervention" (four trials; mean difference -3.05 (95% confidence interval, -5.23 to -0.87; p = 0.006)). Trial sequential analysis could not confirm this result. The trial protocol showed that it seemed feasible to conduct a randomised trial with low risks of bias and low risks of random errors examining the effects of "third wave" cognitive therapy versus mentalization-based therapy in a setting in the Danish healthcare system. It turned out to be much more difficult to recruit participants in the randomised trial than expected. We only included about half of the planned participants. The results from the randomised trial showed that participants randomised to "third wave" therapy compared with participants randomised to mentalization-based treatment had borderline significantly lower HDRS scores at 18 weeks in an unadjusted analysis (mean difference -4.14 score; 95% CI -8.30 to 0.03; p = 0.051). In the adjusted analysis, the difference was significant (p = 0.039). Five (22.7%) of the participants randomised to "third wave" cognitive therapy had remission at 18 weeks versus none of the participants randomised to mentalization-based treatment (p = 0.049). Sequential analysis showed that these findings could be due to random errors. No significant differences between the two groups was found regarding Beck's Depression Inventory (BDI II), Symptom Checklist 90 Revised (SCL 90-R), and The World Health Organization-Five Well-being Index 1999 (WHO 5). We concluded that cognitive therapy and psychodynamic therapy might be effective interventions for depression measured on HDRS and BDI, but the review results might be erroneous due to risks of bias and random errors. Furthermore, the effects seem relatively small. The trial protocol showed that it was possible to develop a protocol for a randomised trial examining the effects of "third wave" cognitive therapy versus mentalization-based treatment with low risks of bias and low risks of random errors. Our trial results showed that "third wave" cognitive therapy might be a more effective intervention for depressive symptoms measured on the HDRS compared with mentalization-based treatment. The two interventions did not seem to differ significantly regarding BDI II, SCL 90-R, and WHO 5. More randomised trials with low risks of bias and low risks of random errors are needed to assess the effects of cognitive therapy, psychodynamic therapy, "third wave" cognitive therapy, and mentalization-based treatment.

Examiner Training and Reliability in Two Randomized Clinical Trials of Adult Dental Caries

PubMed Central

Banting, David W.; Amaechi, Bennett T.; Bader, James D.; Blanchard, Peter; Gilbert, Gregg H.; Gullion, Christina M.; Holland, Jan Carlton; Makhija, Sonia K.; Papas, Athena; Ritter, André V.; Singh, Mabi L.; Vollmer, William M.

2013-01-01

Objectives This report describes the training of dental examiners participating in two dental caries clinical trials and reports the inter- and intra- examiner reliability scores from the initial standardization sessions. Methods Study examiners were trained to use a modified ICDAS-II system to detect the visual signs of non-cavitated and cavitated dental caries in adult subjects. Dental caries was classified as no caries (S), non-cavitated caries (D1), enamel caries (D2) and dentine caries (D3). Three standardization sessions involving 60 subjects and 3604 tooth surface calls were used to calculate several measures of examiner reliability. Results The prevalence of dental caries observed in the standardization sessions ranged from 1.4% to 13.5% of the coronal tooth surfaces examined. Overall agreement between pairs of examiners ranged from 0.88 to 0.99. An intra-class coefficient threshold of 0.60 was surpassed for all but one examiner. Inter-examiner unweighted kappa values were low (0.23– 0.35) but weighted kappas and the ratio of observed to maximum kappas were more encouraging (0.42– 0.83). The highest kappa values occurred for the S/D1 vs. D2/D3 two-level classification of dental caries, for which seven of the eight examiners achieved observed to maximum kappa values over 0.90.Intra-examiner reliability was notably higher than inter-examiner reliability for all measures and dental caries classification systems employed. Conclusion The methods and results for the initial examiner training and standardization sessions for two large clinical trials are reported. Recommendations for others planning examiner training and standardization sessions are offered. PMID:22320292

Examiner training and reliability in two randomized clinical trials of adult dental caries.

PubMed

Banting, David W; Amaechi, Bennett T; Bader, James D; Blanchard, Peter; Gilbert, Gregg H; Gullion, Christina M; Holland, Jan Carlton; Makhija, Sonia K; Papas, Athena; Ritter, André V; Singh, Mabi L; Vollmer, William M

2011-01-01

This report describes the training of dental examiners participating in two dental caries clinical trials and reports the inter- and intra-examiner reliability scores from the initial standardization sessions. Study examiners were trained to use a modified International Caries Detection and Assessment System II system to detect the visual signs of non-cavitated and cavitated dental caries in adult subjects. Dental caries was classified as no caries (S), non-cavitated caries (D1), enamel caries (D2), and dentine caries (D3). Three standardization sessions involving 60 subjects and 3,604 tooth surface calls were used to calculate several measures of examiner reliability. The prevalence of dental caries observed in the standardization sessions ranged from 1.4 percent to 13.5 percent of the coronal tooth surfaces examined. Overall agreement between pairs of examiners ranged from 0.88 to 0.99. An intra-class coefficient threshold of 0.60 was surpassed for all but one examiner. Inter-examiner unweighted kappa values were low (0.23-0.35), but weighted kappas and the ratio of observed to maximum kappas were more encouraging (0.42-0.83). The highest kappa values occurred for the S/D1 versus D2/D3 two-level classification of dental caries, for which seven of the eight examiners achieved observed to maximum kappa values over 0.90. Intra-examiner reliability was notably higher than inter-examiner reliability for all measures and dental caries classifications employed. The methods and results for the initial examiner training and standardization sessions for two large clinical trials are reported. Recommendations for others planning examiner training and standardization sessions are offered. © 2011 American Association of Public Health Dentistry.

Accelerating Preschoolers' Early Literacy Development through Classroom-Based Teacher-Child Storybook Reading and Explicit Print Referencing

ERIC Educational Resources Information Center

Justice, Laura M.; Kaderavek, Joan N.; Fan, Xitao; Sofka, Amy; Hunt, Aileen

2009-01-01

Purpose: This study examined the impact of teacher use of a print referencing style during classroom-based storybook reading sessions conducted over an academic year. Impacts on preschoolers' early literacy development were examined, focusing specifically on the domain of print knowledge. Method: This randomized, controlled trial examined the…

The impact of gender on treatment effectiveness of body psychotherapy for negative symptoms of schizophrenia: a secondary analysis of the NESS trial data

PubMed Central

Savill, Mark; Orfanos, Stavros; Bentall, Richard; Reininghaus, Ulrich; Wykes, Til; Priebe, Stefan

2016-01-01

Despite promising findings from small-scale studies suggesting that body psychotherapy may be an effective treatment for negative symptoms, these results were not replicated in a recent multisite trial. In this trial a far smaller proportion of women were recruited relative to earlier studies, which may be an issue given the gender mix of the sample evaluated has been found to affect trial outcomes in schizophrenia. Using data from our multisite trial, the interaction between gender and treatment allocation as a predictor of outcomes was examined in 275 participants (72 women and 203 men) randomised to either a body psychotherapy or Pilates group. Negative symptoms were found to significantly reduce in women randomised to the body psychotherapy condition in comparison to Pilates, while no such effect was detected in men. Consistent with the smaller trials, this improvement was found to relate predominantly to expressive deficits. These findings suggest that body psychotherapy may be an effective treatment for negative symptoms in women. These findings emphasise the importance of sample characteristics in determining trial outcome in psychological treatment studies. PMID:27871030

Preference in Random Assignment: Implications for the Interpretation of Randomized Trials

PubMed Central

Gold, Paul B.; Hargreaves, William A.; Aronson, Elliot; Bickman, Leonard; Barreira, Paul J.; Jones, Danson R.; Rodican, Charles F.; Fisher, William H.

2009-01-01

Random assignment to a preferred experimental condition can increase service engagement and enhance outcomes, while assignment to a less-preferred condition can discourage service receipt and limit outcome attainment. We examined randomized trials for one prominent psychiatric rehabilitation intervention, supported employment, to gauge how often assignment preference might have complicated the interpretation of findings. Condition descriptions, and greater early attrition from services-as-usual comparison conditions, suggest that many study enrollees favored assignment to new rapid-job-placement supported employment, but no study took this possibility into account. Reviews of trials in other service fields are needed to determine whether this design problem is widespread. PMID:19434489

Physical Examination-Indicated Cerclage: A Systematic Review and Meta-analysis.

PubMed

Ehsanipoor, Robert M; Seligman, Neil S; Saccone, Gabriele; Szymanski, Linda M; Wissinger, Christina; Werner, Erika F; Berghella, Vincenzo

2015-07-01

To estimate the effectiveness of physical examination-indicated cerclage in the setting of second-trimester cervical dilatation by systematic review and meta-analysis of published studies. We searched MEDLINE, EMBASE, Scopus, ClinicalTrials.gov, Web of Science, and the Cochrane Library for studies published between 1966 and 2014 that evaluated cervical cerclage for the treatment of cervical insufficiency. The search yielded 6,314 citations. We included cohort studies and randomized controlled trials comparing cerclage placement with expectant management of women with cervical dilatation between 14 and 27 weeks of gestation. Two investigators independently reviewed each citation for inclusion or exclusion and discordant decisions were arbitrated by a third reviewer. Summary estimates were reported as the mean difference and 95% confidence interval (CI) for continuous variables or relative risk and with 95% CI for dichotomous outcomes. Fixed- and random-effects meta-analysis was used, depending on heterogeneity. Ten studies met inclusion criteria and were included in the final analysis. One was a randomized controlled trial, two were prospective cohort studies, and the remaining seven were retrospective cohort studies. Of the 757 women, 485 (64%) underwent physical examination-indicated cerclage placement and 272 (36%) were expectantly managed. Cerclage was associated with increased neonatal survival (71% compared with 43%; relative risk 1.65, 95% CI 1.19-2.28) and prolongation of pregnancy (mean difference 33.98 days, 95% CI 17.88-50.08). Physical examination-indicated cerclage is associated with a significant increase in neonatal survival and prolongation of pregnancy of approximately 1 month when compared with no such cerclage. The strength of this conclusion is limited by the potential for bias in the included studies.

Feedback about More Accurate versus Less Accurate Trials: Differential Effects on Self-Confidence and Activation

ERIC Educational Resources Information Center

Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

2012-01-01

One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected by feedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On Day 1, participants performed a golf putting task under one of…

Examination of Individual Differences in Outcomes from a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory Training Programs

ERIC Educational Resources Information Center

Smith, Sherri L.; Saunders, Gabrielle H.; Chisolm, Theresa H.; Frederick, Melissa; Bailey, Beth A.

2016-01-01

Purpose: The purpose of this study was to determine if patient characteristics or clinical variables could predict who benefits from individual auditory training. Method: A retrospective series of analyses were performed using a data set from a large, multisite, randomized controlled clinical trial that compared the treatment effects of at-home…

Assessment Data-Informed Guidance to Individualize Kindergarten Reading Instruction: Findings from a Cluster-Randomized Control Field Trial

ERIC Educational Resources Information Center

Al Otaiba, Stephanie; Connor, Carol M.; Folsom, Jessica S.; Greulich, Luana; Meadows, Jane; Li, Zhi

2011-01-01

The purpose of this cluster-randomized control field trial was to examine whether kindergarten teachers could learn to differentiate classroom reading instruction using Individualized Student Instruction for Kindergarten (ISI-K) and to test the efficacy of differentiation on reading outcomes. The study involved 14 schools, 23 ISI-K (n = 305…

Near-Miss Effects on Response Latencies and Win Estimations of Slot Machine Players

ERIC Educational Resources Information Center

Dixon, Mark R.; Schreiber, James E.

2004-01-01

The present study examined the degree to which slot machine near-miss trials, or trials that displayed 2 of 3 winning symbols on the payoff line, affected response times and win estimations of 12 recreational slot machine players. Participants played a commercial slot machine in a casino-like laboratory for course extra-credit points. Videotaped…

Teacher Implementation of Trial-Based Functional Analysis and Differential Reinforcement of Alternative Behavior for Students with Challenging Behavior

ERIC Educational Resources Information Center

Flynn, Susan D.; Lo, Ya-yu

2016-01-01

The purpose of this study was to examine the effects of a training package on three middle school special education teachers' accurate implementation of trial-based functional analysis (TBFA) and differential reinforcement of alternative behavior (DRA) with their students with autism spectrum disorders or emotional and behavioral disorders in the…

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

ERIC Educational Resources Information Center

Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

2012-01-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

Reducing Conduct Problems among Children Exposed to Intimate Partner Violence: A Randomized Clinical Trial Examining Effects of Project Support

ERIC Educational Resources Information Center

Jouriles, Ernest N.; McDonald, Renee; Rosenfield, David; Stephens, Nanette; Corbitt-Shindler, Deborah; Miller, Pamela C.

2009-01-01

This study was a randomized clinical trial of Project Support, an intervention designed to reduce conduct problems among children exposed to intimate partner violence. Participants were 66 families (mothers and children) with at least 1 child exhibiting clinical levels of conduct problems. Families were recruited from domestic violence shelters.…

Effects of Error Correction during Assessment Probes on the Acquisition of Sight Words for Students with Moderate Intellectual Disabilities

ERIC Educational Resources Information Center

Waugh, Rebecca E.

2010-01-01

Simultaneous prompting is an errorless learning strategy designed to reduce the number of errors students make; however, research has shown a disparity in the number of errors students make during instructional versus probe trials. This study directly examined the effects of error correction versus no error correction during probe trials on the…

Effects of Error Correction during Assessment Probes on the Acquisition of Sight Words for Students with Moderate Intellectual Disabilities

ERIC Educational Resources Information Center

Waugh, Rebecca E.; Alberto, Paul A.; Fredrick, Laura D.

2011-01-01

Simultaneous prompting is an errorless learning strategy designed to reduce the number of errors students make; however, research has shown a disparity in the number of errors students make during instructional versus probe trials. This study directly examined the effects of error correction versus no error correction during probe trials on the…

Correlates of Adherence to a Telephone-Based Multiple Health Behavior Change Cancer Preventive Intervention for Teens: The Healthy for Life Program (HELP)

ERIC Educational Resources Information Center

Mays, Darren; Peshkin, Beth N.; Sharff, McKane E.; Walker, Leslie R.; Abraham, Anisha A.; Hawkins, Kirsten B.; Tercyak, Kenneth P.

2012-01-01

This study examined factors associated with teens' adherence to a multiple health behavior cancer preventive intervention. Analyses identified predictors of trial enrollment, run-in completion, and adherence (intervention initiation, number of sessions completed). Of 104 teens screened, 73% (n = 76) were trial eligible. White teens were more…

A Clustered Randomized Controlled Trial to Determine Impacts of the Harvest of the Month Program

ERIC Educational Resources Information Center

LaChausse, Robert G.

2017-01-01

The study purpose was to examine the impact of the Harvest of the Month (HOTM) program on fruit and vegetable (FV) consumption, FV preferences, other eating behaviors, physical activity and other variables related to healthy eating. A clustered randomized controlled trial was employed in 28 elementary schools. After parental consent was obtained,…

A Study of Specialty Clones’ Yield Performance in Early and Late Harvests

USDA-ARS?s Scientific Manuscript database

Technical Abstract: A study was conducted on specialty potato breeding lines to examine yield components in an early and late harvest. Upon first examination it was apparent that the early water cutoff had a large effect on total yield. In the early trial only one clone achieved 600 cwt/A of total...

Human striatal activation during adjustment of the response criterion in visual word recognition.

PubMed

Kuchinke, Lars; Hofmann, Markus J; Jacobs, Arthur M; Frühholz, Sascha; Tamm, Sascha; Herrmann, Manfred

2011-02-01

Results of recent computational modelling studies suggest that a general function of the striatum in human cognition is related to shifting decision criteria in selection processes. We used functional magnetic resonance imaging (fMRI) in 21 healthy subjects to examine the hemodynamic responses when subjects shift their response criterion on a trial-by-trial basis in the lexical decision paradigm. Trial-by-trial criterion setting is obtained when subjects respond faster in trials following a word trial than in trials following nonword trials - irrespective of the lexicality of the current trial. Since selection demands are equally high in the current trials, we expected to observe neural activations that are related to response criterion shifting. The behavioural data show sequential effects with faster responses in trials following word trials compared to trials following nonword trials, suggesting that subjects shifted their response criterion on a trial-by-trial basis. The neural responses revealed a signal increase in the striatum only in trials following word trials. This striatal activation is therefore likely to be related to response criterion setting. It demonstrates a role of the striatum in shifting decision criteria in visual word recognition, which cannot be attributed to pure error-related processing or the selection of a preferred response. Copyright © 2010 Elsevier Inc. All rights reserved.

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

PubMed Central

Detweiler, Mark B.; Pagadala, Bhuvaneshwar; Candelario, Joseph; Boyle, Jennifer S.; Detweiler, Jonna G.; Lutgens, Brian W.

2016-01-01

The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0–6.0 mg), clonidine (63%, 0.1–2.0 mg), quetiapine (50%, 12.5–800.0 mg), mirtazapine (50%; 7.5–30.0 mg), and terazosin (64%, 50.0–300.0 mg). Notably, olanzapine (2.5–10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares. PMID:27999253

Communication about the Risks and Benefits of Phase I Pediatric Oncology Trials

PubMed Central

Hazen, Rebecca A.; Zyzanski, Stephen; Baker, Justin; Drotar, Dennis; Kodish, Eric

2015-01-01

Introduction Phase 1 pediatric oncology trials offer only a small chance of direct benefit and may have significant risks and an impact on quality of life. To date, research has not examined discussions of risks and benefits during informed consent conferences for phase 1 pediatric oncology trials. The objective of the current study was to examine clinician and family communication about risks, benefits, and quality of life during informed consent conferences for phase 1 pediatric oncology trials. Methods Participants included clinician investigators, parents, and children recruited from 6 sites conducting phase 1 pediatric oncology trials. Eighty-five informed consent conferences were observed and audiotaped. Trained coders assessed discussions of risks, benefits, and quality of life. Types of risks discussed were coded (e.g., unanticipated risks, digestive system risks, death). Types of benefits were categorized as therapeutic (e.g. discussion of how participation may or may not directly benefit child), psychological, bridge to future trial, and altruism. Results Risks and benefits were discussed in 95% and 88% of informed consent conferences, respectively. Therapeutic benefit was the most frequently discussed benefit. The impact of trial participation on quality of life was discussed in the majority (88%) of informed consent conferences. Conclusion Therapeutic benefit, risks, and quality of life were frequently discussed. The range of information discussed during informed consent conferences suggests the need for considering a staged process of informed consent for phase 1 pediatric oncology trials. PMID:25638751

Understanding Study Participants Views on Co-Creation of Data and Use of EHR in Clinical Studies.

PubMed

Scott Duncan, Therese; Hägglund, Maria

2018-01-01

In order to increase clinical trial participation, the reasons for participating need to be observed. Since there is rather inadequate information concerning how individuals such as patients, decides to participate in clinical trials semi-structured interviews have been done. Examining the use of EHR in clinical trials and co-creation of data, the result showed that it is important for the researches to have access to the patients' EHR and for the patients to contribute with their own ideas of research. Important aspects of further participation in clinical trials were that it should be fun and informative. The patients agreed on that the effort of participating could decrease with the use of electronically collection and self-reporting of data, e.g. through a patient portal.

Antithrombotic therapy in peripheral artery disease: A review of the EUCLID trial results and current ongoing trials.

PubMed

Ward, Rachael; Long, Chandler; Patel, Manesh R; Jones, William S

2018-01-01

In addition to risk-factor modification, antithrombotic therapy is the hallmark of management to reduce cardiovascular ischemic events in patients with peripheral artery disease (PAD). Currently, the guidelines recommend long-term antiplatelet therapy with aspirin or clopidogrel in this patient population to reduce myocardial infarction, stroke, and vascular death. Past outcomes studies have shown some benefit of ticagrelor, another antiplatelet agent, as compared with clopidogrel in patients with coronary disease and concomitant PAD. However, most recently, the Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial has shown no additional benefit of ticagrelor over clopidogrel. In this trial, a minority of patients had concomitant coronary artery disease, making it unique to previous studies. The EUCLID trial's evidence of neutrality between clopidogrel and ticagrelor sheds light into the complexity of studying the PAD population and the continued need to meticulously design trials to investigate the optimal therapies. The topics that will be discussed in this review include the role of antiplatelet therapy in the management of patients with PAD, a review of the EUCLID trial results and the important factors to be considered in interpreting the surprising results, and promising recent ongoing clinical trials assessing therapies in the treatment of patients with PAD. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2017-08-01

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

Increased consumption of fruit and vegetables for the primary prevention of cardiovascular diseases.

PubMed

Hartley, Louise; Igbinedion, Ewemade; Holmes, Jennifer; Flowers, Nadine; Thorogood, Margaret; Clarke, Aileen; Stranges, Saverio; Hooper, Lee; Rees, Karen

2013-06-04

There is increasing evidence that high consumption of fruit and vegetables is beneficial for cardiovascular disease (CVD) prevention. The primary objective is to determine the effectiveness of i) advice to increase fruit and vegetable consumption ii) the provision of fruit and vegetables to increase consumption, for the primary prevention of CVD.  We searched the following electronic databases: The Cochrane Library (2012, issue 9-CENTRAL, HTA, DARE, NEED), MEDLINE (1946 to week 3 September 2012); EMBASE (1980 to 2012 week 39) and the Conference Proceedings Citation Index - Science on ISI Web of Science (5 October 2012). We searched trial registers, screened reference lists and contacted authors for additional information where necessary. No language restrictions were applied. Randomised controlled trials with at least three months follow-up (follow-up was considered to be the time elapsed since the start of the intervention) involving healthy adults or those at high risk of CVD. Trials investigated either advice to increase fruit and vegetable intake (via any source or modality) or the provision of fruit and vegetables to increase intake. The comparison group was no intervention or minimal intervention. Outcomes of interest were CVD clinical events (mortality (CVD and all-cause), myocardial infarction (MI), coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), angiographically-defined angina pectoris, stroke, carotid endarterectomy, peripheral arterial disease (PAD)) and major CVD risk factors (blood pressure, blood lipids, type 2 diabetes). Trials involving multifactorial lifestyle interventions (including different dietary patterns, exercise) or where the focus was weight loss were excluded to avoid confounding. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. Trials of provision of fruit and vegetables were analysed separately from trials of dietary advice. We identified 10 trials with a total of 1730 participants randomised, and one ongoing trial. Six trials investigated the provision of fruit and vegetables, and four trials examined advice to increase fruit and vegetable consumption.The ongoing trial is examining the provision of an avocado-rich diet.The number and type of intervention components for provision, and the dietary advice provided differed between trials.None of the trials reported clinical events as they were all relatively short term. There was no strong evidence for effects of individual trials of provision of fruit and vegetables on cardiovascular risk factors, but trials were heterogeneous and short term. Furthermore, five of the six trials only provided one fruit or vegetable. Dietary advice showed some favourable effects on blood pressure (systolic blood pressure (SBP): mean difference (MD) -3.0 mmHg (95% confidence interval (CI) -4.92 to -1.09), diastolic blood pressure (DBP): MD -0.90 mmHg (95% CI -2.03 to 0.24)) and low-density lipoprotein (LDL) cholesterol but analyses were based on only two trials. Three of the 10 included trials examined adverse effects, which included increased bowel movements, bad breath and body odour. There are very few studies to date examining provision of, or advice to increase the consumption of, fruit and vegetables in the absence of additional dietary interventions or other lifestyle interventions for the primary prevention of CVD. The limited evidence suggests advice to increase fruit and vegetables as a single intervention has favourable effects on CVD risk factors but more trials are needed to confirm this.

Systematic Reviews Published in Emergency Medicine Journals Do Not Routinely Search Clinical Trials Registries: A Cross-Sectional Analysis.

PubMed

Keil, Lukas G; Platts-Mills, Timothy F; Jones, Christopher W

2015-10-01

Publication bias compromises the validity of systematic reviews. This problem can be addressed in part through searching clinical trials registries to identify unpublished studies. This study aims to determine how often systematic reviews published in emergency medicine journals include clinical trials registry searches. We identified all systematic reviews published in the 6 highest-impact emergency medicine journals between January 1 and December 31, 2013. Systematic reviews that assessed the effects of an intervention were further examined to determine whether the authors described searching a clinical trials registry and whether this search identified relevant unpublished studies. Of 191 articles identified through PubMed search, 80 were confirmed to be systematic reviews. Our sample consisted of 41 systematic reviews that assessed a specific intervention. Eight of these 41 (20%) searched a clinical trials registry. For 4 of these 8 reviews, the registry search identified at least 1 relevant unpublished study. Systematic reviews published in emergency medicine journals do not routinely include searches of clinical trials registries. By helping authors identify unpublished trial data, the addition of registry searches may improve the validity of systematic reviews. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Systematic review of the diagnosis of scabies in therapeutic trials.

PubMed

Thompson, M J; Engelman, D; Gholam, K; Fuller, L C; Steer, A C

2017-07-01

Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies. © 2017 British Association of Dermatologists.

Getting inside acupuncture trials - Exploring intervention theory and rationale

PubMed Central

2011-01-01

Background Acupuncture can be described as a complex intervention. In reports of clinical trials the mechanism of acupuncture (that is, the process by which change is effected) is often left unstated or not known. This is problematic in assisting understanding of how acupuncture might work and in drawing together evidence on the potential benefits of acupuncture. Our aim was to aid the identification of the assumed mechanisms underlying the acupuncture interventions in clinical trials by developing an analytical framework to differentiate two contrasting approaches to acupuncture (traditional acupuncture and Western medical acupuncture). Methods Based on the principles of realist review, an analytical framework to differentiate these two contrasting approaches was developed. In order to see how useful the framework was in uncovering the theoretical rationale, it was applied to a set of trials of acupuncture for fatigue and vasomotor symptoms, identified from a wider literature review of acupuncture and early stage breast cancer. Results When examined for the degree to which a study demonstrated adherence to a theoretical model, two of the fourteen selected studies could be considered TA, five MA, with the remaining seven not fitting into any recognisable model. When examined by symptom, five of the nine vasomotor studies, all from one group of researchers, are arguably in the MA category, and two a TA model; in contrast, none of the five fatigue studies could be classed as either MA or TA and all studies had a weak rationale for the chosen treatment for fatigue. Conclusion Our application of the framework to the selected studies suggests that it is a useful tool to help uncover the therapeutic rationale of acupuncture interventions in clinical trials, for distinguishing between TA and MA approaches and for exploring issues of model validity. English language acupuncture trials frequently fail to report enough detail relating to the intervention. We advocate using this framework to aid reporting, along with further testing and refinement of the framework. PMID:21414187

Contextual control over selective attention: evidence from a two-target method.

PubMed

MacLellan, Ellen; Shore, David I; Milliken, Bruce

2015-07-01

Selective attention is generally studied with conflict tasks, using response time as the dependent measure. Here, we study the impact of selective attention to a first target, T1, presented simultaneously with a distractor, on the accuracy of subsequent encoding of a second target item, T2. This procedure produces an "attentional blink" (AB) effect much like that reported in other studies, and allowed us to study the influence of context on cognitive control with a novel method. In particular, we examined whether preparation to attend selectively to T1 had an impact on the selective encoding of T1 that would translate to report of T2. Preparation to attend selectively was manipulated by varying whether difficult selective attention T1 trials were presented in the context of other difficult selective attention T1 trials. The results revealed strong context effects of this nature, with smaller AB effects when difficult selective attention T1 trials were embedded in a context with many, rather than few, other difficult selective attention T1 trials. Further, the results suggest that both the trial-to-trial local context and the block-wide global context modulate performance in this task.

Memory systems in the rat: effects of reward probability, context, and congruency between working and reference memory.

PubMed

Roberts, William A; Guitar, Nicole A; Marsh, Heidi L; MacDonald, Hayden

2016-05-01

The interaction of working and reference memory was studied in rats on an eight-arm radial maze. In two experiments, rats were trained to perform working memory and reference memory tasks. On working memory trials, they were allowed to enter four randomly chosen arms for reward in a study phase and then had to choose the unentered arms for reward in a test phase. On reference memory trials, they had to learn to visit the same four arms on the maze on every trial for reward. Retention was tested on working memory trials in which the interval between the study and test phase was 15 s, 15 min, or 30 min. At each retention interval, tests were performed in which the correct WM arms were either congruent or incongruent with the correct RM arms. Both experiments showed that congruency interacted with retention interval, yielding more forgetting at 30 min on incongruent trials than on congruent trials. The effect of reference memory strength on the congruency effect was examined in Experiment 1, and the effect of associating different contexts with working and reference memory on the congruency effect was studied in Experiment 2.

The role of ECT in posttraumatic stress disorder: A systematic review.

PubMed

Youssef, Nagy A; McCall, W Vaughn; Andrade, Chittaranjan

2017-02-01

Posttraumatic stress disorder (PTSD) is associated with a high burden of disability and mortality and frequently is treatment resistant. There is little to offer patients who are not responding to standard interventions. Thus, the objective of this report is to systematically review human data on whether electroconvulsive therapy (ECT) is effective in PTSD. We performed a systematic literature review from 1958 through August 2016 for clinical studies and case reports published in English examining the efficacy of ECT in improving PTSD symptoms. The literature search generated 3 retrospective studies, 1 prospective uncontrolled clinical trial, and 5 case reports. It is not clear, given the small sample size and lack of a large randomized trial, whether favorable outcomes were attributed to improvement in depression (as opposed to core PTSD symptoms). Current efficacy data do not separate conclusively the effects of ECT on PTSD symptoms from those on depression. Randomized controlled trials are necessary to examine the use of ECT in medication-refractory PTSD patients with and without comorbid depression. Subsequent studies may address response in PTSD subtypes, and the use of novel techniques, such as memory reactivation, before ECT.

Quality of Reporting Nutritional Randomized Controlled Trials in Patients With Cystic Fibrosis.

PubMed

Daitch, Vered; Babich, Tanya; Singer, Pierre; Leibovici, Leonard

2016-08-01

Randomized controlled trials (RCTs) have a major role in the making of evidence-based guidelines. The aim of the present study was to critically appraise the RCTs that addressed nutritional interventions in patients with cystic fibrosis. Embase, PubMed, and the Cochrane Library were systematically searched until July 2015. Methodology and reporting of nutritional RCTs were evaluated by the Consolidated Standards of Reporting Trials (CONSORT) checklist and additional dimensions relevant to patients with CF. Fifty-one RCTs were included. Full details on methods were provided in a minority of studies. The mean duration of intervention was <6 months. 56.9% of the RCTs did not define a primary outcome; 70.6% of studies did not provide details on sample size calculation; and only 31.4% reported on the subgroup or separated between important subgroups. The examined RCTs were characterized by a weak methodology, a small number of patients with no sample size calculations, a relatively short intervention, and many times did not examine the outcomes that are important to the patient. Improvement over the years has been minor.

The ethics of sham surgery on research subjects with cognitive impairments that affect decision-making capacity.

PubMed

Resnik, David B; Miller, Frank

2010-09-01

Populations recruited to participate in sham surgery clinical trials sometimes include patients with cognitive impairments that affect decision-making capacity. In this commentary we examine arguments for and against including these patients in sham surgery clinical trials. We argue that patients with cognitive impairments that affect decision-making capacity should not be excluded from a sham surgery clinical trial if there are scientific reasons for including them in the study and basic ethical requirements for clinical research are met. Published by Elsevier Inc.

In “Step” with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study

PubMed Central

Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373

A randomized controlled Alzheimer's disease prevention trial's evolution into an exposure trial: the PREADViSE Trial.

PubMed

Kryscio, R J; Abner, E L; Schmitt, F A; Goodman, P J; Mendiondo, M; Caban-Holt, A; Dennis, B C; Mathews, M; Klein, E A; Crowley, J J

2013-01-01

To summarize the ongoing prevention of Alzheimer's disease (AD) by vitamin E and selenium (PREADViSE) trial as an ancillary study to SELECT (a large prostate cancer prevention trial) and to present the blinded results of the first year as an exposure study. PREADViSE was designed as a double blind randomized controlled trial (RCT). SELECT terminated after median of 5.5 years of exposure to supplements due to a futility analysis. Both trials then converted into an exposure study. In the randomized component PREADViSE enrolled 7,547 men age 62 or older (60 if African American). Once the trial terminated 4,246 of these men volunteered for the exposure study. Demographics were similar for both groups with exposure volunteers having baseline mean age 67.3 ± 5.2 years, 15.3 ± 2.4 years of education, 9.8% African Americans, and 22.0% reporting a family history of dementia. In the RCT men were randomly assigned to either daily doses of 400 IU of vitamin E or placebo and 200 µg of selenium or placebo using a 2x2 factorial structure. In the RCT, participants completed the memory impairment screen (MIS), and if they failed, underwent a longer screening (based on an expanded Consortium to Establish a Registry in AD [CERAD] battery). CERAD failure resulted in visits to their clinician for medical examination with records of these examinations forwarded to the PREADViSE center for further review. In the exposure study, men are contacted by telephone and complete the telephone version of the memory impairment screen (MIS-T) screen. If they fail the MIS-T, a modified telephone interview of cognitive status (TICS-M) exam is given. A failed TICS-M exam also leads to a visit to their clinician for an in-depth examination and forwarding of records for a centralized consensus diagnosis by expert clinicians. A subgroup of the men who pass the MIS-T also take the TICS-M exam for validation purposes. While this ancillary trial was open to all 427 SELECT clinical sites, only 130 (30.0%) of the sites chose to participate in PREADViSE. Staff turnover at the sites presented challenges when training persons unfamiliar with cognitive testing procedures to conduct the memory screens. In the RCT few participants (1.6%) failed the MIS screen and among those who passed this screen a significant practice effect was encountered. In the exposure study 3,581 men were reached by phone in year 1, 15.7% could not be reached after 5 calls, and of those contacted 6.0% refused the screen even after consenting to the procedures at their clinical site. Most notable is that the failure rate for the MIS-T increased fourfold to 7.2%. Of the 257 men who took the TICS-M, 84.0% failed and were asked to contact their physicians for a more detailed memory assessment, and approximately half of these had some form of dementia or cognitive impairment. Several of these dementia cases are not AD. Partnering with SELECT led to an AD prevention trial conducted at a very reasonable cost by taking advantage of the experience and efficient clinical trial management found in a cancer cooperative group (Southwest Oncology Group or SWOG). Once unblinded, the RCT and exposure study data have the potential to yield new information on long term exposure to antioxidant supplements under controlled conditions.

The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review.

PubMed

Wahabi, H A; Alansary, L A; Al-Sabban, A H; Glasziuo, P

2010-02-01

Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.

Examining Teachers' Attitudes and Experiences with Coaching to Inform Research-Based Practice: An Iterative Developmental Design Study

ERIC Educational Resources Information Center

Shernoff, Elisa S.; Lekwa, Adam J.; Reddy, Linda A.; Coccaro, Candace

2017-01-01

The purpose of this qualitative study was to examine teachers' attitudes and experiences with coaching. This study was conducted in advance of a planned randomized controlled trial of a coaching intervention to better align the model with teachers' needs and goals. Thirty-four K-5 general (n = 26), special education (n = 6), and educational…

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

PubMed

Sugawara, Norio; Ishioka, Masamichi; Tsuchimine, Shoko; Tsuruga, Koji; Sato, Yasushi; Tarakita, Natsumi; Furukori, Hanako; Kudo, Shuhei; Tomita, Tetsu; Nakagami, Taku; Yasui-Furukori, Norio

2018-01-01

Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. Patients were asked about possible participation in placebo-controlled clinical trials. Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial. Copyright © 2017. Published by Elsevier B.V.

The effects of gum chewing while walking on physical and physiological functions.

PubMed

Hamada, Yuka; Yanaoka, Takuma; Kashiwabara, Kyoko; Kurata, Kuran; Yamamoto, Ryo; Kanno, Susumu; Ando, Tomonori; Miyashita, Masashi

2018-04-01

[Purpose] This study examined the effects of gum chewing while walking on physical and physiological functions. [Subjects and Methods] This study enrolled 46 male and female participants aged 21-69 years. In the experimental trial, participants walked at natural paces for 15 minutes while chewing two gum pellets after a 1-hour rest period. In the control trial, participants walked at natural paces for 15 minutes after ingesting powder containing the same ingredient, except the gum base, as the chewing gum. Heart rates, walking distances, walking speeds, steps, and energy expenditure were measured. [Results] Heart rates during walking and heart rate changes (i.e., from at rest to during walking) significantly increased during the gum trial compared with the control trial. Walking distance, walking speed, walking heart rate, and heart rate changes in male participants and walking heart rate and heart rate changes in female participants were significantly higher during the gum trial than the control trial. In middle-aged and elderly male participants aged ≥40 years, walking distance, walking speed, steps, and energy expenditure significantly increased during the gum trial than the control trial. [Conclusion] Gum chewing while walking measurably affects physical and physiological functions.

The effects of gum chewing while walking on physical and physiological functions

PubMed Central

Hamada, Yuka; Yanaoka, Takuma; Kashiwabara, Kyoko; Kurata, Kuran; Yamamoto, Ryo; Kanno, Susumu; Ando, Tomonori; Miyashita, Masashi

2018-01-01

[Purpose] This study examined the effects of gum chewing while walking on physical and physiological functions. [Subjects and Methods] This study enrolled 46 male and female participants aged 21–69 years. In the experimental trial, participants walked at natural paces for 15 minutes while chewing two gum pellets after a 1-hour rest period. In the control trial, participants walked at natural paces for 15 minutes after ingesting powder containing the same ingredient, except the gum base, as the chewing gum. Heart rates, walking distances, walking speeds, steps, and energy expenditure were measured. [Results] Heart rates during walking and heart rate changes (i.e., from at rest to during walking) significantly increased during the gum trial compared with the control trial. Walking distance, walking speed, walking heart rate, and heart rate changes in male participants and walking heart rate and heart rate changes in female participants were significantly higher during the gum trial than the control trial. In middle-aged and elderly male participants aged ≥40 years, walking distance, walking speed, steps, and energy expenditure significantly increased during the gum trial than the control trial. [Conclusion] Gum chewing while walking measurably affects physical and physiological functions. PMID:29706720

F157. HIERARCHICAL PREDICTION ERRORS DURING AUDITORY MISMATCH UNDER PHARMACOLOGICAL MANIPULATIONS: A COMPUTATIONAL SINGLE-TRIAL EEG ANALYSIS

PubMed Central

Weber, Lilian; Diaconescu, Andreea; Tomiello, Sara; Schöbi, Dario; Iglesias, Sandra; Mathys, Christoph; Haker, Helene; Stefanics, Gabor; Schmidt, André; Kometer, Michael; Vollenweider, Franz X; Stephan, Klaas Enno

2018-01-01

Abstract Background A central theme of contemporary neuroscience is the notion that the brain embodies a generative model of its sensory inputs to infer on the underlying environmental causes, and that it uses hierarchical prediction errors (PEs) to continuously update this model. In two pharmacological EEG studies, we investigate trial-wise hierarchical PEs during the auditory mismatch negativity (MMN), an electrophysiological response to unexpected events, which depends on NMDA-receptor mediated plasticity and has repeatedly been shown to be reduced in schizophrenia. Methods Study1: Reanalysis of 64 channel EEG data from a previously published MMN study (Schmidt et al., 2012) using a placebo-controlled, within-subject design (N=19) to examine the effect of S-ketamine. Study2: 64 channel EEG data recorded during MMN (between subjects, double-blind, placebo-controlled design, N=73), to examine the effects of amisulpride and biperiden. Using the Hierarchical Gaussian Filter, a Bayesian learning model, we extracted trial-by-trial PE estimates on two hierarchical levels. These served as regressors in a GLM of trial-wise EEG signals at the sensor level. Results We find strong correlations of EEG with both PEs in both samples: lower-level PEs show effects early on (Study1: 133ms post-stimulus, Study2: 177ms), higher-level PEs later (Study1: 240ms, Study2: 450ms). The temporal order of these signatures thus mimics the hierarchical relationship of the PEs, as proposed by our computational model, where lower level beliefs need to be updated before learning can ensue on higher levels. Ketamine significantly reduced the representation of the higher-level PE in Study1. (Study2 has not been unblinded.) Discussion These studies present first evidence for hierarchical PEs during MMN and demonstrate that single-trial analyses guided by a computational model can distinguish different types (levels) of PEs, which are differentially linked to neuromodulators of demonstrated relevance for schizophrenia. Our analysis approach thus provides better mechanistic interpretability of pharmacological MMN studies, which will hopefully support the development of computational assays for diagnosis and treatment predictions in schizophrenia.

Can Lifestyle Modification Improve Neurocognition? Rationale and Design of the ENLIGHTEN Clinical Trial

PubMed Central

Blumenthal, James A.; Smith, Patrick J.; Welsh-Bohmer, Kathleen; Babyak, Michael A.; Browndyke, Jeffrey; Lin, Pao-Hwa; Doraiswamy, P. Murali; Burke, James; Kraus, William; Hinderliter, Alan; Sherwood, Andrew

2013-01-01

Background Risk factors for cardiovascular disease (CVD) not only increase the risk for clinical CVD events, but also are associated with a cascade of neurophysiologic and neuroanatomic changes that increase the risk of cognitive impairment and dementia. Although epidemiological studies have shown that exercise and diet are associated with lower CVD risk and reduced incidence of dementia, no randomized controlled trial (RCT) has examined the independent effects of exercise and diet on neurocognitive function among individuals at risk for dementia. The ENLIGHTEN trial is a RCT of patients with CVD risk factors who also are characterized by subjective cognitive complaints and objective evidence of neurocognitive impairment without dementia (CIND) Study Design A 2 by 2 design will examine the independent and combined effects of diet and exercise on neurocognition. 160 participants diagnosed with CIND will be randomly assigned to 6 months of aerobic exercise, the DASH diet, or a combination of both exercise and diet; a (control) group will receive health education but otherwise will maintain their usual dietary and activity habits. Participants will complete comprehensive assessments of neurocognitive functioning along with biomarkers of CVD risk including measures of blood pressure, glucose, endothelial function, and arterial stiffness. Conclusion The ENLIGHTEN trial will (a) evaluate the effectiveness of aerobic exercise and the DASH diet in improving neurocognitive functioning in CIND patients with CVD risk factors; (b) examine possible mechanisms by which exercise and diet improve neurocognition; and (c) consider potential moderators of treatment, including subclinical CVD. PMID:23000080

The quality of the reported sample size calculations in randomized controlled trials indexed in PubMed.

PubMed

Lee, Paul H; Tse, Andy C Y

2017-05-01

There are limited data on the quality of reporting of information essential for replication of the calculation as well as the accuracy of the sample size calculation. We examine the current quality of reporting of the sample size calculation in randomized controlled trials (RCTs) published in PubMed and to examine the variation in reporting across study design, study characteristics, and journal impact factor. We also reviewed the targeted sample size reported in trial registries. We reviewed and analyzed all RCTs published in December 2014 with journals indexed in PubMed. The 2014 Impact Factors for the journals were used as proxies for their quality. Of the 451 analyzed papers, 58.1% reported an a priori sample size calculation. Nearly all papers provided the level of significance (97.7%) and desired power (96.6%), and most of the papers reported the minimum clinically important effect size (73.3%). The median (inter-quartile range) of the percentage difference of the reported and calculated sample size calculation was 0.0% (IQR -4.6%;3.0%). The accuracy of the reported sample size was better for studies published in journals that endorsed the CONSORT statement and journals with an impact factor. A total of 98 papers had provided targeted sample size on trial registries and about two-third of these papers (n=62) reported sample size calculation, but only 25 (40.3%) had no discrepancy with the reported number in the trial registries. The reporting of the sample size calculation in RCTs published in PubMed-indexed journals and trial registries were poor. The CONSORT statement should be more widely endorsed. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Motivators of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies.

PubMed

Dhalla, Shayesta; Poole, Gary

2011-11-01

HIV vaccine preparedness studies (VPS) are important precursors to HIV vaccine trials. As well, they contribute to an understanding of motivators and barriers for participation in hypothetical HIV vaccine trials. Motivators can take the form of altruism and a desire for social benefits. Perceived personal benefits, including psychological, personal, and financial well-being, may also motivate participation. The authors performed a systematic review of HIV VPS using the Cochrane Database for Systematic Reviews, Medline, PubMed, Embase, and Google Scholar. The authors independently searched the literature for individual HIV VPS that examined motivators of participation in a hypothetical HIV vaccine trial, using the same search strategy. As the denominators employed in the literature varied across studies, the denominators were standardized to the number of respondents per survey item, regardless of their willingness to participate (WTP) in an HIV vaccine trial. The authors retrieved eight studies on social benefits (i.e., altruism) and 11 studies on personal benefits conducted in the Organization for Economic Co-operation and Development (OECD) countries, as well as 19 studies on social benefits and 20 studies on personal benefits in the non-OECD countries. Various different forms of altruism were found to be the major motivators for participation in an HIV vaccine trial in both the OECD and the non-OECD countries. In a large number of studies, protection from HIV was cited as a personal motivator for participation in a hypothetical HIV vaccine trial in the OECD and the non-OECD countries. Knowledge of motivators can inform and target recruitment for HIV vaccine trials, although it must be remembered that hypothetical motivators may not always translate into motivators in an actual vaccine trial.

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.

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.

Funding oncology clinical trials: are cooperative group trials sustainable?

PubMed

Seow, Hsien-Yeang; Whelan, Patrick; Levine, Mark N; Cowan, Kathryn; Lysakowski, Barbara; Kowaleski, Brenda; Snider, Anne; Xu, Rebecca Y; Arnold, Andrew

2012-05-01

Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.

Do quality improvement initiatives for diabetes care address social inequities? Secondary analysis of a systematic review.

PubMed

Lu, Jacquie Boyang; Danko, Kristin J; Elfassy, Michael D; Welch, Vivian; Grimshaw, Jeremy M; Ivers, Noah M

2018-02-14

Socially disadvantaged populations carry a disproportionate burden of diabetes-related morbidity and mortality. There is an emerging interest in quality improvement (QI) strategies in the care of patients with diabetes, however, the effect of these interventions on disadvantaged groups remains unclear. This is a secondary analysis of a systematic review that seeks to examine the extent of equity considerations in diabetes QI studies, specifically quantifying the proportion of studies that target interventions toward disadvantaged populations and conduct analyses on the impact of interventions on disadvantaged groups. Studies were identified using Medline, HealthStar and the Cochrane Effective Practice and Organisation of Care database. Randomised controlled trials assessing 12 QI strategies targeting health systems, healthcare professionals and/or patients for the management of adult outpatients with diabetes were eligible. The place of residence, race/ethnicity/culture/language, occupational status, gender/sexual identity, religious affiliations, education level, socioeconomic status, social capital, plus age, disability, sexual preferences and relationships (PROGRESS-Plus) framework was used to identify trials that focused on disadvantaged patient populations, to examine the types of equity-relevant factors that are being considered and to explore temporal trends in equity-relevant diabetes QI trials. Of the 278 trials that met the inclusion criteria, 95 trials had equity-relevant considerations. These include 64 targeted trials that focused on a disadvantaged population with the aim to improve the health status of that population and 31 general trials that undertook subgroup analyses to assess the extent to which their interventions may have had differential impacts on disadvantaged subgroups. Trials predominantly focused on race/ethnicity, socioeconomic status and place of residence as potential factors for disadvantage in patients receiving diabetes care. Less than one-third of diabetes QI trials included equity-relevant considerations, limiting the relevance and applicability of their data to disadvantaged populations. There is a need for better data collection, reporting, analysis and interventions on the social determinants of health that may influence the health outcomes of patients with diabetes. CRD42013005165. © 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.

Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.

PubMed

Khan, Arif; Kolts, Russell L; Thase, Michael E; Krishnan, K Ranga Rama; Brown, Walter

2004-11-01

The authors examined which, if any, research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials. Clinical trial data were reviewed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000. From the antidepressant research programs on these medications, 52 clinical trials were included in the study. The authors evaluated trial design features, patient characteristics, and difference in response between placebo and antidepressant. Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants. The severity of depressive symptoms before patient randomization, the dosing schedule (flexible versus fixed), the number of treatment arms, and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo. The duration of the antidepressant trial, number of patients per treatment arm, number of sites, and mean age of the patients were similar in successful trials (with a greater antidepressant-placebo difference) and less successful trials (with a smaller antidepressant-placebo difference). These findings may help in the design of future antidepressant trials.

The effect of whole body vibration on balance, gait performance and mobility in people with stroke: a systematic review and meta-analysis.

PubMed

Yang, Xiaotian; Wang, Pu; Liu, Chuan; He, Chengqi; Reinhardt, Jan D

2015-07-01

To examine the effect of whole body vibration on balance, gait performance and mobility among people with stroke. A systematic review was conducted by two independent reviewers who completed the article search and selection. We included randomized controlled trials published in English examining effects of whole body vibration on balance, gait, mobility, muscle strength and muscle tone in adults with a clinical diagnosis of stroke. Articles were excluded if they were research studies on people with other primary diagnosis, abstracts published in the conferences or books. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies. Sources included Cochrane Central Register of Controlled Trials, Pubmed, MEDLINE, CINAHL, EMBASE, PEDro, PsycINFO, Science Citation Index, ClinicalTrials.gov, Current Controlled Trials, Stroke Trials Registry, and reference lists of all relevant articles. Eight randomized controlled trials (nine articles) involving 271 participants were included in this meta-analysis. No significant improvement was found regarding Berg balance scale (SMD=-0.08, 95%CI=-1.35 to 1.19, P=0.91), mobility (SMD=0.45, 95%CI=-0.46 to 1.37, P=0.33), maximal isometric contracion of knee extension strength (SMD=0.23, 95%CI=-0.27 to 0.74, P=0.36), and maximal isometric contracion of knee extension strength (SMD=0.09, 95%CI=-0.38 to 0.56, P=0.71). There was no evidence for effects of whole body vibration on balance in people with stroke. Effects of whole body vibration on mobility and gait performance remain inconclusive. More large and high-quality trials are required. © The Author(s) 2014.

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

PubMed Central

Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2009-01-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

Dietary Flavonoids and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

PubMed Central

Bobe, Gerd; Sansbury, Leah B.; Albert, Paul S.; Cross, Amanda J.; Kahle, Lisa; Ashby, Jason; Slattery, Martha L.; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Marshall, James R.; Schatzkin, Arthur; Lanza, Elaine

2008-01-01

Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non–steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; Ptrend = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. PMID:18559549

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

PubMed

Fair, Damien A; Choi, Alexander H; Dosenbach, Yannic B L; Coalson, Rebecca S; Miezin, Francis M; Petersen, Steven E; Schlaggar, Bradley L

2010-08-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. 2009 Elsevier Inc. All rights reserved.

Younger and Older Adults Weigh Multiple Cues in a Similar Manner to Generate Judgments of Learning

PubMed Central

Hines, Jarrod C.; Hertzog, Christopher; Touron, Dayna R.

2015-01-01

One's memory for past test performance (MPT) is a key piece of information individuals use when deciding how to restudy material. We used a multi-trial recognition memory task to examine adult age differences in the influence of MPT (measured by actual Trial 1 memory accuracy and subjective confidence judgments, CJs) along with Trial 1 judgments of learning (JOLs), objective and participant-estimated recognition fluencies, and Trial 2 study time on Trial 2 JOLs. We found evidence of simultaneous and independent influences of multiple objective and subjective (i.e., metacognitive) cues on Trial 2 JOLs, and these relationships were highly similar for younger and older adults. Individual differences in Trial 1 recognition accuracy and CJs on Trial 2 JOLs indicate that individuals may vary in the degree to which they rely on each MPT cue when assessing subsequent memory confidence. Aging appears to spare the ability to access multiple cues when making JOLs. PMID:25827630

Motivators to participation in actual HIV vaccine trials.

PubMed

Dhalla, Shayesta; Poole, Gary

2014-02-01

An examination of actual HIV vaccine trials can contribute to an understanding of motivators for participation in these studies. Analysis of these motivators reveals that they can be categorized as social and personal benefits. Social benefits are generally altruistic, whereas personal benefits are psychological, physical, and financial. In this systematic review, the authors performed a literature search for actual preventive HIV vaccine trials reporting motivators to participation. Of studies conducted in the Organization for Economic Co-operation and Development (OECD) countries, the authors retrieved 12 studies reporting on social benefits and seven reporting on personal benefits. From the non-OECD countries, nine studies reported on social benefits and eight studies on personal benefits. Social benefits were most frequently described on macroscopic, altruistic levels. Personal benefits were most frequently psychological in nature. Rates of participation were compared between the OECD and the non-OECD countries. Knowledge of actual motivators in specific countries and regions can help target recruitment in various types of actual HIV vaccine trials.

Water-saving impacts of Smart Meter technology: An empirical 5 year, whole-of-community study in Sydney, Australia

NASA Astrophysics Data System (ADS)

Davies, Kirsten; Doolan, Corinna; van den Honert, Robin; Shi, Rose

2014-09-01

In 2009-2010 Sydney Water, the primary water utility in Sydney, conducted a comprehensive Smart Metering trial in residential homes in the suburb of Westleigh, in Sydney's north. The trial involved 1923 participants residing in 630 households. A whole-of-community method of engagement was applied to capture the views of residents from 12 to 70+ years of age. The trial examined the effects of the technology on the water consumption of an intervention group compared with that of a matched control group. After removing properties that had been sold since the beginning of the trial, properties in the study group were matched with a control group property on the basis of the household size, property size and the presence (or otherwise) of a swimming pool. The effects of the technology on consumption were measured and analyzed for the period July 2009 to June 2010, coupled with qualitative information that was collected throughout the duration of the study. A key finding was that households with the in-home display (IHD) installed, reduced their consumption by an average of over 6.8% over the study period when compared to the control group. Since completion of the study the community has not had any further interventions. The trial created an opportunity to examine the longer-term effects of the technology (June 2008 to September 2013). Consumption data collected over the 3 year posttrial period revealed that the participant group consumed 6.4% per month less water when compared to the pretrial period, whilst the matched control group consumed 1.3% per month more water when compared to the pretrial period. The reduced consumption of the participant group was maintained over time, demonstrating the long-term value of this technology.

Unfractionated or low-molecular weight heparin for induction of remission in ulcerative colitis.

PubMed

Chande, N; McDonald, J W; Macdonald, J K

2008-04-16

There are a limited number of treatment options for patients with ulcerative colitis (UC). An increased risk of thrombosis in UC coupled with an observation that UC patients being treated with anticoagulant therapy for thrombotic events had an improvement in their bowel symptoms led to trials examining the use of unfractionated heparin (UFH) and low molecular weight heparins (LMWH) in patients with active UC. To review randomized trials examining the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis. The MEDLINE (PUBMED), and EMBASE databases, The Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD group specialized trials register, review papers on ulcerative colitis, and references from identified papers were searched in an effort to identify all randomized trials studying UFH or LMWH use in patients with ulcerative colitis. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. Each author independently reviewed potentially relevant trials to determine their eligibility for inclusion based on the criteria identified above. The Jadad scale was used to assess study quality. Studies published in abstract form only were included if the authors could be contacted for further information. A data extraction form was developed and used to extract data from included studies. At least 2 authors independently extracted data. Any disagreements were resolved by consensus. Data were analyzed using Review Manager (RevMan 4.2.9). Data were analyzed on an intention-to-treat basis, and treated dichotomously. In cross-over studies, only data from the first arm were included. The primary endpoint was induction of remission, as defined by the studies. Data were combined for analysis if they assessed the same treatments (UFH or LMWH versus placebo or other therapy). If a comparison was only assessed in a single trial, P-values were derived using the chi-square test. If the comparison was assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals (95% CI). The presence of heterogeneity among studies was assessed using the chi-square test (a P value of 0.10 was regarded as statistically significant). If statistically significant heterogeneity was identified the odds ratio and 95% CI were calculated using a random effects model. There were 2 randomized, double-blind studies assessing LMWH versus placebo for the treatment of mild-moderate active UC. Various outcomes were assessed in the 2 studies. LMWH showed no benefit over placebo in any outcome, including clinical remission (OR 1.09; 95% CI 0.26 to 4.63; P = 0.91), clinical improvement (OR 0.73; 95% CI 0.32 to 1.66; P = 0.45 and OR 1.09; 95% CI 0.18 to 6.58; P = 0.92 in the two studies, respectively), endoscopic improvement (OR 1.35; 95% CI 0.29 to 6.18; P = 0.70), or histological improvement (OR 2.00; 95% CI 0.45 to 8.96; P = 0.37). LMWH was also not beneficial when added to standard therapy in a randomized open-label trial in which the outcome measures included clinical remission (OR 0.71; 95% CI 0.17 to 2.95; P = 0.64), clinical improvement (OR 2.00; 95% CI 0.31 to 12.75; P = 0.46), endoscopic remission (OR 0.71; 95% CI 0.17 to 2.95; P = 0.64), or endoscopic improvement (OR 1.40; 95% CI 0.34 to 5.79; P = 0.64). LMWH was well-tolerated and provided no significant benefit for quality of life. One study examining UFH versus corticosteroids in the treatment of severe UC demonstrated inferiority of UFH in clinical improvement as an outcome measure (OR 0.02; 95% CI 0 to 0.40; P = 0.01). Patients assigned to UFH did not improve clinically. More patients assigned to UFH had rectal hemorrhage as an adverse event. There is no evidence to support the use of UFH or LMWH for the treatment of active UC. No further trials examining these drugs for patients with UC are warranted, except perhaps a trial of UFH in patients with mild disease. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.

Protocol for Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial: a randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services.

PubMed

Tickle, Martin; Milsom, Keith M; Donaldson, Michael; Killough, Seamus; O'Neill, Ciaran; Crealey, Grainne; Sutton, Matthew; Noble, Solveig; Greer, Margaret; Worthington, Helen V

2011-10-10

Dental caries is a persistent public health problem with little change in the prevalence in young children over the last 20 years. Once a child contracts the disease it has a significant impact on their quality of life. There is good evidence from Cochrane reviews including trials that fluoride varnish and regular use of fluoride toothpaste can prevent caries. The Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial will compare the costs and effects of a caries preventive package (fluoride varnish, toothpaste, toothbrush and standardised dental health education) with dental health education alone in young children. A randomised controlled trial on children initially aged 2 and 3 years old who are regular attenders at the primary dental care services in Northern Ireland. Children will be recruited and randomised in dental practices. Children will be randomised to the prevention package of both fluoride varnish (twice per year for three years), fluoride toothpaste (1,450 ppm F) (supplied twice per year), a toothbrush (supplied twice a year) or not; both test and control groups receive standardised dental health education delivered by the dentist twice per year. Randomisation will be conducted by the Belfast Trust Clinical Research Support Centre ([CRSC] a Clinical Trials Unit). 1200 participants will be recruited from approximately 40 dental practices. Children will be examined for caries by independent dental examiners at baseline and will be excluded if they have caries. The independent dental examiners will examine the children again at 3 years blinded to study group.The primary end-point is whether the child develops caries (cavitation into dentine) or not over the three years. One secondary outcome is the number of carious surfaces in the primary dentition in children who experience caries. Other secondary outcomes are episodes of pain, extraction of primary teeth, other adverse events and costs which will be obtained from parental questionnaires. This is a pragmatic trial conducted in general dental practice. It tests a composite caries prevention intervention, which represents an evidence based approach advocated by current guidance from the English Department of Health which is feasible to deliver to all low risk (caries free) children in general dental practice. The trial will provide valuable information to policy makers and clinicians on the costs and effects of caries prevention delivered to young children in general dental practice. EudraCT No: 2009 - 010725 - 39 ISRCTN: ISRCTN36180119 Ethics Reference No: 09/H1008/93:

Divalproex Sodium for the Treatment of PTSD and Conduct Disordered Youth: A Pilot Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki

2007-01-01

We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI)…

Treatment of Posttraumatic Stress Disorder by Trained Lay Counselors in an African Refugee Settlement: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Neuner, Frank; Onyut, Patience Lamaro; Ertl, Verena; Odenwald, Michael; Schauer, Elisabeth; Elbert, Thomas

2008-01-01

Traumatic stress due to conflict and war causes major mental health problems in many resource-poor countries. The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder (PTSD) in a refugee settlement. In a randomized controlled dissemination trial in Uganda with 277…

A Randomized Controlled Trial of a Home-Visiting Intervention Aimed at Preventing Relationship Problems in Depressed Mothers and Their Infants

ERIC Educational Resources Information Center

van Doesum, Karin T. M.; Riksen-Walraven, J. Marianne; Hosman, Clemens M. H.; Hoefnagels, Cees

2008-01-01

This study examined the effect of a mother-baby intervention on the quality of mother-child interaction, infant-mother attachment security, and infant socioemotional functioning in a group of depressed mothers with infants aged 1-12 months. A randomized controlled trial compared an experimental group (n = 35) receiving the intervention (8-10 home…

Measuring the Plasticity of Social Approach: A Randomized Controlled Trial of the Effects of the PEERS Intervention on EEG Asymmetry in Adolescents with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Van Hecke, Amy Vaughan; Stevens, Sheryl; Carson, Audrey M.; Karst, Jeffrey S.; Dolan, Bridget; Schohl, Kirsten; McKindles, Ryan J.; Remmel, Rheanna; Brockman, Scott

2015-01-01

This study examined whether the Program for the Education and Enrichment of Relational Skills ("PEERS: Social skills for teenagers with developmental and autism spectrum disorders: The PEERS treatment manual," Routledge, New York, 2010a) affected neural function, via EEG asymmetry, in a randomized controlled trial of adolescents with…

The Effectiveness of a Group Triple P with Chinese Parents Who Have a Child with Developmental Disabilities: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Fan, Angel; Sanders, Matthew R.

2013-01-01

The study examined the effectiveness of Group Triple P, a Level 4 variant of the Triple P multilevel system of parenting support, with Chinese parents who had a preschool aged child with a developmental disability, using randomized controlled trial design. Participants (Intervention group: 42; Waitlist Control group: 39) completed measures on…

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

PubMed

Moots, Robert J; Curiale, Cinzia; Petersel, Danielle; Rolland, Catherine; Jones, Heather; Mysler, Eduardo

2018-05-22

Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.

Clinical trial allocation in multinational pharmaceutical companies - a qualitative study on influential factors.

PubMed

Dombernowsky, Tilde; Haedersdal, Merete; Lassen, Ulrik; Thomsen, Simon F

2017-06-01

Clinical trial allocation in multinational pharmaceutical companies includes country selection and site selection. With emphasis on site selection, the overall aim of this study was to examine which factors pharmaceutical companies value most when allocating clinical trials. The specific aims were (1) to identify key decision makers during country and site selection, respectively, (2) to evaluate by which parameters subsidiaries are primarily assessed by headquarters with regard to conducting clinical trials, and (3) to evaluate which site-related qualities companies value most when selecting trial sites. Eleven semistructured interviews were conducted among employees engaged in trial allocation at 11 pharmaceutical companies. The interviews were analyzed by deductive content analysis, which included coding of data to a categorization matrix containing categories of site-related qualities. The results suggest that headquarters and regional departments are key decision makers during country selection, whereas subsidiaries decide on site selection. Study participants argued that headquarters primarily value timely patient recruitment and quality of data when assessing subsidiaries. The site-related qualities most commonly emphasized during interviews were study population availability, timely patient recruitment, resources at the site, and site personnel's interest and commitment. Costs of running the trials were described as less important. Site personnel experience in conducting trials was described as valuable but not imperative. In conclusion, multinational pharmaceutical companies consider recruitment-related factors as crucial when allocating clinical trials. Quality of data and site personnel's interest and commitment are also essential, whereas costs seem less important. While valued, site personnel experience in conducting clinical trials is not imperative.

Temporal Trends and Predictors for Cancer Clinical Trial Availability for Medically Underserved Populations

PubMed Central

Lakoduk, Ashley M.; Priddy, Laurin L.; Yan, Jingsheng; Xie, Xian-Jin

2015-01-01

Background. Lack of access to available cancer clinical trials has been cited as a key factor limiting trial accrual, particularly among medically underserved populations. We examined the trends and factors in clinical trial availability within a major U.S. safety-net hospital system. Materials and Methods. We identified cancer clinical trials activated at the Harold C. Simmons Cancer from 1991 to 2014 and recorded the characteristics of the trials that were and were not activated at the Parkland Health and Hospital System satellite site. We used univariate and multivariate logistic regression to determine the association between trial characteristics and nonactivation status, and chi-square analysis to determine the association between the trial characteristics and the reasons for nonactivation. Results. A total of 773 trials were identified, of which 152 (20%) were not activated at Parkland. In multivariable analysis, nonactivation at Parkland was associated with trial year, sponsor, and phase. Compared with the 1991–2006 period, clinical trials in the 2007–2014 period were almost eightfold more likely not to be activated at Parkland. The most common reasons for nonactivation at Parkland were an inability to perform the study procedures (27%) and the startup costs (15%). Conclusion. Over time, in this single-center setting, a decreasing proportion of cancer clinical trials were available to underserved populations. Trial complexity and costs appeared to account for much of this trend. Efforts to overcome these barriers will be key to equitable access to clinical trials, efficient accrual, and the generalizability of the results. Implications for Practice: Despite numerous calls to increase and diversify cancer clinical trial accrual, the present study found that cancer clinical trial activation rates in a safety-net setting for medically underserved populations have decreased substantially in recent years. The principal reasons for study nonactivation were expenses and an inability to perform the study-related procedures, reflecting the increasing costs and complexity of cancer clinical trials. Future efforts need to focus on strategies to mitigate the increasing disparity in access to clinical research and cutting-edge therapies, which also threatens to hinder study accrual, completion rates, and generalizability. PMID:26018661

Condylar position analysis with a new electronic condylar position measuring instrument E-CPM: influence of different examiners and a working bite on reproducibility.

PubMed

Vahle-Hinz, K; Rybczynski, A; Jakstat, H; Ahlers, M O

2009-01-01

Condylar position analysis facilitates a quantitative comparison of the condylar position with and without a bite record, different records and changed influencing factors. Handling by the examiner when positioning the model is a significant factor with regard to the accuracy of the examination. Measurement accuracy could be improved when positioning the models by using special working bites, hence the objective of the experiments described in this study consisted in examining the extent to which the measuring results are influenced by different examiners and by using working bites. In the first trial, one examiner performed ten measurements without and with an interposed working bite for five model pairs in each case. In the second trial, nine examiners (three specialized dentists, three dental assistants, three students) performed ten measurements in each case without and with an interposed working bite. The three-dimensional position was read digitally with the E-CPM (Gamma Dental, Klosterneuburg/Vienna, Austria), recorded by means of spreadsheet software (Microsoft Excel) and diagnostic software (CMDfact, CMD3D module, dentaConcept, Hamburg), and evaluated with graphing software (Sigma Plot, Systat Software, USA). In the first trial, it was shown that the reproducibility of mounting was improved markedly (p <0.01) by using bite records in the form of working bites. In the second trial, it was shown that the mean error increased significantly (p <0.01) when several examiners performed the measurements compared with the results of one examiner alone. No significantly different results occurred (p < 0.01) in the comparison of the different groups of examiners with different educational and training backgrounds. This applied for the mounting methods without and with working bite. On the other hand, the reproducibility of mounting improved distinctly (p<0.01) in every group of examiners when working bites were used. Reproducibility of condylar position analysis was improved significantly by mounting the models with special working bites. This applied for operators of different professional background (dentists, dental assistants and dental students), while there were no significant differences between results of the three groups.

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

Peyronie's disease intervention trials: methodological challenges and issues.

PubMed

Müller, Alexander; Mulhall, John P

2009-03-01

Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.

A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

Prevention Service System Transformation Using "Communities That Care"

ERIC Educational Resources Information Center

Brown, Eric C.; Hawkins, J. David; Arthur, Michael W.; Briney, John S.; Fagan, Abigail A.

2011-01-01

This study examines prevention system transformation as part of a community-randomized controlled trial of Communities That Care (CTC). Using data from surveys of community leaders, we examine differences between CTC and control communities 4.5 years after CTC implementation. Significantly higher levels of adopting a science-based approach to…

Predictors of web-based follow-up response in the Prevention of Low Back Pain in the Military Trial (POLM)

PubMed Central

2011-01-01

Background Achieving adequate follow-up in clinical trials is essential to establish the validity of the findings. Achieving adequate response rates reduces bias and increases probability that the findings can be generalized to the population of interest. Therefore, the purpose of this study was to determine the influence of attention, demographic, psychological, and health status factors on web-based response rates in the ongoing Prevention of Low Back Pain in the Military (POLM) trial. Methods Twenty companies of Soldiers (n = 4,325) were cluster randomized to complete a traditional exercise program including sit-ups (TEP) with or without a psychosocial educational program (PSEP) or a core stabilization exercise program (CSEP) with or without PSEP. A subgroup of Soldiers (n = 371) was randomized to receive an additional physical and ultrasound imaging (USI) examination of key trunk musculature. As part of the surveillance program, all Soldiers were encouraged to complete monthly surveys via email during the first year. Descriptive statistics of the predictor variables were obtained and compared between responders and non-responders using two sample t-tests or chi-square test, as appropriate. Generalized linear mixed models were subsequently fitted for the dichotomous outcomes to estimate the effects of the predictor variables. The significance level was set at .05 a priori. Results The overall response rate was 18.9% (811 subjects) for the first year. Responders were more likely to be older, Caucasian, have higher levels of education and income, reservist military status, non smoker, lower BMI, and have received individualized attention via the physical/USI examination (p < .05). Age, race/ethnicity, education, military status, smoking history, BMI, and whether a Soldier received the physical/USI examination remained statistically significant (p < .05) when considered in a full multivariate model. Conclusion The overall web based response rate during the first year of the POLM trial was consistent with studies that used similar methodology, but lower when compared to rates expected for standard clinical trials. One year response rate was significantly associated with demographic characteristics, health status, and individualized attention via additional testing. These data may assist for planning of future trials that use web based response systems. Trial Registration This study has been registered at reports at http://clinicaltrials.gov (NCT00373009). PMID:21668961

Treatment of substance use disorders in schizophrenia.

PubMed

Bennett, Melanie E; Bradshaw, Kristen R; Catalano, Lauren T

2017-07-01

Substance use disorders (SUDs) represent a great barrier to functional recovery for individuals with schizophrenia. It is important to use research on treatment of SUDs in schizophrenia to guide treatment recommendations and program planning. We review studies of pharmacological and psychosocial interventions to treat SUDs in individuals with schizophrenia. The criteria used to select studies for inclusion are (1) the percentage of the sample with a schizophrenia spectrum diagnosis is at least 25%; (2) participants have a comorbid SUD or problem use of substances; (3) an intervention for SUD is provided; (4) a substance use-related outcome is measured; and (5) the study design enabled examination of pre-post outcome measures including open label trials, nonrandomized evaluations (quasi-experimental designs, nonrandom assignment to groups), or randomized controlled trials. There are few psychopharmacology outcomes studies. Most have examined use of antipsychotic medications to treat SUDs in schizophrenia. Several trials have yielded positive findings for naltrexone in reducing drinking compared to placebo in this population. Motivational and cognitive-behavioral interventions are associated with decreased substance use in several trials. Treatment for SUDs is feasible within a range of settings and acceptable to many individuals with schizophrenia. All individuals with schizophrenia should be offered brief or more extended psychosocial interventions that incorporate discussion of personal reasons to change and training in cognitive-behavioral strategies to reduce use, cope with cravings and stress, and avoid relapse. Future research must include larger samples, longitudinal designs, and similar outcome measures across studies.

Comparing socially disadvantaged smokers who agree and decline to participate in a randomised smoking cessation trial

PubMed Central

Bonevski, Billie; Twyman, Laura; Paul, Chris; D'Este, Catherine; West, Robert; Siahpush, Mohammad; Oldmeadow, Christopher; Palazzi, Kerrin; Bryant, Jamie; Guillaumier, Ashleigh

2015-01-01

Objectives This study examined sociodemographic, smoking and psychosocial characteristics associated with consent to participate in a smoking cessation trial for socially disadvantaged smokers. Design Baseline data were collected prior to seeking consent for the Call it Quits, a randomised controlled trial. Setting An Australian social and community service organisation. Sociodemographic, smoking and psychosocial characteristics were compared between smokers who agreed or declined to participate. Participants Of the 584 smokers invited to participate, 431 (74%) consented and 153 (26%) declined. Results Logistic regression modelling indicates the ORs of participation were twice as high for those reporting ‘high’ motivation to quit compared to the ‘moderate’ motivation group, and five times higher than the ‘low’ motivation group (p=0.007). The ORs of consenting were higher for those with a preference for gradual reduction in cigarettes in quit attempts compared with ‘no preference’. The ORs were lower for those reporting ‘don't know’ regarding their enjoyment of smoking compared to ‘not at all’ enjoying smoking, and reporting that fewer of their family or friends smoked compared to ‘most or all’. Conclusions This study is the first to examine the characteristics of socially disadvantaged smokers who consent or decline to participate in a smoking cessation trial. Low-income smokers who are motivated to quit, are not enjoying smoking, had family or friends who smoked, and who are interested in gradual cessation approaches may be more likely to participate in a smoking cessation trial. Trial registration number ISRCTN85202510. PMID:26369799

Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials.

PubMed

de Labra, Carmen; Guimaraes-Pinheiro, Christyanne; Maseda, Ana; Lorenzo, Trinidad; Millán-Calenti, José C

2015-12-02

Low physical activity has been shown to be one of the most common components of frailty, and interventions have been considered to prevent or reverse this syndrome. The purpose of this systematic review of randomized, controlled trials is to examine the exercise interventions to manage frailty in older people. The PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched using specific keywords and Medical Subject Headings for randomized, controlled trials published during the period of 2003-2015, which enrolled frail older adults in an exercise intervention program. Studies where frailty had been defined were included in the review. A narrative synthesis approach was performed to examine the results. The Physiotherapy Evidence Database (PEDro scale) was used to assess the methodological quality of the selected studies. Of 507 articles, nine papers met the inclusion criteria. Of these, six included multi-component exercise interventions (aerobic and resistance training not coexisting in the intervention), one included physical comprehensive training, and two included exercises based on strength training. All nine of these trials included a control group receiving no treatment, maintaining their habitual lifestyle or using a home-based low level exercise program. Five investigated the effects of exercise on falls, and among them, three found a positive impact of exercise interventions on this parameter. Six trials reported the effects of exercise training on several aspects of mobility, and among them, four showed enhancements in several measurements of this outcome. Three trials focused on the effects of exercise intervention on balance performance, and one demonstrated enhanced balance. Four trials investigated functional ability, and two showed positive results after the intervention. Seven trials investigated the effects of exercise intervention on muscle strength, and five of them reported increases; three trials investigated the effects of exercise training on body composition, finding improvements in this parameter in two of them; finally, one trial investigated the effects of exercise on frailty using Fried's criteria and found an improvement in this measurement. Exercise interventions have demonstrated improvement in different outcome measurements in frail older adults, however, there were large differences between studies with regard to effect sizes. This systematic review suggested that frail older adults seemed to benefit from exercise interventions, although the optimal program remains unclear. More studies of this topic and with frail populations are needed to select the most favorable exercise program.

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

PubMed Central

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

2014-01-01

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

Comparing the Score Distribution of a Trial Computer-Based Examination Cohort with That of the Standard Paper-Based Examination Cohort

ERIC Educational Resources Information Center

Zoanetti, Nathan; Les, Magdalena; Leigh-Lancaster, David

2014-01-01

From 2011-2013 the VCAA conducted a trial aligning the use of computers in curriculum, pedagogy and assessment culminating in a group of 62 volunteer students sitting their end of Year 12 technology-active Mathematical Methods (CAS) Examination 2 as a computer-based examination. This paper reports on statistical modelling undertaken to compare the…

Trait-based cue Utilization and initial skill acquisition: implications for models of the progression to expertise

PubMed Central

Wiggins, Mark W.; Brouwers, Sue; Davies, Joel; Loveday, Thomas

2014-01-01

The primary aim of this study was to examine the role of cue utilization in the initial acquisition of psycho-motor skills. Two experiments were undertaken, the first of which examined the relationship between cue utilization typologies and levels of accuracy following four simulated, power-off landing trials in a light aircraft simulator. The results indicated that higher levels of cue utilization were associated with a greater level of landing accuracy following training exposure. In the second study, participants’ levels of cue utilization were assessed prior to two 15 min periods during which they practiced take-offs and landings using a simulated unmanned aerial vehicle (UAV). Consistent with Study 1, the outcomes of Study 2 revealed a statistically significant relationship among levels of cue utilization and the number of trials to criterion on the take-off task, and the proportion of successful trials during both take-off and landing. In combination, the results suggest that the capacity for the acquisition and the subsequent utilization of cues is an important predictor of skill acquisition, particularly during the initial stages of the process. The implications for theory and applied practice are discussed. PMID:24917844

Current status of topical antiretroviral chemoprophylaxis.

PubMed

Van Damme, Lut; Szpir, Michael

2012-11-01

Recent studies suggest that the vaginal delivery of antiretroviral (ARV) agents - such as tenofovir, dapivirine and UC781 - may be a promising way to reduce the high rates of HIV infection among women in developing countries. This review examines these developments. The Microbicide Trials Network 003 study, a large phase IIb trial, was unable to show that daily dosing with 1% tenofovir vaginal gel was effective for HIV prevention. Nevertheless, preclinical and early-phase clinical trials suggest that ARV drugs - formulated in vaginal gels, rings, films, tablets and diaphragms - could be effective for HIV chemoprophylaxis. Investigations of topical chemoprophylaxis methods have seen mixed results in the past 12-18 months. Product adherence may prove to be one of the field's greatest challenges. Phase II and III trials continue to explore different dosing strategies for topical products that contain one or more ARV agents.

Education for contraceptive use by women after childbirth.

PubMed

Lopez, Laureen M; Grey, Thomas W; Hiller, Janet E; Chen, Mario

2015-07-29

Contraceptive education is generally a standard component of postpartum care, although the effectiveness is seldom examined. The assumptions that form the basis of such programs include postpartum women being motivated to use contraception and that they will not return to a health provider for family planning advice. Women may wish to discuss contraception both prenatally and after hospital discharge. Nonetheless, two-thirds of postpartum women have unmet needs for contraception. In the USA, many adolescents have repeat pregnancies within a year of giving birth. Assess the effectiveness of educational interventions for postpartum women on contraceptive use We searched for trials through June 2015 in PubMed, CENTRAL, CINAHL, POPLINE, and Web of Science. For current trials, we searched ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE and PsycInfo. We also examined reference lists of relevant articles. For earlier versions, we contacted investigators to locate additional reports. We considered randomized controlled trials (RCTs) that examined postpartum education about contraceptive use, whether delivered to individuals or to groups of women. Studies that randomized clusters rather than individuals were eligible if the investigators accounted for the clustering in the analysis. The intervention must have started within one month after delivery. We assessed titles and abstracts identified during the literature searches. The data were abstracted and entered into Review Manager. Studies were examined for methodological quality. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI) was calculated. Where data were sFor continuous variables, we computed the mean difference (MD) with 95% CI. Due to varied interventions and outcome measures, we did not conduct meta-analysis. Twelve trials met our eligibility criteria, included the three added in this update. The studies included a total of 4145 women. Eight trials were conducted in the USA; the others were from Australia, Nepal, Pakistan, and Syria. Four studies provided one session before hospital discharge; three had structured counseling of varying intensity and one involved informal counseling. Of eight interventions with than one contact, five focused on adolescents. Three of the five involved home visiting, one provided multiple clinic services, and one had in-person contact and phone follow-up. Of the remaining three for women of varying ages, two involved home visits and one provided phone follow-up.Our sensitivity analysis included six trials with evidence of moderate or high quality. In a study with adolescents, the group with home-based mentoring had fewer second births within two years compared to the control group (OR 0.41, 95% CI 0.17 to 1.00). The other five interventions had no effect. Of trials with lower quality evidence, two showed some effectiveness. In Nepal, women with an educational session immediately postpartum were more likely to use contraception at six months than those with a later or no session (OR 1.62, 95% CI 1.06 to 2.50). In an Australian study, teenagers in a structured home-visiting program were more likely to have effective contraception use at six months than those with standard home visits (OR 3.24; 95% CI 1.35 to 7.79). We focused our results summary on trials with moderate or high quality evidence. Overall, the overall quality of evidence in this review was moderate to low and the evidence of effectiveness was mostly low quality. The interventions could be improved by strengthening the program design and implementation. Some studies did not report program training for providers, adherence to the intervention protocol, or measurement of participants' knowledge and skills. Many trials did not have an objective outcome measure, i.e., pregnancy test or structured questionnaire for contraceptive use. Valid and reliable outcome measures are needed to obtain meaningful results. Still, given the associated costs and logistics, some programs would not be feasible in many settings.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

PubMed Central

Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001). Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001) and stable, large effect sizes (0.78 ±0.37). The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical trials for hypertension without any evidence of this increase impacting trial outcomes. Attempting to control placebo response in clinical trials for hypertension may not be necessary for successful efficacy outcomes. In exploratory analysis, we noted that despite finding significant relationships, none of the trial or patient characteristics we examined offered a clear explanation of the rise in placebo and stability in outcome measures over time. Collectively, these data suggest that the phenomenon of increasing placebo response and stable efficacy outcomes may be a general trend, occurring across trials for various psychiatric and medical conditions with physiological and non-physiological endpoints. PMID:29489874

A randomized clinical trial of the effectiveness of mechanical traction for sub-groups of patients with low back pain: study methods and rationale

PubMed Central

2010-01-01

Background Patients with signs of nerve root irritation represent a sub-group of those with low back pain who are at increased risk of persistent symptoms and progression to costly and invasive management strategies including surgery. A period of non-surgical management is recommended for most patients, but there is little evidence to guide non-surgical decision-making. We conducted a preliminary study examining the effectiveness of a treatment protocol of mechanical traction with extension-oriented activities for patients with low back pain and signs of nerve root irritation. The results suggested this approach may be effective, particularly in a more specific sub-group of patients. The aim of this study will be to examine the effectiveness of treatment that includes traction for patients with low back pain and signs of nerve root irritation, and within the pre-defined sub-group. Methods/Design The study will recruit 120 patients with low back pain and signs of nerve root irritation. Patients will be randomized to receive an extension-oriented treatment approach, with or without the addition of mechanical traction. Randomization will be stratified based on the presence of the pre-defined sub-grouping criteria. All patients will receive 12 physical therapy treatment sessions over 6 weeks. Follow-up assessments will occur after 6 weeks, 6 months, and 1 year. The primary outcome will be disability measured with a modified Oswestry questionnaire. Secondary outcomes will include self-reports of low back and leg pain intensity, quality of life, global rating of improvement, additional healthcare utilization, and work absence. Statistical analysis will be based on intention to treat principles and will use linear mixed model analysis to compare treatment groups, and examine the interaction between treatment and sub-grouping status. Discussion This trial will provide a methodologically rigorous evaluation of the effectiveness of using traction for patients with low back pain and signs of nerve root irritation, and will examine the validity of a pre-defined sub-grouping hypothesis. The results will provide evidence to inform non-surgical decision-making for these patients. Trial Registration This trial has been registered with http://ClinicalTrials.gov: NCT00942227 PMID:20433733

Impact of depressive symptoms, self-esteem and neuroticism on trajectories of overgeneral autobiographical memory over repeated trials.

PubMed

Kashdan, Todd B; Roberts, John E; Carlos, Erica L

2006-04-01

The present study examined trajectories of change in the frequency of overgeneral autobiographical memory (OGM) over the course of repeated trials, and tested whether particular dimensions of depressive symptomatology (somatic and cognitive-affective distress), self-esteem, and neuroticism account for individual differences in these trajectories. Given that depression is associated with impairments in effortful processing, we predicted that over repeated trials depression would be associated with increasingly OGM. Generalised Linear Mixed Models with Penalised Quasi-Likelihood demonstrated significant linear and quadratic trends in OGM over repeated trials, and somatic distress and self-esteem moderated these slopes. The form of these interactions suggested that somatic distress and low self-esteem primarily contribute to OGM during the second half of the trial sequence. The present findings demonstrate the value of a novel analytical approach to OGM that estimates individual trajectories of change over repeated trials.

Constructing common cohorts from trials with overlapping eligibility criteria: implications for comparing effect sizes between trials.

PubMed

Mount, David L; Feeney, Patricia; Fabricatore, Anthony N; Coday, Mace; Bahnson, Judy; Byington, Robert; Phelan, Suzanne; Wilmoth, Sharon; Knowler, William C; Hramiak, Irene; Osei, Kwame; Sweeney, Mary Ellen; Espeland, Mark A

2009-10-01

Comparing findings from separate trials is necessary to choose among treatment options, however differences among study cohorts may impede these comparisons. As a case study, to examine the overlap of study cohorts in two large randomized controlled clinical trials that assess interventions to reduce risk of major cardiovascular disease events in adults with type 2 diabetes in order to explore the feasibility of cross-trial comparisons The Action for Health in Diabetes (Look AHEAD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials enrolled 5145 and 10,251 adults with type 2 diabetes, respectively. Look AHEAD assesses the efficacy of an intensive lifestyle intervention designed to produce weight loss; ACCORD tests pharmacological therapies for control of glycemia, hyperlipidemia, and hypertension. Incidence of major cardiovascular disease events is the primary outcome for both trials. A sample was constructed to include participants from each trial who appeared to meet eligibility criteria and be appropriate candidates for the other trial's interventions. Demographic characteristics, health status, and outcomes of members and nonmembers of this constructed sample were compared. Nearly 80% of Look AHEAD participants were projected to be ineligible for ACCORD; ineligibility was primarily due to better glycemic control or no early history of cardiovascular disease. Approximately 30% of ACCORD participants were projected to be ineligible for Look AHEAD, often for reasons linked to poorer health. The characteristics of participants projected to be jointly eligible for both trials continued to reflect differences between trials according to factors likely linked to retention, adherence, and study outcomes. Accurate ascertainment of cross-trial eligibility was hampered by differences between protocols. Despite several similarities, the Look AHEAD and ACCORD cohorts represent distinct populations. Even within the subsets of participants who appear to be eligible and appropriate candidates for trials of both modes of intervention, differences remained. Direct comparisons of results from separate trials of lifestyle and pharmacologic interventions are compromised by marked differences in enrolled cohorts.

Association between study design and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist.

PubMed

Allareddy, Veerasathpurush; Lee, Min Kyeong; Shah, Andrea; Elangovan, Satheesh; Lin, Chin-Yu

2012-01-01

The scientific community views meta-analyses and systematic reviews, in addition to well-designed randomized controlled clinical trials, as the highest echelon in the continuum of hierarchy of evidence. The objective of this study was to examine the association between different study designs and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist. All articles, excluding editorial comments, letters to the editor, commentaries, and special articles, that were published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist during the years 2004 and 2005 were examined in this study. The number of times an article was cited in the first 24 months after its publication was computed. The PubMed database was used to index the study design of the articles. The association between study design and citation counts was examined using the Kruskal-Wallis test. A multivariable negative binomial regression model was used to examine the association between citation count and study design along with several other confounding variables. A total of 624 articles were selected for analysis. Of these, there were 25 meta-analyses or review articles, 42 randomized clinical trials, 59 clinical trials, 48 animal studies, 64 case reports, and 386 quasiexperimental/miscellaneous study designs. The mean ± SD citation count was 1.04 ± 1.46. Nearly half of the articles (n = 311) were not cited even once during the observation period. Case reports were cited less frequently than meta-analyses or reviews (incident risk ratio, 0.37; 95% confidence interval, 0.19 to 0.72; P = .003), even after adjusting for other independent variables. Among various study designs, meta-analyses and review articles are more likely to be cited in the first 24 months after publication. This study demonstrates the importance of publishing more meta-analyses and review articles for quicker dissemination of research findings.

Using Trial Vocal Fold Injection to Select Vocal Fold Scar Patients Who May Benefit From More Durable Augmentation.

PubMed

Carroll, Thomas L; Dezube, Aaron; Bauman, Laura A; Mallur, Pavan S

2018-02-01

Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar. Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation. Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 ( P < .05), for a delta VHI-10 of 8.3, or 30.9% improvement. Twelve of the 15 (80%) showed a clinically significant improvement (delta VHI-10 >5). A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.

The impact of defendant ethnicity on the psycholegal opinions of forensic mental health evaluators.

PubMed

McCallum, Katherine E; MacLean, Nina; Neil Gowensmith, W

2015-01-01

The impact of ethnicity on clinicians' decision making has received a great deal of attention and research. Several studies have documented that client ethnicity significantly influences diagnoses, testing and assessment protocols, recommendations for treatment, and expected outcomes. However, there is limited research examining the impact of a criminal defendant's ethnicity upon forensic mental health experts. To examine this issue, the authors reviewed 816 forensic reports on competency to stand trial submitted to the Hawaii judiciary between 2007 and 2008 and compared recommendation rates across categories of defendant ethnicity. Significant differences between ethnic groups were found in recommendations of competency to stand trial. Specifically, Asian misdemeanant populations were found to be incompetent to stand trial at higher rates than other ethnic groups. These findings highlight the potential impact that ethnicity may have on clinicians' decision making in certain forensic settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-pharmacologic labour pain relief.

PubMed

Prasertcharoensuk, Witoon; Thinkhamrop, Jadsada

2004-10-01

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of alternative and complementary therapies for pain management in labour. To examine the effectiveness of complementary and alternative therapies for pain management in labour on maternal and perinatal morbidity. The trials included three trials of hypnosis (n = 189), one involving audio-analgesia (n = 25), one involving (n = 22), and one trial of music (n = 30). Women receiving hypnosis were more satisfied with their pain management in labour compared with controls (RR 2.33, 95% CI 1.55 to 4.71). No differences were seen for women recieving, music or audio analgesia. Hypnosis may be beneficial for the management of pain during labour. However, few complementary therapies have been subjected to proper scientific study.

Obsessive-compulsive tendencies are associated with a focused information processing strategy.

PubMed

Soref, Assaf; Dar, Reuven; Argov, Galit; Meiran, Nachshon

2008-12-01

The study examined the hypothesis that obsessive-compulsive (OC) tendencies are related to a reliance on focused and serial rather than a parallel, speed-oriented information processing style. Ten students with high OC tendencies and 10 students with low OC tendencies performed the flanker task, in which they were required to quickly classify a briefly presented target letter (S or H) that was flanked by compatible (e.g., SSSSS) or incompatible (e.g., HHSHH) noise letters. Participants received 4 blocks of 100 trials each, two with 50% compatible trials and two with 80% compatible trials and were informed of the probability of compatible trials before the beginning of each block. As predicted, high OC participants, as compared to low OC participants, had slower overall reaction time (RT) and lower tendency for parallel processing (defined as incompatible trials RT minus compatible trials RT). Low, more than high OC participants tended to adjust their focused/parallel processing including a shift towards parallel processing in blocks with 80% compatible trials and in trials following compatible trials. Implications of these results to the cognitive theory and therapy of OCD are discussed.

Systematic review and meta-analysis of interventions targeting sleep and their impact on child body mass index, diet, and physical activity.

PubMed

Yoong, Sze Lin; Chai, Li Kheng; Williams, Christopher M; Wiggers, John; Finch, Meghan; Wolfenden, Luke

2016-05-01

This review aimed to examine the impact of interventions involving an explicit sleep component on child body mass index (BMI), diet, and physical activity. A systematic search was undertaken in six databases to identify randomized controlled trials examining the impact of interventions with a sleep component on child BMI, dietary intake, and/or physical activity. A random effects meta-analysis was conducted assessing the impact of included interventions on child BMI. Of the eight included trials, three enforced a sleep protocol and five targeted sleep as part of multicomponent behavioral interventions either exclusively or together with nutrition and physical activity. Meta-analysis of three studies found that multicomponent behavioral interventions involving a sleep component were not significantly effective in changing child BMI (n = 360,-0.04 kg/m(2) [-0.18, 0.11], I(2)  = 0%); however, only one study included in the meta-analysis successfully changed sleep duration in children. There were some reported improvements to adolescent diet, and only one trial examined the impact on child physical activity, where a significant effect was observed. Findings from the included studies suggest that where improvements in child sleep duration were achieved, a positive impact on child BMI, nutrition, and physical activity was also observed. © 2016 The Obesity Society.

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety.

PubMed

McMakin, Dana L; Ricketts, Emily J; Forbes, Erika E; Silk, Jennifer S; Ladouceur, Cecile D; Siegle, Greg J; Milbert, Melissa; Trubnick, Laura; Cousins, Jennifer C; Ryan, Neal D; Harvey, Allison G; Dahl, Ronald E

2018-06-06

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9-14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9-14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.

Diclofenac Potassium in Acute Postoperative Pain and Dysmenorrhoea: Results from Comprehensive Clinical Trial Reports

PubMed Central

2018-01-01

We compared the efficacy of diclofenac potassium in unpublished clinical study reports (CSRs) and published reports to examine publication bias, industry bias, and comprehensiveness. Novartis provided CSRs of randomised double-blind trials of diclofenac potassium involving postoperative patients following third molar extraction (3 trials, n=519), gynaecological surgery (3 trials, n=679), and dysmenorrhoea (2 trials, n=711) conducted in 1988–1990. Searches identified published reports of 6 trials. Information from 599/1909 patients was not published; trials with 846/1909 patients were published in a defunct journal. Greater methodological information in CSRs contributed to lesser risk of bias than published trials. Numbers needed to treat (NNT) from CSRs for all six postoperative trials for at least 50% of maximum pain relief over 6 h were 2.2 (95% confidence interval, 1.9–2.6) and 2.1 (1.8–2.4) for 50 and 100 mg diclofenac potassium, respectively. A Cochrane review of published trial data reported NNTs of 2.1 and 1.9, and one comprehensive analysis reported NNTs of 2.2 and 2.1, respectively. All analyses had similar results for patients remedicating within 8 h. No data from dysmenorrhoea CSRs appeared in a Cochrane review. CSRs provide useful information and increase confidence. Stable efficacy estimates with standard study designs reduce the need for updating reviews. PMID:29623148

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

PubMed

Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

2018-03-01

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department.

PubMed

Reynolds, Stacy L; Studnek, Jonathan R; Bryant, Kathleen; VanderHave, Kelly; Grossman, Eric; Moore, Charity G; Young, James; Hogg, Melanie; Runyon, Michael S

2016-09-08

Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. NCT02521415. 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/

Effect of a facility-based multifaceted intervention on the quality of obstetrical care: a cluster randomized controlled trial in Mali and Senegal

PubMed Central

2013-01-01

Background Maternal mortality in referral hospitals in Mali and Senegal surpasses 1% of obstetrical admissions. Poor quality obstetrical care contributes to high maternal mortality; however, poor care is often linked to insufficient hospital resources. One promising method to improve obstetrical care is maternal death review. With a cluster randomized trial, we assessed whether an intervention, based on maternal death review, could improve obstetrical quality of care. Methods The trial began with a pre-intervention year (2007), followed by two years of intervention activities and a post-intervention year. We measured obstetrical quality of care in the post-intervention year using a criterion-based clinical audit (CBCA). We collected data from 32 of the 46 trial hospitals (16 in each trial arm) and included 658 patients admitted to the maternity unit with a trial of labour. The CBCA questionnaire measured 5 dimensions of care- patient history, clinical examination, laboratory examination, delivery care and postpartum monitoring. We used adjusted mixed models to evaluate differences in CBCA scores by trial arms and examined how levels of hospital human and material resources affect quality of care differences associated with the intervention. Results For all women, the mean percentage of care criteria met was 66.3 (SD 13.5). There were significantly greater mean CBCA scores in women treated at intervention hospitals (68.2) compared to control hospitals (64.5). After adjustment, women treated at intervention sites had 5 points’ greater scores than those at control sites. This difference was mostly attributable to greater clinical examination and post-partum monitoring scores. The association between the intervention and quality of care was the same, irrespective of the level of resources available to a hospital; however, as resources increased, so did quality of care scores in both arms of the trial. Trial registration The QUARITE trial is registered on the Current Controlled Trials website under ISRCTN46950658 PMID:23351269

Quality of Reporting Randomized Controlled Trials in Five Leading Neurology Journals in 2008 and 2013 Using the Modified "Risk of Bias" Tool.

PubMed

Zhai, Xiao; Cui, Jin; Wang, Yiran; Qu, Zhiquan; Mu, Qingchun; Li, Peiwen; Zhang, Chaochao; Yang, Mingyuan; Chen, Xiao; Chen, Ziqiang; Li, Ming

2017-03-01

To examine the risk of bias of methodological quality of reporting randomized clinical trials (RCTs) in major neurology journals before and after the update (2011) of Cochrane risk of bias tool. RCTs in 5 leading neurology journals in 2008 and 2013 were searched systematically. Characteristics were extracted based on the list of the modified Cochrane Collaboration's tool. Country, number of patients, type of intervention, and funding source also were examined for further analysis. A total of 138 RCTs were enrolled in this study. The rates of following a trial plan were 61.6% for the allocation generation, 52.9% for the allocation concealment, 84.8% for the blinding of the participants or the personnel, 34.8% for the blinding of outcome assessment, 78.3% for the incomplete outcome data, and 67.4% for the selective reporting. A significant setback was found in "the selective reporting" in 2013 than that in 2008. Trials performed by multi-centers and on a large scale had significantly more "low risk of bias" trials. Not only the number of surgical trials (5.8%) was much less than that of trials using drugs (73.9%), but also the reporting quality of surgical trials were worse (P = 0.008). Finally, only 17.4% trials met the criterion of "low risk of bias." The modified "risk of bias" tool is an improved version for assessment. Methodological quality of reporting RCTs in the 5neurology journals is unsatisfactory, especially that for surgical RCTs, and it could be further improved. Copyright © 2017 Elsevier Inc. All rights reserved.

Protocol for Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial: a randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services

PubMed Central

2011-01-01

Background Dental caries is a persistent public health problem with little change in the prevalence in young children over the last 20 years. Once a child contracts the disease it has a significant impact on their quality of life. There is good evidence from Cochrane reviews including trials that fluoride varnish and regular use of fluoride toothpaste can prevent caries. The Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial will compare the costs and effects of a caries preventive package (fluoride varnish, toothpaste, toothbrush and standardised dental health education) with dental health education alone in young children. Methods/Design A randomised controlled trial on children initially aged 2 and 3 years old who are regular attenders at the primary dental care services in Northern Ireland. Children will be recruited and randomised in dental practices. Children will be randomised to the prevention package of both fluoride varnish (twice per year for three years), fluoride toothpaste (1,450 ppm F) (supplied twice per year), a toothbrush (supplied twice a year) or not; both test and control groups receive standardised dental health education delivered by the dentist twice per year. Randomisation will be conducted by the Belfast Trust Clinical Research Support Centre ([CRSC] a Clinical Trials Unit). 1200 participants will be recruited from approximately 40 dental practices. Children will be examined for caries by independent dental examiners at baseline and will be excluded if they have caries. The independent dental examiners will examine the children again at 3 years blinded to study group. The primary end-point is whether the child develops caries (cavitation into dentine) or not over the three years. One secondary outcome is the number of carious surfaces in the primary dentition in children who experience caries. Other secondary outcomes are episodes of pain, extraction of primary teeth, other adverse events and costs which will be obtained from parental questionnaires. Discussion This is a pragmatic trial conducted in general dental practice. It tests a composite caries prevention intervention, which represents an evidence based approach advocated by current guidance from the English Department of Health which is feasible to deliver to all low risk (caries free) children in general dental practice. The trial will provide valuable information to policy makers and clinicians on the costs and effects of caries prevention delivered to young children in general dental practice. Trial registration EudraCT No: 2009 - 010725 - 39 ISRCTN: ISRCTN36180119 Ethics Reference No: 09/H1008/93: PMID:21985746

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

A systematic review of commercial weight loss programmes' effect on glycemic outcomes among overweight and obese adults with and without type 2 diabetes mellitus.

PubMed

Chaudhry, Z W; Doshi, R S; Mehta, A K; Jacobs, D K; Vakil, R M; Lee, C J; Bleich, S N; Kalyani, R R; Clark, J M; Gudzune, K A

2016-08-01

We examined the glycemic benefits of commercial weight loss programmes as compared with control/education or counselling among overweight and obese adults with and without type 2 diabetes mellitus (T2DM). We searched MEDLINE, Cochrane Database of Systematic Reviews, and references cited by individual programmes. We included randomized controlled trials of ≥12 weeks duration. Two reviewers extracted information on study design, population characteristics, interventions, and mean changes in haemoglobin A1c and glucose. We included 18 randomized controlled trials. Few trials occurred among individuals with T2DM. In this population, Jenny Craig reduced A1c at least 0.4% more than counselling at 12 months, Nutrisystem significantly reduced A1c 0.3% more than counselling at 6 months, and OPTIFAST reduced A1c 0.3% more than counselling at 6 months. Among individuals without T2DM, few studies evaluated glycemic outcomes, and when reported, most did not show substantial reductions. Few trials have examined whether commercial weight loss programmes result in glycemic benefits for their participants, particularly among overweight and obese individuals without T2DM. Jenny Craig, Nutrisystem and OPTIFAST show promising glycemic lowering benefits for patients with T2DM, although additional studies are needed to confirm these conclusions. © 2016 World Obesity. © 2016 World Obesity.

A randomized controlled trial of culturally adapted motivational interviewing for Hispanic heavy drinkers: Theory of Adaptation and Study Protocol

PubMed Central

Lee, Christina S.; Colby, Suzanne M.; Magill, Molly; Almeida, Joanna; Tavares, Tonya; Rohsenow, Damaris J.

2016-01-01

Background The NIH Strategic Plan prioritizes health disparities research for socially disadvantaged Hispanics, to reduce the disproportionate burden of alcohol-related negative consequences compared to other racial/ethnic groups. Cultural adaptation of evidence-based treatments, such as motivational interviewing (MI), can improve access and response to alcohol treatment. However, the lack of rigorous clinical trials designed to test the efficacy and theoretical underpinnings of cultural adaptation has made proof of concept difficult. Objective The CAMI2 (Culturally Adapted Motivational Interviewing) study design and its theoretical model, is described to illustrate how MI adapted to social and cultural factors (CAMI) can be discriminated against non-adapted MI. Methods and Design CAMI2, a large, 12 month randomized prospective trial, examines the efficacy of CAMI and MI among heavy drinking Hispanics recruited from the community (n=257). Outcomes are reductions in heavy drinking days (Time Line Follow-Back) and negative consequences of drinking among Hispanics (Drinkers Inventory of Consequences). A second aim examines perceived acculturation stress as a moderator of treatment outcomes in the CAMI condition. Summary The CAMI2 study design protocol is presented and the theory of adaptation is presented. Findings from the trial described may yield important recommendations on the science of cultural adaptation and improve MI dissemination to Hispanics with alcohol risk. PMID:27565832

Bellwether Social Studies Programs.

ERIC Educational Resources Information Center

Daetz, Denney

1985-01-01

Describes and reviews commercially-available computer software for social studies (SS). They are: "Jury Trial II" (utilizes artificial intelligence); "Africa" (utilizes creative graphics to teaching SS facts; "Revolutions: Past, Present and Future"; "The Other Side" (examines world peace using values…

Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Taheri, Shahrad; Chagoury, Odette; Zaghloul, Hadeel; Elhadad, Sara; Ahmed, Salma Hayder; Omar, Omar; Payra, Sherryl; Ahmed, Salma; El Khatib, Neda; Amona, Rasha Abou; El Nahas, Katie; Bolton, Matthew; Chaar, Henem; Suleiman, Noor; Jayyousi, Amin; Zirie, Mahmoud; Janahi, Ibrahim; Elhag, Wahiba; Alnaama, Abdulla; Zainel, Abduljaleel; Hassan, Dahlia; Cable, Tim; Charlson, Mary; Wells, Martin; Al-Hamaq, Abdulla; Al-Abdulla, Samya; Abou-Samra, Abdul Badi

2018-05-21

Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM. The planned study is an ongoing, non-blinded, pragmatic, randomised controlled, parallel-group trial examining the impact of an LED-based ILI on body weight and diabetes remission in younger (18-50 years) T2DM individuals with early diabetes (≤ 3-year duration). The ILI will be compared to usual medical care (UMC). The primary outcome will be weight loss at 12 months. Other key outcomes of interest include diabetes remission, glycaemic control, diabetes complications, cardiovascular health, physical activity, mental health, and quality of life. It is planned for the study to include 138 subjects for assessment of the primary outcome. Safety will be assessed throughout. If DIADEM-I demonstrates a clinically significant effect for younger individuals with early T2DM, it will inform clinical guidelines and services of the future for management of T2DM. ISRCTN: ISRCTN20754766 (date assigned: 7 June 2017); ClinicalTrials.gov, ID: NCT03225339 Registered on 26 June 2017.

Do personalised e-mail invitations increase the response rates of breast cancer survivors invited to participate in a web-based behaviour change intervention? A quasi-randomised 2-arm controlled trial.

PubMed

Short, Camille E; Rebar, Amanda L; Vandelanotte, Corneel

2015-08-19

Previous research has shown that the personalisation of study invitations improves response rates in survey-based research. To examine if this finding extends to experimental studies, we examined the impact of personalised study invitation e-mails on the response rates of potentially eligible breast cancer survivors for participation in a 6 month randomised controlled trial testing the efficacy of a physical activity intervention. Potential participants (n = 344) were sent either a personalised email or a generic email. Those sent the personalised email were 1.5 times (95 % CI = 1.18-1.93) more likely to respond than those sent the generic email. These findings suggest that personalisation may be a useful and potentially powerful tool that can be utilised when recruiting participants into experimental studies in order to boost response rates.

Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

PubMed Central

2011-01-01

Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD). Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805. PMID:21992747

Examining the Efficacy of the Modified Story Memory Technique (mSMT) in Persons With TBI Using Functional Magnetic Resonance Imaging (fMRI): The TBI-MEM Trial.

PubMed

Chiaravalloti, Nancy D; Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John

2015-01-01

New learning and memory deficits are common following traumatic brain injury (TBI). Yet few studies have examined the efficacy of memory retraining in TBI through the most methodologically vigorous randomized clinical trial. Our previous research has demonstrated that the modified Story Memory Technique (mSMT) significantly improves new learning and memory in multiple sclerosis. The present double-blind, placebo-controlled, randomized clinical trial examined changes in cerebral activation on functional magnetic resonance imaging following mSMT treatment in persons with TBI. Eighteen individuals with TBI were randomly assigned to treatment (n = 9) or placebo (n = 9) groups. Baseline and follow-up functional magnetic resonance imaging was collected during a list-learning task. Significant differences in cerebral activation from before to after treatment were noted in regions belonging to the default mode network and executive control network in the treatment group only. Results are interpreted in light of these networks. Activation differences between the groups likely reflect increased use of strategies taught during treatment. This study demonstrates a significant change in cerebral activation resulting from the mSMT in a TBI sample. Findings are consistent with previous work in multiple sclerosis. Behavioral interventions can show significant changes in the brain, validating clinical utility.

Motivation for health information seeking and processing about clinical trial enrollment.

PubMed

Yang, Z Janet; McComas, Katherine; Gay, Geri; Leonard, John P; Dannenberg, Andrew J; Dillon, Hildy

2010-07-01

Low patient accrual in clinical trials poses serious concerns for the advancement of medical science in the United States. Past research has identified health communication as a crucial step in overcoming barriers to enrollment. However, few communication scholars have studied this problem from a sociopsychological perspective to understand what motivates people to look for or pay attention to information about clinical trial enrollment. This study applies the model of Risk Information Seeking and Processing (RISP) to this context of health decision making. By recognizing the uncertainties embedded in clinical trials, we view clinical trial enrollment as a case study of risk. With data from a random-digit-dial telephone survey of 500 adults living in the United States, we used structural equation modeling to test the central part of the RISP model. In particular, we examined the role of optimistic feelings, as a type of positive affect, in motivating information seeking and processing. Our results indicated that rather than exerting an indirect influence on information seeking through motivating a psychological need for more information, optimistic feelings have more direct relationships with information seeking and processing. Similarly, informational subjective norms also exhibit a more direct relationship with information seeking and processing. These results suggest merit in applying the RISP model to study health decision making related to clinical trial enrollment. Our findings also render practical implications on how to improve communication about clinical trial enrollment.

Examining pretrial publicity in a shadow jury paradigm: issues of slant, quantity, persistence and generalizability.

PubMed

Daftary-Kapur, Tarika; Penrod, Steven D; O'Connor, Maureen; Wallace, Brian

2014-10-01

The purpose of this study was to examine the influence of pretrial publicity (PTP) on mock juror decision making. Specifically, we examined the influence of quantity and slant of the PTP (proprosecution vs. prodefense), the persistence of PTP effects over time, and whether the PTP effects demonstrated in research laboratories would also occur in more naturalistic settings (generalizability). Using a shadow jury paradigm we examined these effects using a real trial as stimulus. Mock jurors included 115 jury-eligible community members who were naturally exposed to PTP in the venue in which the actual case occurred and 156 who were experimentally exposed. We found mock jurors were significantly influenced by both the slant and quantity of the PTP to which they were exposed, such that those exposed to proprosecution or prodefense PTP tended to render decision in support of the party favored in the PTP, and those exposed to greater quantities of PTP tended to be more biased. Additionally, PTP effects persisted throughout the course of the trial and continued to influence judgments in face of trial evidence and arguments. A finding of no significant difference in the effect of exposure slant between the naturally exposed and experimentally exposed samples provides support for the external validity of laboratory studies examining PTP effects. This research helps address some of the concerns raised by courts with regard to the durability of PTP effects and the application of laboratory findings to real world settings. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Complementary and alternative therapies for pain management in labour.

PubMed

Smith, C A; Collins, C T; Cyna, A M; Crowther, C A

2003-01-01

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of alternative and complementary therapies for pain management in labour. To examine the effectiveness of complementary and alternative therapies for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to July 2002), EMBASE (1980 to July 2002) and CINAHL (1980 to July 2002). The inclusion criteria included published and unpublished randomised controlled trials comparing complementary and alternative therapies with placebo, no treatment or pharmacological forms of pain management in labour. All women whether primiparous or multiparous, and in spontaneous or induced labour, in the first and second stage of labour were included. Meta-analysis was performed using relative risks for dichotomous outcomes and weighted mean differences for continuous outcomes. The outcome measures were maternal satisfaction, use of pharmacological pain relief and maternal and neonatal adverse outcomes. Seven trials involving 366 women and using different modalities of pain management were included in this review. The trials included one involving acupuncture (n = 100), one involving audio-analgesia (n = 25), one involving aromatherapy (n = 22), three trials of hypnosis (n = 189) and one trial of music (n = 30). The trial of acupuncture decreased the need for pain relief (relative risk (RR) 0.56, 95% confidence interval (CI) 0.39 to 0.81). Women receiving hypnosis were more satisfied with their pain management in labour compared with controls (RR 2.33, 95% CI 1.55 to 4.71). No differences were seen for women receiving aromatherapy, music or audio analgesia. Acupuncture and hypnosis may be beneficial for the management of pain during labour. However, few complementary therapies have been subjected to proper scientific study and the number of women studied is small.

Disclosure of amyloid status is not a barrier to recruitment in preclinical Alzheimer’s disease clinical trials

PubMed Central

Grill, Joshua; Zhou, Yan; Elashoff, David; Karlawish, Jason

2016-01-01

Preclinical Alzheimer’s disease (AD) clinical trials may require participants to learn if they meet biomarker enrollment criteria to enroll. To examine whether this requirement will impact trial recruitment, we presented 132 older community volunteers who self-reported normal cognition with one of two hypothetical informed consent forms (ICF) describing an AD prevention clinical trial. Both ICFs described amyloid Positron Emission Tomography (PET) scans. One ICF stated that scan results would not be shared with the participants (blinded enrollment); the other stated that only persons with elevated amyloid would be eligible (transparent enrollment). Participants rated their likelihood of enrollment and completed an interview with a research assistant. We found no difference between the groups in willingness to participate. Study risks and the requirement of a study partner were reported as the most important factors in the decision whether to enroll. The requirement of biomarker disclosure may not slow recruitment to preclinical AD trials. PMID:26923411

Identifying Learning Patterns of Children at Risk for Specific Reading Disability

PubMed Central

Barbot, Baptiste; Krivulskaya, Suzanna; Hein, Sascha; Reich, Jodi; Thuma, Philip E.; Grigorenko, Elena L.

2016-01-01

Differences in learning patterns of vocabulary acquisition in children at risk (+SRD) and not at risk (SRD) for Specific Reading Disability (SRD) were examined using a microdevelopmental paradigm applied to the multi-trial Foreign Language Learning Task (FLLT; Baddeley et al., 1995). The FLLT was administered to 905 children from rural Chitonga-speaking Zambia. A multi-group Latent Growth Curve Model (LGCM) was implemented to study interindividual differences in intraindividual change across trials. Results showed that the +SRD group recalled fewer words correctly in the first trial, learned at a slower rate during the subsequent trials, and demonstrated a more linear learning pattern compared to the SRD group. This study illustrates the promise of LGCM applied to multi-trial learning tasks, by isolating three components of the learning process (initial recall, rate of learning, and functional pattern of learning). Implications of this microdevelopmental approach to SRD research in low-to-middle income countries are discussed. PMID:26037654

Identifying learning patterns of children at risk for Specific Reading Disability.

PubMed

Barbot, Baptiste; Krivulskaya, Suzanna; Hein, Sascha; Reich, Jodi; Thuma, Philip E; Grigorenko, Elena L

2016-05-01

Differences in learning patterns of vocabulary acquisition in children at risk (+SRD) and not at risk (-SRD) for Specific Reading Disability (SRD) were examined using a microdevelopmental paradigm applied to the multi-trial Foreign Language Learning Task (FLLT; Baddeley et al., 1995). The FLLT was administered to 905 children from rural Chitonga-speaking Zambia. A multi-group Latent Growth Curve Model (LGCM) was implemented to study interindividual differences in intraindividual change across trials. Results showed that the +SRD group recalled fewer words correctly in the first trial, learned at a slower rate during the subsequent trials, and demonstrated a more linear learning pattern compared to the -SRD group. This study illustrates the promise of LGCM applied to multi-trial learning tasks, by isolating three components of the learning process (initial recall, rate of learning, and functional pattern of learning). Implications of this microdevelopmental approach to SRD research in low-to-middle income countries are discussed. © 2015 John Wiley & Sons Ltd.

Efficacy of Chinese herbal medicine for stroke modifiable risk factors: a systematic review.

PubMed

Peng, Wenbo; Lauche, Romy; Ferguson, Caleb; Frawley, Jane; Adams, Jon; Sibbritt, David

2017-01-01

The vast majority of stroke burden is attributable to its modifiable risk factors. This paper aimed to systematically summarise the evidence of Chinese herbal medicine (CHM) interventions on stroke modifiable risk factors for stroke prevention. A literature search was conducted via the MEDLINE, CINAHL/EBSCO, SCOPUS, and Cochrane Database from 1996 to 2016. Randomised controlled trials or cross-over studies were included. Risk of bias was assessed according to the Cochrane Risk of Bias tool. A total of 46 trials (6895 participants) were identified regarding the use of CHM interventions in the management of stroke risk factors, including 12 trials for hypertension, 10 trials for diabetes, eight trials for hyperlipidemia, seven trials for impaired glucose tolerance, three trials for obesity, and six trials for combined risk factors. Amongst the included trials with diverse study design, an intervention of CHM as a supplement to biomedicine and/or a lifestyle intervention was found to be more effective in lowering blood pressure, decreasing blood glucose level, helping impaired glucose tolerance reverse to normal, and/or reducing body weight compared to CHM monotherapy. While no trial reported deaths amongst the CHM groups, some papers do report moderate adverse effects associated with CHM use. However, the findings of such beneficial effects of CHM should be interpreted with caution due to the heterogeneous set of complex CHM studied, the various control interventions employed, the use of different participants' inclusion criteria, and low methodological quality across the published studies. The risk of bias of trials identified was largely unclear in the domains of selection bias and detection bias across the included studies. This study showed substantial evidence of varied CHM interventions improving the stroke modifiable risk factors. More rigorous research examining the use of CHM products for sole or multiple major stroke risk factors are warranted.

A Randomized Trial Examining the Effects of Conjoint Behavioral Consultation in Rural Schools: Student Outcomes and the Mediating Role of the Teacher-Parent Relationship

ERIC Educational Resources Information Center

Sheridan, Susan M.; Witte, Amanda L.; Holmes, Shannon R.; Coutts, Michael J.; Dent, Amy L.; Kunz, Gina M.; Wu, ChaoRong

2017-01-01

The results of a large-scale randomized controlled trial of Conjoint Behavioral Consultation (CBC) on student outcomes and teacher-parent relationships in rural schools are presented. CBC is an indirect service delivery model that addresses concerns shared by teachers and parents about students. In the present study, the intervention was aimed at…

Is Reducing Uncertain Control the Key to Successful Test Anxiety Intervention for Secondary School Students? Findings from a Randomized Control Trial

ERIC Educational Resources Information Center

Putwain, David W.; Pescod, Marc

2018-01-01

The aim of the study was to conduct a randomized control trial of a targeted, facilitated, test anxiety intervention for a group of adolescent students, and to examine the mediating role of uncertain control. Fifty-six participants (male = 19, white = 21, mean age = 14.7 years) were randomly allocated to an early intervention or wait-list control…

Presence of music while eating: Effects on energy intake, eating rate and appetite sensations.

PubMed

Mamalaki, Eirini; Zachari, Konstantina; Karfopoulou, Eleni; Zervas, Efthimios; Yannakoulia, Mary

2017-01-01

The role of music in energy and dietary intake of humans is poorly understood. The purpose of the present laboratory study was to examine the effect of background music, its presence and its intensity, on energy intake, eating rate and appetite feelings. The study had a randomized crossover design. Twenty-six normal weight and overweight/obese men participated in random order in three trials: the control trial (no music was playing), the 60dB and the 90dB music trials, while an ad libitum lunch was consumed. Visual analogue scales for hunger, fullness/satiety, as well as desire to eat were administered to the participants. Energy intake at the ad libitum lunch did not differ between trials, even when covariates were taken into account. There were no statistically significant differences between trials on meal characteristics, such as meal duration, number of servings, number of bites eaten and on appetite indices. Future studies are needed to replicate these results and investigate the effect of different types of music and/or sound. Copyright © 2016 Elsevier Inc. All rights reserved.

Trial-to-trial fluctuations in attentional state and their relation to intelligence.

PubMed

Unsworth, Nash; McMillan, Brittany D

2014-05-01

Trial-to-trial fluctuations in attentional state while performing measures of intelligence were examined in the current study. Participants performed various measures of fluid and crystallized intelligence while also providing attentional state ratings prior to each trial. It was found that pre-trial attentional state ratings strongly predicted subsequent trial performance on the fluid intelligence measures, such that when participants rated their current attentional state as highly focused on the current task, performance tended to be high compared to when participants reported their current attentional state as being low and unfocused on the current task. Furthermore, overall attentional state ratings and variability in attentional state ratings were moderately correlated with overall levels of performance on the fluid intelligence measures. However, attentional state ratings did not predict performance on the measure of crystallized intelligence. These results suggest a strong link between variation in attention state and variation in fluid intelligence as postulated by a number of recent theories. PsycINFO Database Record (c) 2014 APA, all rights reserved.

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

PubMed

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

2018-05-07

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

Complementary and alternative therapies for pain management in labour.

PubMed

Smith, C A; Collins, C T; Cyna, A M; Crowther, C A

2006-10-18

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of alternative and complementary therapies for pain management in labour. To examine the effects of complementary and alternative therapies for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006) and CINAHL (1980 to February 2006). The inclusion criteria included published and unpublished randomised controlled trials comparing complementary and alternative therapies (but not biofeedback) with placebo, no treatment or pharmacological forms of pain management in labour. All women whether primiparous or multiparous, and in spontaneous or induced labour, in the first and second stage of labour were included. Meta-analysis was performed using relative risks for dichotomous outcomes and mean differences for continuous outcomes. The outcome measures were maternal satisfaction, use of pharmacological pain relief and maternal and neonatal adverse outcomes. Fourteen trials were included in the review with data reporting on 1537 women using different modalities of pain management; 1448 women were included in the meta-analysis. Three trials involved acupuncture (n = 496), one audio-analgesia (n = 24), two trials acupressure (n = 172), one aromatherapy (n = 22), five trials hypnosis (n = 729), one trial of massage (n = 60), and relaxation (n = 34). The trials of acupuncture showed a decreased need for pain relief (relative risk (RR) 0.70, 95% confidence interval (CI) 0.49 to 1.00, two trials 288 women). Women taught self-hypnosis had decreased requirements for pharmacological analgesia (RR 0.53, 95% CI 0.36 to 0.79, five trials 749 women) including epidural analgesia (RR 0.30, 95% CI 0.22 to 0.40) and were more satisfied with their pain management in labour compared with controls (RR 2.33, 95% CI 1.15 to 4.71, one trial). No differences were seen for women receiving aromatherapy, or audio analgesia. Acupuncture and hypnosis may be beneficial for the management of pain during labour; however, the number of women studied has been small. Few other complementary therapies have been subjected to proper scientific study.

Applying New Methods to the Measurement of Fidelity of Implementation: Examining the Critical Ingredients of the Responsive Classroom Approach in Relation to Mathematics Achievement

ERIC Educational Resources Information Center

Abry, Tashia D. S.; Rimm-Kaufman, Sara E.; Larsen, Ross A.; Brewer, Alix J.

2011-01-01

The present study examines data collected during the second year of a three-year longitudinal cluster randomized controlled trial, the Responsive Classroom Efficacy Study (RCES). In the context of and RCT, the research questions address naturally occurring variability in the independent variables of interest (i.e., teachers' (fidelity of…

Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice.

PubMed

Brænd, Anja Maria; Straand, Jørund; Jakobsen, Rune Bruhn; Klovning, Atle

2016-04-11

Previously, we identified a 10-year cohort of protocols from applications to the Norwegian Medicines Agency 1998-2007, consisting of 196 drug trials in general practice. The aim of this study was to examine whether trial results were published and whether trial funding and conflicts of interest were reported. Cohort study of trials with systematic searches for published results. Clinical drug trials in Norwegian general practice. We performed systematic literature searches of MEDLINE, Embase and CENTRAL to identify publications originating from each trial using characteristics such as test drug, comparator and patient groups as search terms. When no publication was identified, we contacted trial sponsors for information regarding trial completion and reference to any publications. We determined the frequency of publication of trial results and trial characteristics associated with publication of results. Of the 196 trials, 5 were never started. Of the remaining 191 trials, 71% had results published in a journal, 11% had results publicly available elsewhere and 18% of trials had no results available. Publication was more common among trials with an active comparator drug (χ(2) test, p=0.040), with a larger number of patients (total sample size≥median, p=0.010) and with a longer trial period (duration≥median, p=0.025). Trial funding was reported in 85% of publications and increased over time, as did reporting of conflicts of interest among authors. Among the 134 main journal articles from the trials, 60% presented statistically significant results for the investigational drug, and the conclusion of the article was favourable towards the test drug in 78% of papers. We did not identify any journal publication of results for 29% of the general practice drug trials. Trials with an active comparator, larger and longer trials were more likely to be published. 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/

Maintenance ECT in schizophrenia: A systematic review.

PubMed

Ward, Heather Burrell; Szabo, Steven T; Rakesh, Gopalkumar

2018-03-20

Relapse after discontinuation of ECT is significant in patients with schizophrenia. The purpose of this systematic review was to examine use of M-ECT in schizophrenia to guide clinical decision making for relapse prevention in schizophrenia. We reviewed studies examining the role of continuation (C-ECT) and maintenance electroconvulsive therapy (M-ECT) in schizophrenia. Following PRISMA guidelines, we included randomized controlled trials, open label trials, retrospective chart reviews, case reports, and case series in this review. We evaluated adjunctive pharmacological regimens; ECT treatment parameters, including frequency, duration of continued treatment, electrode placement; clinical outcomes including cognitive side effects and relapse rates from included studies. Our findings suggest M-ECT could provide an effective form of relapse prevention in these patients and persistent cognitive side effects are minimal. Copyright © 2018 Elsevier B.V. All rights reserved.

Communication skills in the training of psychiatrists: A systematic review of current approaches.

PubMed

Ditton-Phare, Philippa; Loughland, Carmel; Duvivier, Robbert; Kelly, Brian

2017-07-01

A range of communication skills training programmes have been developed targeting trainees in various medical specialties, predominantly in oncology but to a lesser extent in psychiatry. Effective communication is fundamental to the assessment and treatment of psychiatric conditions, but there has been less attention to this in clinical practice for psychiatrists in training. This review examines the outcomes of communication skills training interventions in psychiatric specialty training. The published English-language literature was examined using multiple online databases, grey literature and hand searches. The review was conducted and reported using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies examining the efficacy of communication skills training were included. Randomised controlled trials, pseudo-randomised studies and quasi-experimental studies, as well as observational analytical studies and qualitative studies that met criteria, were selected and critically appraised. No limits were applied for date of publication up until 16 July 2016. Total search results yielded 2574 records. Of these, 12 studies were identified and reviewed. Two were randomised controlled trials and the remaining 10 were one-group pretest/posttest designs or posttest-only designs, including self-report evaluations of communication skills training and objective evaluations of trainee skills. There were no studies with outcomes related to behaviour change or patient outcomes. Two randomised controlled trials reported an improvement in clinician empathy and psychotherapeutic interviewing skills due to specific training protocols focused on those areas. Non-randomised studies showed varying levels of skills gains and self-reported trainee satisfaction ratings with programmes, with the intervention being some form of communication skills training. The heterogeneity of communication skills training is a barrier to evaluating the efficacy of different communication skills training programmes. Further validation studies examining specific models and frameworks would support a stronger evidence base for communication skills training in psychiatry. It remains a challenge to develop research to investigate behaviour change over time in clinical practice or to measure patient outcomes due to the effects of communication skills training.

Effects of Hibiscus sabdariffa L. on serum lipids: a systematic review and meta-analysis.

PubMed

Aziz, Zoriah; Wong, Su Yuen; Chong, Nyuk Jet

2013-11-25

Prevention of cardiovascular disease by modifying its major risk factors, including serum cholesterol levels, is an important strategy. Hibiscus sabdariffa L. has been promoted for reducing cholesterol levels, but its reported impact on cholesterol levels has been inconsistent. The study aimed to assess systematically the evidence and quality of current research on the effect of Hibiscus sabdariffa L. on blood lipids and its adverse effects. Electronic databases were searched up to June 2013 for relevant randomised controlled trials (RCTs). Journals and conference proceedings were also searched. The quality of the selected trials was assessed using the Cochrane Risk of Bias Assessment Tool. The efficacy results of similar studies were pooled if they used the same comparator. Outcomes examined were levels of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. Six studies involving 474 subjects met our inclusion criteria. These studies varied in terms of the types of interventions, comparators used, and duration of trials. Overall, Hibiscus sabdariffa L. did not produce any significant effect on any of the outcomes examined, when compared with placebo, black tea or diet. With short-term use it is well tolerated. The available evidence from RCTs does not support the efficacy of Hibiscus sabdariffa L. in lowering serum lipids. Further rigorously designed trials with larger sample sizes are warranted to confirm the effects of HS on serum lipids. © 2013 Elsevier Ireland Ltd. All rights reserved.

A tutorial on pilot studies: the what, why and how

PubMed Central

2010-01-01

Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format. PMID:20053272

Risk of bias and methodological issues in randomised controlled trials of acupuncture for knee osteoarthritis: a cross-sectional study

PubMed Central

Lee, Andy H; Zhou, Xu; Kang, Deying; Luo, Yanan; Liu, Jiali; Sun, Xin

2018-01-01

Objective To assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA). Methods PubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators. Results A total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome. Conclusion The overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA. PMID:29511016

Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy

PubMed Central

Brophy, Sinead; Burrows, Claire L; Brooks, Caroline; Gravenor, Michael B; Siebert, Stefan; Allen, Stephen J

2008-01-01

Background The clinical effectiveness of complementary and alternative medicines (CAMs) is widely debated because of a lack of clinical trials. The internet may provide an effective and economical approach for undertaking randomised controlled trials (RCTs) of low-risk interventions. We investigated whether the internet could be used to perform an internet-based RCT of a CAM fulfilling the revised CONSORT (Consolidated Standards of Reporting Trials) statement quality checklist for reporting of RCTs. A secondary aim was to examine the effect of probiotics compared to placebo in terms of well-being over 12 weeks. Methods People aged ≥18 years with confirmed spondyloarthropathy living in the United Kingdom with internet access were invited to participate in an internet-based RCT of probiotic compared to placebo for improving well-being and bowel symptoms. The intervention was a probiotic containing 4 strains of live bacteria or identical placebo taken by mouth daily for 3 months. The primary outcome measure was the performance of the trial according to the revised CONSORT statement. Results 147 people were randomised into the trial. The internet-based trial of the CAM fulfilled the revised CONSORT statement such as efficient blinding, allocation concealment, intention to treat analysis and flow of participants through the trial. Recruitment of the required number of participants was completed in 19 months. Sixty-five percent (96/147) completed the entire 3 months of the trial. The trial was low cost and demonstrated that in an intention to treat analysis, probiotics did not improve well-being or bowel symptoms. Conclusion The internet-based RCT proved to be a successful and economical method for examining this CAM intervention. Recruitment, adherence and completion rate were all similar to those reported with conventional RCTs but at a fraction of the cost. Internet-based RCTs can fulfil all the criteria of the revised CONSORT statement and are an appropriate method for studying low-risk interventions. Trial registration ISRCTN36133252 PMID:18190710

"...because I am something special" or "I think I will be something like a guinea pig": information and assent of legal minors in clinical trials – assessment of understanding, appreciation and reasoning

PubMed Central

Koelch, Michael; Singer, Hanneke; Prestel, Anja; Burkert, Jessica; Schulze, Ulrike; Fegert, Jörg M

2009-01-01

Background The aim of this study is to assess and evaluate the capacities for understanding, appreciation and reasoning of legal minors with psychiatric disorders and their parents and their competence to consent or assent to participation in clinical trials. The beliefs, fears, motivation and influencing factors for decision-making of legal minors and parents were also examined. Methods Using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), an instrument developed for adults whose capacities to consent are unclear, we provided information about clinical trials and assessed understanding, appreciation and reasoning. We adapted this tool for legal minors and examined 19 children and adolescents between the ages of 7 and 15 with attention deficit/hyperactivity disorder (ADHD) or ADHD combined with oppositional defiant disorder (DSM-IV 314.00/314.01/312.8) enrolled in clinical trials. Parents were also examined using the MacCAT-CR. Results Facts such as the procedures involved in trials or their duration were well understood by legal minors, but more abstract issues like the primary purpose of the trial were not understood by children and adolescents or by many parents. Legal minors also had difficulties understanding the nature of placebo and the probability of receiving placebo. Children's and adolescents' decisions were influenced by fears about their disorder worsening and by problems in their relationship with their parents. Parents wanted the best therapy for their children in order to minimize problems in school. Conclusion Legal minors and parents need to be informed more precisely about specific issues like placebo and the primary purpose of trials. In general, the reasoning of children and adolescents was influenced by their experience with their disorder and decision making was based on reasonable arguments. Their fears were based on everyday experiences such as school performance or family relationships. PMID:19175905

Does recruitment source moderate treatment effectiveness? A subgroup analysis from the EVIDENT study, a randomised controlled trial of an internet intervention for depressive symptoms

PubMed Central

Gamon, Carla; Späth, Christina; Berger, Thomas; Meyer, Björn; Hohagen, Fritz; Hautzinger, Martin; Lutz, Wolfgang; Vettorazzi, Eik; Moritz, Steffen; Schröder, Johanna

2017-01-01

Objective This study aims to examine whether the effects of internet interventions for depression generalise to participants recruited in clinical settings. Design This study uses subgroup analysis of the results of a randomised, controlled, single-blind trial. Setting The study takes place in five diagnostic centres in Germany. Participants A total of 1013 people with mild to moderate depressive symptoms were recruited from clinical sources as well as internet forums, statutory insurance companies and other sources. Interventions This study uses either care-as-usual alone (control) or a 12-week internet intervention (Deprexis) plus usual care (intervention). Main outcome measures The primary outcome measure was self-rated depression severity (Patient Health Questionnaire-9) at 3 months and 6 months. Further measures ranged from demographic and clinical parameters to a measure of attitudes towards internet interventions (Attitudes towards Psychological Online Interventions Questionnaire). Results The recruitment source was only associated with very few of the examined demographic and clinical characteristics. Compared with participants recruited from clinical sources, participants recruited through insurance companies were more likely to be employed. Clinically recruited participants were as severely affected as those from other recruitment sources but more sceptical of internet interventions. The effectiveness of the intervention was not differentially associated with recruitment source (treatment by recruitment source interaction=0.28, p=0.84). Conclusion Our results support the hypothesis that the intervention we studied is effective across different recruitment sources including clinical settings. Trial registration number ClinicalTrials.gov NCT01636752. PMID:28710212

Nutrition Education among Low-Income Older Adults: A Randomized Intervention Trial in Congregate Nutrition Sites

ERIC Educational Resources Information Center

Mitchell, Roger E.; Ash, Sarah L.; McClelland, Jacquelyn W.

2006-01-01

Nutritional well-being among older adults is critical for maintaining health, increasing longevity, and decreasing the impact of chronic illness. However, few well-controlled studies have examined nutritional behavior change among low-income older adults. A prospective, controlled, randomized design examined a five session nutrition education…

Examining the Relationship between Family Meal Frequency and Individual Dietary Intake: Does Family Cohesion Play a Role?

ERIC Educational Resources Information Center

Welsh, Ericka M.; French, Simone A.; Wall, Melanie

2011-01-01

Objective: To confirm previously reported associations between family meal frequency and dietary intake, and to examine family cohesion as a potential mediator of this relationship. Design: Cross-sectional observational study. Data collected at baseline via questionnaire. Setting: Randomized, controlled household weight gain prevention trial.…

Object Representation in Infants' Coordination of Manipulative Force

ERIC Educational Resources Information Center

Mash, Clay

2007-01-01

This study examined infants' use of object knowledge for scaling the manipulative force of object-directed actions. Infants 9, 12, and 15 months of age were outfitted with motion-analysis sensors on their arms and then presented with stimulus objects to examine individually over a series of familiarization trials. Two stimulus objects were used in…

Examining the Sustainability of an Evidence-Based Preschool Curriculum: The REDI Program

ERIC Educational Resources Information Center

Sanford DeRousie, Rebecca M.; Bierman, Karen L.

2012-01-01

This study examined the extent to which an evidence-based preschool curriculum (Head Start REDI) was sustained by 20 teachers during the year following a randomized controlled efficacy trial, when teachers were no longer required by the research project to implement the curriculum. Two quantitative measures of sustainability (teacher ratings, REDI…

The Role of Executive Functions for Dyadic Literacy Learning in Kindergarten

ERIC Educational Resources Information Center

van de Sande, Eva; Segers, Eliane; Verhoeven, Ludo

2018-01-01

The current study used a dyadic and coconstructive approach to examine how to embed exercises that support executive functioning into early literacy instruction to empower its effects. Using a randomized controlled trial design with 100 children, we examined the effects of dyadic activities in which children scaffolded each other's learning and…

The Number of Trials Required to Obtain a Representative Movement Pattern During a Hurdle Hop Exercise.

PubMed

Gore, Shane J; Marshall, Brendan M; Franklyn-Miller, Andrew D; Falvey, Eanna C; Moran, Kieran A

2016-06-01

When reporting a subject's mean movement pattern, it is important to ensure that reported values are representative of the subject's typical movement. While previous studies have used the mean of 3 trials, scientific justification of this number is lacking. One approach is to determine statistically how many trials are required to achieve a representative mean. This study compared 4 methods of calculating the number of trials required in a hopping movement to achieve a representative mean. Fifteen males completed 15 trials of a lateral hurdle hop. Range of motion at the trunk, pelvis, hip, knee, and ankle, in addition to peak moments for the latter 3 joints were examined. The number of trials required was computed using a peak intraclass correlation coefficient method, sequential analysis with a bandwidth of acceptable variance in the mean, and a novel method based on the standard error of measurement (SEMind). The number of trials required across all variables ranged from 2 to 12 depending on method, joint, and anatomical plane. The authors advocate the SEMind method as it demonstrated fewer limitations than the other methods. Using the SEMind, the required number of trials for a representative mean during the lateral hurdle hop is 6.

Can lifestyle modification improve neurocognition? Rationale and design of the ENLIGHTEN clinical trial.

PubMed

Blumenthal, James A; Smith, Patrick J; Welsh-Bohmer, Kathleen; Babyak, Michael A; Browndyke, Jeffrey; Lin, Pao-Hwa; Doraiswamy, P Murali; Burke, James; Kraus, William; Hinderliter, Alan; Sherwood, Andrew

2013-01-01

Risk factors for cardiovascular disease (CVD) not only increase the risk for clinical CVD events, but also are associated with a cascade of neurophysiologic and neuroanatomic changes that increase the risk of cognitive impairment and dementia. Although epidemiological studies have shown that exercise and diet are associated with lower CVD risk and reduced incidence of dementia, no randomized controlled trial (RCT) has examined the independent effects of exercise and diet on neurocognitive function among individuals at risk for dementia. The ENLIGHTEN trial is a RCT of patients with CVD risk factors who also are characterized by subjective cognitive complaints and objective evidence of neurocognitive impairment without dementia (CIND) STUDY DESIGN: A 2 by 2 design will examine the independent and combined effects of diet and exercise on neurocognition. 160 participants diagnosed with CIND will be randomly assigned to 6 months of aerobic exercise, the DASH diet, or a combination of both exercise and diet; a (control) group will receive health education but otherwise will maintain their usual dietary and activity habits. Participants will complete comprehensive assessments of neurocognitive functioning along with biomarkers of CVD risk including measures of blood pressure, glucose, endothelial function, and arterial stiffness. The ENLIGHTEN trial will (a) evaluate the effectiveness of aerobic exercise and the DASH diet in improving neurocognitive functioning in CIND patients with CVD risk factors; (b) examine possible mechanisms by which exercise and diet improve neurocognition; and (c) consider potential moderators of treatment, including subclinical CVD. Copyright © 2012 Elsevier Inc. All rights reserved.

Factors affecting recruitment into depression trials: Systematic review, meta-synthesis and conceptual framework.

PubMed

Hughes-Morley, Adwoa; Young, Bridget; Waheed, Waquas; Small, Nicola; Bower, Peter

2015-02-01

Depression is common and clinical trials are crucial for evaluating treatments. Difficulties in recruiting participants into depression trials are well-documented, yet no study has examined the factors affecting recruitment. This review aims to identify the factors affecting recruitment into depression trials and to develop a conceptual framework through systematic assessment of published qualitative research. Systematic review and meta-synthesis of published qualitative studies. Meta-synthesis involves a synthesis of themes across a number of qualitative studies to produce findings that are "greater than the sum of the parts". ASSIA, CINAHL, Embase, Medline and PsychInfo were searched up to April 2013. Reference lists of included studies, key publications and relevant reviews were also searched. Quality appraisal adopted the "prompts for appraising qualitative research". 7977 citations were identified, and 15 studies were included. Findings indicate that the decision to enter a depression trial is made by patients and gatekeepers based on the patient׳s health state at the time of being approached to participate; on their attitude towards the research and trial interventions; and on the extent to which patients become engaged with the trial. Our conceptual framework highlights that the decision to participate by both the patient and the gatekeeper involves a judgement between risk and reward. Only English language publications were included in this review. Findings from this review have implications for the design of interventions to improve recruitment into depression trials. Such interventions may aim to diminish the perceived risks and increase the perceived rewards of participation. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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

A protocol for the delivery of cannabidiol (CBD) and combined CBD and ∆9-tetrahydrocannabinol (THC) by vaporisation

PubMed Central

2014-01-01

Background Significant interest has emerged in the therapeutic and interactive effects of different cannabinoids. Cannabidiol (CBD) has been shown to have anxiolytic and antipsychotic effects with high doses administered orally. We report a series of studies conducted to determine the vaporisation efficiency of high doses of CBD, alone and in combination with ∆9-tetrahydrocannabinol (THC), to achieve faster onset effects in experimental and clinical trials and emulate smoked cannabis. Methods Purified THC and CBD (40 mg/ml and 100 mg/ml respectively) were loaded onto a liquid absorbing pad in a Volcano® vaporiser, vaporised and the vapours quantitatively analysed. Preliminary studies determined 200 mg CBD to be the highest dose effectively vaporised at 230°C, yielding an availability of approximately 40% in the vapour phase. Six confirmatory studies examined the quantity of each compound delivered when 200 mg or 4 mg CBD was loaded together with 8 mg of THC. Results THC showed 55% availability when vaporised alone or with low dose CBD, while large variation in the availability of high dose CBD impacted upon the availability of THC when co-administered, with each compound affecting the vaporisation efficiency of the other in a dynamic and dose-dependent manner. We describe optimised protocols that enable delivery of 160 mg CBD through vaporisation. Conclusions While THC administration by vaporisation is increasingly adopted in experimental studies, often with oral predosing with CBD to examine interactive effects, no studies to date have reported the administration of CBD by vaporisation. We report the detailed methodology aimed at optimising the efficiency of delivery of therapeutic doses of CBD, alone and in combination with THC, by vaporisation. These protocols provide a technical advance that may inform methodology for clinical trials in humans, especially for examining interactions between THC and CBD and for therapeutic applications of CBD. Trial registration Current Controlled Trials ISRCTN24109245 PMID:25319497

Impact of food supplementation on weight loss in randomised-controlled dietary intervention trials: a systematic review and meta-analysis.

PubMed

Wibisono, Cinthya; Probst, Yasmine; Neale, Elizabeth; Tapsell, Linda

2016-04-01

Dietary trials provide evidence for practice and policy guidelines, but poor adherence may confound results. Food supplementation may improve adherence to dietary interventions, but the impact of supplementation on study outcomes is not known. The aim of this review was to examine the impact of food supplementation on weight loss in dietary intervention trials. The databases Scopus, PubMed and the Cochrane Library were searched for dietary intervention trials published between January 2004 and March 2015 using the following keyword combinations: 'trial' OR 'intervention', 'food' OR 'diet', 'weight loss' and 'adherence' OR 'adherence'. Studies were included if food was provided to at least one study group and both 'weight change' and 'adherence' were reported. Random effects meta-analyses were conducted to assess weighted mean differences (WMD) in body weight (change or final mean values). The included studies formed two groups: trials involving an intervention group supplemented with a food and a control without food supplementation (food v. no food), and trials in which food was provided to all subjects (food v. food) (PROSPERO registration: CRD42015017563). In total, sixteen studies were included. Significant weight reduction was reported in the food v. no food studies (WMD -0·74 kg; 95 % CI -1·40, -0·08; P=0·03, I 2=63 %). A non-significant increase in weight was found among the food v. food studies (WMD 0·84 kg; 95 % CI -0·60, 2·27; P=0·25, I 2=0 %). Food supplementation appeared to result in greater weight loss in dietary trials. Energy restrictions and intensity of interventions were other significant factors influencing weight loss.

Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials.

PubMed

Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2016-04-01

We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials. We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation. We examined 13 single-agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and-maintenance (RR = 0.6, 95% CI 0.4-1.0) trials. Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

PubMed

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-12-21

Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

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.

Effects of Study Design and Allocation on participant behaviour--ESDA: study protocol for a randomized controlled trial.

PubMed

Kypri, Kypros; McCambridge, Jim; Wilson, Amanda; Attia, John; Sheeran, Paschal; Bowe, Steve; Vater, Tina

2011-02-14

What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000846022.

Evaluation of mindfulness-based cognitive therapy for life and a cognitive behavioural therapy stress-management workshop to improve healthcare staff stress: study protocol for two randomised controlled trials.

PubMed

Strauss, Clara; Gu, Jenny; Pitman, Nikki; Chapman, Cavita; Kuyken, Willem; Whittington, Adrian

2018-04-02

Healthcare workers experience higher levels of work-related stress and higher rates of sickness absence than workers in other sectors. Psychological approaches have potential in providing healthcare workers with the knowledge and skills to recognise stress and to manage stress effectively. The strongest evidence for effectiveness in reducing stress in the workplace is for stress-management courses based on cognitive behavioural therapy (CBT) principles and mindfulness-based interventions (MBIs). However, research examining effects of these interventions on sickness absence (an objective indicator of stress) and compassion for others (an indicator of patient care) is limited, as is research on brief CBT stress-management courses (which may be more widely accessible) and on MBIs adapted for workplace settings. This protocol is for two randomised controlled trials with participant preference between the two trials and 1:1 allocation to intervention or wait-list within the preferred choice. The first trial is examining a one-day CBT stress-management workshop and the second trial an 8-session Mindfulness-Based Cognitive Therapy for Life (MBCT-L) course, with both trials comparing intervention to wait-list. The primary outcome for both trials is stress post-intervention with secondary outcomes being sickness absence, compassion for others, depression symptoms, anxiety symptoms, wellbeing, work-related burnout, self-compassion, presenteeism, and mindfulness (MBCT-L only). Both trials aim to recruit 234 staff working in the National Health Service in the UK. This trial will examine whether a one-day CBT stress-management workshop and an 8-session MBCT-L course are effective at reducing healthcare staff stress and other mental health outcomes compared to wait-list, and, whether these interventions are effective at reducing sickness absence and presenteeism and at enhancing wellbeing, self-compassion, mindfulness and compassion for others. Findings will help inform approaches offered to reduce healthcare staff stress and other key variables. A note of caution is that individual-level approaches should only be part of the solution to reducing healthcare staff stress within a broader focus on organisational-level interventions and support. ISRCTN Registry, ISRCTN11723441 . Registered on 16 June 2017. Protocol Version 1: 24 April 2017. Trial Sponsor: Sussex Partnership NHS Foundation Trust (ResearchGovernance@sussexpartnership.nhs.uk).

Yogurt and weight management.

PubMed

Jacques, Paul F; Wang, Huifen

2014-05-01

A large body of observational studies and randomized controlled trials (RCTs) has examined the role of dairy products in weight loss and maintenance of healthy weight. Yogurt is a dairy product that is generally very similar to milk, but it also has some unique properties that may enhance its possible role in weight maintenance. This review summarizes the human RCT and prospective observational evidence on the relation of yogurt consumption to the management and maintenance of body weight and composition. The RCT evidence is limited to 2 small, short-term, energy-restricted trials. They both showed greater weight losses with yogurt interventions, but the difference between the yogurt intervention and the control diet was only significant in one of these trials. There are 5 prospective observational studies that have examined the association between yogurt and weight gain. The results of these studies are equivocal. Two of these studies reported that individuals with higher yogurt consumption gained less weight over time. One of these same studies also considered changes in waist circumference (WC) and showed that higher yogurt consumption was associated with smaller increases in WC. A third study was inconclusive because of low statistical power. A fourth study observed no association between changes in yogurt intake and weight gain, but the results suggested that those with the largest increases in yogurt intake during the study also had the highest increase in WC. The final study examined weight and WC change separately by sex and baseline weight status and showed benefits for both weight and WC changes for higher yogurt consumption in overweight men, but it also found that higher yogurt consumption in normal-weight women was associated with a greater increase in weight over follow-up. Potential underlying mechanisms for the action of yogurt on weight are briefly discussed.

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

PubMed

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

2017-03-22

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

Adherence in single-parent households in a long-term asthma clinical trial.

PubMed

Spicher, Mary; Bollers, Nancy; Chinn, Tamara; Hall, Anita; Plunkett, Anne; Rodgers, Denise; Sundström, D A; Wilson, Laura

2012-01-01

Adherence of participants in a long-term clinical trial is necessary to assure validity of findings. This article examines adherence differences between single-parent and two-parent families in the Childhood Asthma Management Program (CAMP). Adherence was defined as the percentage of completed daily diary cards and scheduled study visits during the course of the trial. Logistic regression and ordinal logistic regression analyses were used. Children from single-parent families had a lower percentage of completed diary cards (72% vs. 84%) than two-parent families. Single-parent families were also more likely to reschedule visits (62% vs. 45%) and miss more clinic visits (23% vs. 17%) than two-parent families. Suggestions are given for study coordinators to assist participants in completing a long-term clinical trial. Many suggestions may be adapted for nurses in inpatient or outpatient settings for assisting parents of patients with chronic diseases.

Introduction to the Special Series: Current Directions for Measuring Parenting Constructs to Inform Prevention Science.

PubMed

Lindhiem, Oliver; Shaffer, Anne

2017-04-01

Parenting behaviors are multifaceted and dynamic and therefore challenging to quantify. Measurement methods have critical implications for study results, particularly for prevention trials designed to modify parenting behaviors. Although multiple approaches can complement one another and contribute to a more complete understanding of prevention trials, the assumptions and implications of each approach are not always clearly addressed. Greater attention to the measurement of complex constructs such as parenting is needed to advance the field of prevention science. This series examines the challenges of measuring changes in parenting behaviors in the context of prevention trials. All manuscripts in the special series address measurement issues and make practical recommendations for prevention researchers. Manuscripts in this special series include (1) empirical studies that demonstrate novel measurement approaches, (2) re-analyses of prevention trial outcome data directly comparing and contrasting two or more methods, and (3) a statistical primer and practical guide to analyzing proportion data.

[A study of the transport of three dimensional medical images to remote institutions for telediagnosis].

PubMed

Hayashi, Takashi; Iwai, Mitsuhiro; Takahashi, Katsuhiko; Takeda, Satoshi; Tateishi, Toshiki; Kaneko, Rumi; Ogasawara, Yoko; Yonezawa, Kazuya; Hanada, Akiko

2011-01-01

Using a 3D-imaging-create-function server and network services by IP-VPN, we began to deliver 3D images to the remote institution. An indication trial of the primary image, a rotary trial of a 3D image, and a reproducibility trial were studied in order to examine the practicality of using the system in a real network between Hakodate and Sapporo (communication distance of about 150 km). In these trials, basic data (time and receiving data volume) were measured for every variation of QF (quality factor) or monitor resolution. Analyzing the results of the system using a 3D image delivery server of our hospital with variations in the setting of QF and monitor resolutions, we concluded that this system has practicality in the remote interpretation-of-radiogram work, even if the access point of the region has a line speed of 6 Mbps.

The reliability of a VISION COACH task as a measure of psychomotor skills.

PubMed

Xi, Yubin; Rosopa, Patrick J; Mossey, Mary; Crisler, Matthew C; Drouin, Nathalie; Kopera, Kevin; Brooks, Johnell O

2014-10-01

The VISION COACH™ interactive light board is designed to test and enhance participants' psychomotor skills. The primary goal of this study was to examine the test-retest reliability of the Full Field 120 VISION COACH task. One hundred eleven male and 131 female adult participants completed six trials where they responded to 120 randomly distributed lights displayed on the VISION COACH interactive light board. The mean time required for a participant to complete a trial was 101 seconds. Intraclass correlation coefficients, ranging from 0.962 to 0.987 suggest the VISION COACH Full Field 120 task was a reliable task. Cohen's d's of adjacent pairs of trials suggest learning effects did not negatively affect reliability after the third trial.

Challenges and opportunities in SLE clinical trials.

PubMed

van Vollenhoven, Ronald F

2013-09-01

To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward. Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results. An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.

Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

PubMed

Mansour, J K; Beaudry, J L; Lindsay, R C L

2017-12-01

Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

How Can the Evidence from Global Large-scale Clinical Trials for Cardiovascular Diseases be Improved?

PubMed

Sawata, Hiroshi; Tsutani, Kiichiro

2011-06-29

Clinical investigations are important for obtaining evidence to improve medical treatment. Large-scale clinical trials with thousands of participants are particularly important for this purpose in cardiovascular diseases. Conducting large-scale clinical trials entails high research costs. This study sought to investigate global trends in large-scale clinical trials in cardiovascular diseases. We searched for trials using clinicaltrials.gov (URL: http://www.clinicaltrials.gov/) using the key words 'cardio' and 'event' in all fields on 10 April, 2010. We then selected trials with 300 or more participants examining cardiovascular diseases. The search revealed 344 trials that met our criteria. Of 344 trials, 71% were randomized controlled trials, 15% involved more than 10,000 participants, and 59% were funded by industry. In RCTs whose results were disclosed, 55% of industry-funded trials and 25% of non-industry funded trials reported statistically significant superiority over control (p = 0.012, 2-sided Fisher's exact test). Our findings highlighted concerns regarding potential bias related to funding sources, and that researchers should be aware of the importance of trial information disclosures and conflicts of interest. We should keep considering management and training regarding information disclosures and conflicts of interest for researchers. This could lead to better clinical evidence and further improvements in the development of medical treatment worldwide.

Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

PubMed

Ourso, André

2012-01-01

Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.

PubMed

Shang, Aijing; Huwiler-Müntener, Karin; Nartey, Linda; Jüni, Peter; Dörig, Stephan; Sterne, Jonathan A C; Pewsner, Daniel; Egger, Matthias

Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias. Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models. 110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials). Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

Patient preferences and performance bias in a weight loss trial with a usual care arm☆☆☆

PubMed Central

McCambridge, Jim; Sorhaindo, Annik; Quirk, Alan; Nanchahal, Kiran

2014-01-01

Objectives This qualitative study examines performance bias, i.e. unintended differences between groups, in the context of a weight loss trial in which a novel patient counseling program was compared to usual care in general practice. Methods 14/381 consecutive interviewees (6 intervention group, 8 control group) within the CAMWEL (Camden Weight Loss) effectiveness trial process study were asked about their engagement with various features of the research study and a thematic content analysis undertaken. Results Decisions to participate were interwoven with decisions to change behavior, to the extent that for many participants the two were synonymous. The intervention group were satisfied with their allocation. The control group spoke of their disappointment at having been offered usual care when they had taken part in the trial to access new forms of help. Reactions to disappointment involved both movements toward and away from behavior change. Conclusion There is a prima facie case that reactions to disappointment may introduce bias, as they lead the randomized groups to differ in ways other than the intended experimental contrast. Practice implications In-depth qualitative studies nested within trials are needed to understand better the processes through which bias may be introduced. PMID:24492159

Mind-body Therapies for Menopausal Symptoms: A Systematic Review

PubMed Central

Innes, Kim E; Selfe, Terry Kit; Vishnu, Abhishek

2010-01-01

Objective To systematically review the peer-reviewed literature regarding the effects of self-administered mind-body therapies on menopausal symptoms. Methods To identify qualifying studies, we searched 10 scientific databases and scanned bibliographies of relevant review papers and all identified articles. The methodological quality of all studies was assessed systematically using predefined criteria. Results Twenty-one papers representing 18 clinical trials from 6 countries met our inclusion criteria, including 12 randomized controlled trials (N=719), 1 non-randomized controlled trial (N=58), and 5 uncontrolled trials (N=105). Interventions included yoga and/or meditation-based programs, tai chi, and other relaxation practices, including muscle relaxation and breath-based techniques, relaxation response training, and low frequency sound-wave therapy. Eight of the nine studies of yoga, tai chi, and meditation-based programs reported improvement in overall menopausal and vasomotor symptoms; six of seven trials indicated improvement in mood and sleep with yoga-based programs, and four studies reported reduced musculoskeletal pain. Results from the remaining nine trials suggest that breath-based and other relaxation therapies also show promise for alleviating vasomotor and other menopausal symptoms, although intergroup findings were mixed. Most studies reviewed suffered methodological or other limitations, complicating interpretation of findings. Conclusions Collectively, findings of these studies suggest that yoga-based and certain other mind-body therapies may be beneficial for alleviating specific menopausal symptoms. However, the limitations characterizing most studies hinder interpretation of findings and preclude firm conclusions regarding efficacy. Additional large, methodologically sound trials are needed to determine the effects of specific mind-body therapies on menopausal symptoms, examine long-term outcomes, and investigate underlying mechanisms. PMID:20167444

Attentional bias for emotional faces in paediatric anxiety disorders: an investigation using the emotional Go/No Go task.

PubMed

Waters, Allison M; Valvoi, Jaya S

2009-06-01

The present study examined contextual modulation of attentional control processes in paediatric anxiety disorders. Anxious children (N=20) and non-anxious controls (N=20) completed an emotional Go/No Go task in which they responded on some trials (i.e., Go trials) when neutral faces were presented amongst either angry or happy faces to which children avoided responding (i.e., No Go trials) or when angry and happy faces were presented as Go trials and children avoided responding to neutral faces. Anxious girls were slower responding to neutral faces with embedded angry compared with happy face No Go trials whereas non-anxious girls were slower responding to neutral faces with embedded happy versus angry face No Go trials. Anxious and non-anxious boys showed the same basic pattern as non-anxious girls. There were no significant group differences on No Go trials or when the emotional faces were presented as Go trials. Results are discussed in terms of selective interference by angry faces in the control of attention in anxious girls.

Effects of yoga on chronic neck pain: a systematic review of randomized controlled trials

PubMed Central

Kim, Sang-Dol

2016-01-01

[Purpose] The aim of this study was to investigate the effectiveness of yoga in the management of chronic neck pain. [Subjects and Methods] Five electronic databases were searched to identify randomized controlled trials (RCTs) of yoga intervention on chronic neck pain. The trials were published in the English language between January 1966 and December 2015. The Cochrane Risk of Bias Tool was used to assess the quality of the trials. [Results] Three trials were identified and included in this review. A critical appraisal was performed on the trials, and the result indicated a high risk of bias. A narrative description was processed because of the small number of RCTs. Neck pain intensity and functional disability were significantly lower in the yoga groups than in the control groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that yoga may be beneficial for chronic neck pain. The low-quality result of the critical appraisal and the small number of trials suggest that high-quality RCTs are required to examine further the effects of yoga intervention on chronic neck pain relief. PMID:27512290

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by pharmaceutical companies. The findings suggest that ethical and scientific issues related to choice of control group in psoriasis trials are interpreted markedly differently depending on trial location and funding source.

Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov.

PubMed

Ruopp, Marcus; Chiswell, Karen; Thaden, Joshua T; Merchant, Kunal; Tsalik, Ephraim L

2015-12-01

Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance. We analyzed data from ClinicalTrials.gov to summarize activity in respiratory infection trials, identify gaps in research activity, and inform efforts to address disparities between antimicrobial resistance and development of new antibacterial drugs. We examined 69,779 interventional trials registered with ClinicalTrials.gov from 2007 to 2012, focusing on study conditions and interventions to identify respiratory infection-related trials. Programmatic identification with manual confirmation yielded 6,253 infectious disease trials, 1,377 respiratory infection trials, and 270 lower respiratory tract infection trials for analysis. The 1,377 respiratory infection trials accounted for 2% of all trials and 22% of infectious diseases trials. Such trials (54.8%) were more likely than either nonrespiratory infectious diseases trials (48.1%) or noninfectious disease trials (42.8%) to receive industry funding. Stratification of respiratory infection trials by registration year demonstrated declining industry funding: 181 (64.9%) in 2007-2008 to 110 (46.0%) in 2011-2012. Respiratory infection trials more frequently evaluated vaccines (52.7 vs. 15.5% of nonrespiratory tract infection trials). Lower respiratory tract infection trials (excluding tuberculosis) focused primarily on bacterial pathogens (78.5%) followed by viral (12.6%), fungal (5.6%), and nontuberculous mycobacterial (3.0%) pathogens. Approximately 40% of 120 lower respiratory tract infection trials that were completed or terminated published results in the literature. On multivariable logistic regression analysis, a treatment focus was associated with decreased odds of publishing results (odds ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.02). There were also generally low numbers of studies evaluating novel antimicrobial agents (community-acquired pneumonia, 15.9%; hospital-acquired pneumonia, 16.7%; ventilator-associated pneumonia, 5.3%). From 2007 to 2012, respiratory infection trials did not occur in numbers commensurate with global impact. The number of trials registered per year did not increase throughout the study period, partly due to declining industry support. There was a concerning reduction in prevention-oriented lower respiratory infection trials and an overall low number of such trials involving novel antimicrobials.

Lung-MAP Clinical Trial

Cancer.gov

A collection of material about the Lung-MAP study, which will examine treatment outcomes for patients with squamous cell lung cancer assigned to different targeted drugs based on the results of genomic tumor profiling.

Combined hormonal versus nonhormonal versus progestin-only contraception in lactation.

PubMed

Lopez, Laureen M; Grey, Thomas W; Stuebe, Alison M; Chen, Mario; Truitt, Sarah T; Gallo, Maria F

2015-03-20

Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant. Ideally, the contraceptive chosen should not interfere with lactation or infant growth. Timing of contraception initiation is also important. Immediately postpartum, most women have contact with a health professional, but many do not return for follow-up contraceptive counseling. However, immediate initiation of hormonal methods may disrupt the onset of milk production. To determine the effects of hormonal contraceptives on lactation and infant growth We searched for eligible trials until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov, and ICTRP. We also examined review articles and contacted investigators. We sought randomized controlled trials in any language that compared hormonal contraception versus another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception includes combined or progestin-only oral contraceptives, injectable contraceptives, implants, and intrauterine devices.Trials had to have one of our primary outcomes: breast milk quantity or biochemical composition; lactation initiation, maintenance, or duration; infant growth; or timing of contraception initiation and effect on lactation. Secondary outcomes included contraceptive efficacy while breastfeeding and birth interval. For continuous variables, we calculated the mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% CI. Due to differing interventions and outcome measures, we did not aggregate the data in a meta-analysis. In 2014, we added seven trials for a new total of 11. Five reports were published before 1985 and six from 2005 to 2014. They included 1482 women. Four trials examined combined oral contraceptives (COCs), and three studied a levonorgestrel-releasing intrauterine system (LNG-IUS). We found two trials of progestin-only pills (POPs) and two of the etonogestrel-releasing implant. Older studies often lacked quantified results. Most trials did not report significant differences between the study arms in breastfeeding duration, breast milk composition, or infant growth. Exceptions were seen mainly in older studies with limited information.For breastfeeding duration, two of eight trials indicated a negative effect on lactation. A COC study reported a negative effect on lactation duration compared to placebo but did not quantify results. Another trial showed a lower percentage of the LNG-IUS group breastfeeding at 75 days versus the nonhormonal IUD group (reported P < 0.05) but no significant difference at one year.For breast milk volume, two older studies indicated lower volume for the COC group versus the placebo group. One trial did not quantify results. The other showed lower means (mL) for the COC group, e.g. at 16 weeks (MD -24.00, 95% CI -34.53 to -13.47) and at 24 weeks (MD -24.90, 95% CI -36.01 to -13.79). Another four trials did not report any significant difference between the study groups in milk volume or composition with two POPs, a COC, or the etonogestrel implant.Seven trials studied infant growth; one showed greater weight gain (grams) for the etonogestrel implant versus no method for six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less compared with depot medroxyprogesterone acetate (DMPA) from 6 to 12 weeks (MD -271.00, 95% CI -355.10 to -186.90). The others studied POPs, COCs versus POPs, or an LNG-IUS. Results were not consistent across the 11 trials. The evidence was limited for any particular hormonal method. The quality of evidence was moderate overall and low for three of four placebo-controlled trials of COCs or POPs. The sensitivity analysis included six trials with moderate quality evidence and sufficient outcome data. Five trials indicated no significant difference between groups in breastfeeding duration (etonogestrel implant insertion times, COC versus POP, and LNG-IUS). For breast milk volume or composition, a COC study showed a negative effect, while an implant trial showed no significant difference. Of four trials that assessed infant growth, three indicated no significant difference between groups. One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA.

Effect of tobacco craving cues on memory encoding and retrieval in smokers.

PubMed

Heishman, Stephen J; Boas, Zachary P; Hager, Marguerite C; Taylor, Richard C; Singleton, Edward G; Moolchan, Eric T

2006-07-01

Previous studies have shown that cue-elicited tobacco craving disrupted performance on cognitive tasks; however, no study has examined directly the effect of cue-elicited craving on memory encoding and retrieval. A distinction between encoding and retireval has been reported such that memory is more impaired when attention is divided at encoding than at retrieval. This study tested the hypothesis that active imagery of smoking situations would impair encoding processes, but have little effect on retrieval. Imagery scripts (cigarette craving and neutral content) were presented either before presentation of a word list (encoding trials) or before word recall (retrieval trials). A working memory task at encoding and free recall of words were assessed. Results indicated that active imagery disrupted working memory on encoding trials, but not on retrieval trials. There was a trend toward impaired working memory following craving scripts compared with neutral scripts. These data support the hypothesis that the cognitive underpinnings of encoding and retrieval processes are distinct.

Effects of a Brief Early Start Denver Model (ESDM)-Based Parent Intervention on Toddlers at Risk for Autism Spectrum Disorders: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Rogers, Sally J.; Estes, Annette; Lord, Catherine; Vismara, Laurie; Winter, Jamie; Fitzpatrick, Annette; Guo, Mengye; Dawson, Geraldine

2012-01-01

Objective: This study was carried out to examine the efficacy of a 12-week, low-intensity (1-hour/wk of therapist contact), parent-delivered intervention for toddlers at risk for autism spectrum disorders (ASD) aged 14 to 24 months and their families. Method: A randomized controlled trial involving 98 children and families was carried out in three…

Reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group: A challenge for clinical trial design.

PubMed

Hughes, Michael; Tracey, Andrew; Bhushan, Monica; Chakravarty, Kuntal; Denton, Christopher P; Dubey, Shirish; Guiducci, Serena; Muir, Lindsay; Ong, Voon; Parker, Louise; Pauling, John D; Prabu, Athiveeraramapandian; Rogers, Christine; Roberts, Christopher; Herrick, Ariane L

2018-06-01

The reliability of clinician grading of systemic sclerosis-related digital ulcers has been reported to be poor to moderate at best, which has important implications for clinical trial design. The aim of this study was to examine the reliability of new proposed UK Scleroderma Study Group digital ulcer definitions among UK clinicians with an interest in systemic sclerosis. Raters graded (through a custom-built interface) 90 images (80 unique and 10 repeat) of a range of digital lesions collected from patients with systemic sclerosis. Lesions were graded on an ordinal scale of severity: 'no ulcer', 'healed ulcer' or 'digital ulcer'. A total of 23 clinicians - 18 rheumatologists, 3 dermatologists, 1 hand surgeon and 1 specialist rheumatology nurse - completed the study. A total of 2070 (1840 unique + 230 repeat) image gradings were obtained. For intra-rater reliability, across all images, the overall weighted kappa coefficient was high (0.71) and was moderate (0.55) when averaged across individual raters. Overall inter-rater reliability was poor (0.15). Although our proposed digital ulcer definitions had high intra-rater reliability, the overall inter-rater reliability was poor. Our study highlights the challenges of digital ulcer assessment by clinicians with an interest in systemic sclerosis and provides a number of useful insights for future clinical trial design. Further research is warranted to improve the reliability of digital ulcer definition/rating as an outcome measure in clinical trials, including examining the role for objective measurement techniques, and the development of digital ulcer patient-reported outcome measures.

Crowdsourcing as a screening tool to detect clinical features of glaucomatous optic neuropathy from digital photography.

PubMed

Mitry, Danny; Peto, Tunde; Hayat, Shabina; Blows, Peter; Morgan, James; Khaw, Kay-Tee; Foster, Paul J

2015-01-01

Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images. Optic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83-88% across both trials and study designs, however the specificity was poor, ranging between 35-43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62-0.66) and in trial 2 it was 0.63(0.61-0.65). There were no significant differences between study design or trials conducted. Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.

Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

PubMed Central

Tzoulaki, Ioanna; Zgaga, Lina; Ioannidis, John P A

2014-01-01

Objective To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. Design Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. Data sources Medline, Embase, and screening of citations and references. Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). Results 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. Conclusions Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable. PMID:24690624

Testing moderation in network meta-analysis with individual participant data.

PubMed

Dagne, Getachew A; Brown, C Hendricks; Howe, George; Kellam, Sheppard G; Liu, Lei

2016-07-10

Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Reproducibility of clinical research in critical care: a scoping review.

PubMed

Niven, Daniel J; McCormick, T Jared; Straus, Sharon E; Hemmelgarn, Brenda R; Jeffs, Lianne; Barnes, Tavish R M; Stelfox, Henry T

2018-02-21

The ability to reproduce experiments is a defining principle of science. Reproducibility of clinical research has received relatively little scientific attention. However, it is important as it may inform clinical practice, research agendas, and the design of future studies. We used scoping review methods to examine reproducibility within a cohort of randomized trials examining clinical critical care research and published in the top general medical and critical care journals. To identify relevant clinical practices, we searched the New England Journal of Medicine, The Lancet, and JAMA for randomized trials published up to April 2016. To identify a comprehensive set of studies for these practices, included articles informed secondary searches within other high-impact medical and specialty journals. We included late-phase randomized controlled trials examining therapeutic clinical practices in adults admitted to general medical-surgical or specialty intensive care units (ICUs). Included articles were classified using a reproducibility framework. An original study was the first to evaluate a clinical practice. A reproduction attempt re-evaluated that practice in a new set of participants. Overall, 158 practices were examined in 275 included articles. A reproduction attempt was identified for 66 practices (42%, 95% CI 33-50%). Original studies reported larger effects than reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5% vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with a reproduction attempt demonstrated effects that were inconsistent with the original study (56%, 95% CI 42-68%), among which a large number were reported to be efficacious in the original study and to lack efficacy in the reproduction attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the original study were found to be harmful in the reproduction attempt. A minority of critical care practices with research published in high-profile journals were evaluated for reproducibility; less than half had reproducible effects.

Optimizing adherence in HIV prevention product trials: Development and psychometric evaluation of simple tools for screening and adherence counseling.

PubMed

Tolley, Elizabeth E; Guthrie, Kate Morrow; Zissette, Seth; Fava, Joseph L; Gill, Katherine; Louw, Cheryl E; Kotze, Philip; Reddy, Krishnaveni; MacQueen, Kathleen

2018-01-01

Low adherence in recent HIV prevention clinical trials highlights the need to better understand, measure, and support product use within clinical trials. Conventional self-reported adherence instruments within HIV prevention trials, often relying on single-item questions, have proven ineffective. While objective adherence measures are desirable, none currently exist that apply to both active and placebo arms. Scales are composed of multiple items in the form of questions or statements that, when combined, measure a more complex construct that may not be directly observable. When psychometrically validated, such measures may better assess the multiple factors contributing to adherence/non-adherence. This study aimed to develop and psychometrically evaluate tools to screen and monitor trial participants' adherence to HIV prevention products within the context of clinical trial research. Based on an extensive literature review and conceptual framework, we identified and refined 86 items assessing potential predictors of adherence and 48 items assessing adherence experience. A structured survey, including adherence items and other variables, was administered to former ASPIRE and Ring Study participants and similar non-trial participants (n = 709). We conducted exploratory factor analyses (EFA) to identify a reduced set of constructs and items that could be used at screening to predict potential adherence, and at follow-up to monitor and intervene on adherence. We examined associations with other variables to assess content and construct validity. The EFA of screener items resulted in a 6-factor solution with acceptable to very good internal reliability (α: .62-.84). Similar to our conceptual framework, factors represent trial-related commitment (Distrust of Research and Commitment to Research); alignment with trial requirements (Visit Adherence and Trial Incompatibility); Belief in Trial Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4 Product-specific factors that represent Vaginal Ring Doubts, Vaginal Ring Benefits, Ring Removal, and Side Effects with good to very good internal reliability (α = .71-.82). Evidence of content and construct validity was found; relationship to social desirability bias was examined. These scales are easy and inexpensive to administer, available in several languages, and are applicable regardless of randomization. Once validated prospectively, they could (1) screen for propensity to adhere, (2) target adherence support/counselling, and (3) complement biomarker measures in determining true efficacy of the experimental product.

The Role of Health Care Provider and Partner Decisional Support in Patients' Cancer Treatment Decision-Making Satisfaction.

PubMed

Palmer-Wackerly, Angela L; Krieger, Janice L; Rhodes, Nancy D

2017-01-01

Cancer patients rely on multiple sources of support when making treatment decisions; however, most research studies examine the influence of health care provider support while the influence of family member support is understudied. The current study fills this gap by examining the influence of health care providers and partners on decision-making satisfaction. In a cross-sectional study via an online Qualtrics panel, we surveyed cancer patients who reported that they had a spouse or romantic partner when making cancer treatment decisions (n = 479). Decisional support was measured using 5-point, single-item scales for emotional support, informational support, informational-advice support, and appraisal support. Decision-making satisfaction was measured using Holmes-Rovner and colleagues' (1996) Satisfaction With Decision Scale. We conducted a mediated regression analysis to examine treatment decision-making satisfaction for all participants and a moderated mediation analysis to examine treatment satisfaction among those patients offered a clinical trial. Results indicated that partner support significantly and partially mediated the relationship between health care provider support and patients' decision-making satisfaction but that results did not vary by enrollment in a clinical trial. This study shows how and why decisional support from partners affects communication between health care providers and cancer patients.

Massage, reflexology and other manual methods for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Jones, Leanne

2012-02-15

Many women would like to avoid pharmacological or invasive methods of pain management in labour, and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of manual healing methods including massage and reflexology for pain management in labour. To examine the effects of manual healing methods including massage and reflexology for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 30 June 2011), CINAHL (1980 to 30 June 2011), the Australian and New Zealand Clinical Trial Registry (30 June 2011), Chinese Clinical Trial Register (30 June 2011), Current Controlled Trials (30 June 2011), ClinicalTrials.gov, (30 June 2011) ISRCTN Register (30 June 2011), National Centre for Complementary and Alternative Medicine (NCCAM) (30 June 2011) and the WHO International Clinical Trials Registry Platform (30 June 2011). Randomised controlled trials comparing manual healing methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two authors independently assessed trial quality and extracted data. We attempted to contact study authors for additional information. We included six trials, with data reporting on five trials and 326 women in the meta-analysis. We found trials for massage only. Less pain during labour was reported from massage compared with usual care during the first stage of labour (standardised mean difference (SMD) -0.82, 95% confidence interval (CI) -1.17 to -0.47), four trials, 225 women), and labour pain was reduced in one trial of massage compared with music (risk ratio (RR) 0.40, 95% CI 0.18 to 0.89, 101 women). One trial of massage compared with usual care found reduced anxiety during the first stage of labour (MD -16.27, 95% CI -27.03 to -5.51, 60 women). No trial was assessed as being at a low risk of bias for all quality domains. Massage may have a role in reducing pain, and improving women's emotional experience of labour. However, there is a need for further research.

Reliability of Internet- Versus Telephone-Administered Questionnaires in a Diverse Sample of Smokers

PubMed Central

Papandonatos, George D

2008-01-01

Background Smoking is more prevalent among lower-income individuals and certain racial/ethnic minorities. Addressing tobacco cessation among diverse populations is an urgent public health priority. As Internet use continues to rise among all segments of the US population, Web-based interventions have enormous potential to reach priority populations. Conducting Web-based smoking cessation research in priority populations requires psychometrically sound measurement instruments. To date, only one published study has examined the psychometric properties of Internet-administered measures commonly used in Web-based cessation trials. However, the sample was homogeneous with regard to race/ethnicity and income. We sought to replicate and extend these findings in a more diverse sample of smokers. Objective The aim was to examine the internal consistency and test-retest reliability of measures commonly used in smoking cessation clinical trials among racial/ethnic minorities and smokers with lower income. Methods Participants were enrolled in a randomized trial of the efficacy of an Internet smoking cessation program between June 2005 and September 2006. Following a baseline telephone assessment and randomization into the parent trial, participants were recruited to the reliability substudy. In phase I of recruitment, all participants in the parent trial were recruited to the substudy; in phase II, all consecutive racial/ethnic minority participants in the parent trial were recruited. Race and ethnicity were assessed via self-report using two standard items from the US Office of Management and Budget. An email was sent 2 days after the telephone assessment with a link to the Internet survey. Measures examined were quit methods, perceived stress, depression, social support, smoking temptations, alcohol use, perceived health status, and income. Internal consistency and test-retest reliability of Internet- versus telephone-administered measures were examined within four strata defined by race/ethnicity (non-Hispanic White, racial/ethnic minority) and annual household income (US $40,000 or less, more than $40,000). Results Of the 442 individuals invited, 319 participated (72% response rate): 52.4% were non-Hispanic White, 22.9% Black, 11.6% Hispanic, 7.8% Asian, 4.4% American Indian / Alaska Native, and 1% Native Hawaiian / Other Pacific Islander. About half (49.4%) reported an annual household income of US $40,000 or less, and 25.7% had a high school degree or less. Test-retest reliability was satisfactory to excellent across all strata for the majority of measures examined: 9 of 12 continuous variables had intraclass correlation coefficients ≥ 0.70, and 10 of 18 binary variables and both ordinal variables had kappa coefficients ≥ 0.70. Test-retest reliability of several quit methods varied across strata. Conclusions Race/ethnicity and income do not affect the psychometric properties of most Internet-administered measures examined. This knowledge adds to the confidence of conducting Web-based smoking cessation research and strengthens the scientific rigor of collecting information via the Internet on racial/ethnic minority and low-income subgroups. Trial registration clinicaltrials.gov NCT00282009 (parent trial) PMID:18364345

Study protocol: a randomised controlled trial of cognitive remediation for a national cohort of forensic mental health patients with schizophrenia or schizoaffective disorder.

PubMed

O'Reilly, Ken; Donohoe, Gary; O'Sullivan, Danny; Coyle, Ciaran; Mullaney, Ronan; O'Connell, Paul; Maddock, Catherine; Nulty, Andrea; O'Flynn, Padraic; O'Connell, Carina; Kennedy, Harry G

2016-01-13

Evidence is accumulating that cognitive remediation therapy (CRT) is an effective intervention for patients with schizophrenia or schizoaffective disorder. To date there has been no randomised controlled trial (RCT) cohort study of cognitive remediation within a forensic hospital. The goal of this study is to examine the effectiveness of a trial of cognitive remediation for forensic mental health patients with schizophrenia or schizoaffective disorder. An estimated sixty patients will be enrolled in the study. Participants will be randomised to one of two conditions: CRT with treatment as usual (TAU), or TAU. CRT will consist of 42 individual sessions and 14 group sessions. The primary outcome measure for this study is change in cognitive functioning using the MATRICS Consensus Cognitive Battery (MCCB). Secondary outcomes include change in social and occupational functioning, disorganised symptoms, negative symptoms, violence, participation in psychosocial treatment and recovery. In addition to these effectiveness measures, we will examine patient satisfaction. Cognitive difficulties experienced by schizophrenia spectrum patients are associated with general functioning, ability to benefit from psychosocial interventions and quality of life. Research into the treatment of cognitive difficulties within a forensic setting is therefore an important priority. The results of the proposed study will help answer the question whether cognitive remediation improves functional outcomes in forensic mental health patients with schizophrenia or schizoaffective disorder. Forensic mental health patients are detained for the dual purpose of receiving treatment and for public protection. There can be conflict between these two roles perhaps causing forensic services to have an increased length of stay compared to general psychiatric admissions. Ultimately a focus on emphasising cognition and general functioning over symptoms may decrease tension between the core responsibilities of forensic mental health services. ClinicalTrials.gov Identifier: NCT02360813. Trial registered Feb 4th 2015 and last updated May 1(st) 2015.

Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial.

PubMed

Downer, Mary Kathryn; Gea, Alfredo; Stampfer, Meir; Sánchez-Tainta, Ana; Corella, Dolores; Salas-Salvadó, Jordi; Ros, Emilio; Estruch, Ramón; Fitó, Montserrat; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; De-la-Corte, Francisco Jose Garcia; Serra-Majem, Lluís; Pinto, Xavier; Basora, Josep; Sorlí, José V; Vinyoles, Ernest; Zazpe, Itziar; Martínez-González, Miguel-Ángel

2016-06-14

Dietary intervention success requires strong participant adherence, but very few studies have examined factors related to both short-term and long-term adherence. A better understanding of predictors of adherence is necessary to improve the design and execution of dietary intervention trials. This study was designed to identify participant characteristics at baseline and study features that predict short-term and long-term adherence with interventions promoting the Mediterranean-type diet (MedDiet) in the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial. Analyses included men and women living in Spain aged 55-80 at high risk for cardiovascular disease. Participants were randomized to the MedDiet supplemented with either complementary extra-virgin olive oil (EVOO) or tree nuts. The control group and participants with insufficient information on adherence were excluded. PREDIMED began in 2003 and ended in 2010. Investigators assessed covariates at baseline and dietary information was updated yearly throughout follow-up. Adherence was measured with a validated 14-point Mediterranean-type diet adherence score. Logistic regression was used to examine associations between baseline characteristics and adherence at one and four years of follow-up. Participants were randomized to the MedDiet supplemented with EVOO (n = 2,543; 1,962 after exclusions) or tree nuts (n = 2,454; 2,236 after exclusions). A higher number of cardiovascular risk factors, larger waist circumference, lower physical activity levels, lower total energy intake, poorer baseline adherence to the 14-point adherence score, and allocation to MedDiet + EVOO each independently predicted poorer adherence. Participants from PREDIMED recruiting centers with a higher total workload (measured as total number of persons-years of follow-up) achieved better adherence. No adverse events or side effects were reported. To maximize dietary adherence in dietary interventions, additional efforts to promote adherence should be used for participants with lower baseline adherence to the intended diet and poorer health status. The design of multicenter nutrition trials should prioritize few large centers with more participants in each, rather than many small centers. This study was registered at controlled-trials.com (http://www.controlled-trials. com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005. parallel randomized trial.

The globalization of pediatric clinical trials.

PubMed

Dunne, Julia; Murphy, M Dianne; Rodriguez, William J

2012-12-01

To examine the characteristics of pediatric trials conducted under US legislation and to compare results with data from 2002 to 2007. We reviewed all pediatric trials provided to the US Food and Drug Administration in submissions that were approved between September 28, 2007 and December 21, 2010. We extracted data for each trial including age range, therapeutic indication, design, duration, and patient and center enrollment by location. Overall 346 studies on 113 drugs and biologicals enrolled 55 819 pediatric patients. The United States participated in 86% of the studies, providing 71% of the centers and 74% of the patients. Corresponding percentages for non-US countries were 43%, 29%, and 26% respectively. Developing or transition countries participated in 22% of the studies, providing 12% of the centers and 10% of the patients; our earlier analysis found corresponding percentages of 38%, 12%, and 23%. The most common therapeutic areas studied in the latter countries were infectious, neurologic, and pulmonary diseases. Seventy-eight vaccine studies enrolled 147 692 patients. The United States participated in 40% of the studies, providing 39% of the centers and 22% of the patients. Corresponding percentages for non-US countries were 74%, 61%, and 78% respectively. Developing or transition countries participated in 27% of the studies, providing 15% of the centers and 52% of the patients. The United States remains an important location for pediatric trials. Developing country involvement in pediatric drug development is not increasing, although these countries participate significantly in vaccine trials.

Re-inventing drug development: A case study of the I-SPY 2 breast cancer clinical trials program.

PubMed

Das, Sonya; Lo, Andrew W

2017-11-01

In this case study, we profile the I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And molecular anaLysis 2), a unique breast cancer clinical trial led by researchers at 20 leading cancer centers across the US, and examine its potential to serve as a model of drug development for other disease areas. This multicenter collaboration launched in 2010 to reengineer the drug development process to be more efficient and patient-centered. We conduct several interviews with the I-SPY leadership as well as a literature review of relevant publications to assess the I-SPY 2 initiative. To date, six drugs have graduated from I-SPY 2, identified as excellent candidates for phase 3 trials in their corresponding tumor subtype, and several others have been or are still being evaluated. These trials are also more efficient, typically involving fewer subjects and reaching conclusions more quickly, and candidates have more than twice the predicted likelihood of success in a smaller phase 3 setting compared to traditional trials. We observe that I-SPY 2 possesses several novel features that could be used as a template for more efficient and cost effective drug development, namely its adaptive trial design; precompetitive network of stakeholders; and flexible infrastructure to accommodate innovation. Copyright © 2017 Elsevier Inc. All rights reserved.

Testing moderation in network meta-analysis with individual participant data

PubMed Central

Dagne, Getachew A.; Brown, C. Hendricks; Howe, George; Kellam, Sheppard G.; Liu, Lei

2016-01-01

Summary Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data (IPD) may increase the sensitivity of NMA for detecting moderator effects, as compared to aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new network meta-analysis diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within- and between-trial heterogeneity, and can include participant-level covariates. Within this framework we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to IPD as compared to study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. PMID:26841367

Oral contraceptives containing drospirenone for premenstrual syndrome.

PubMed

Lopez, Laureen M; Kaptein, Adrian A; Helmerhorst, Frans M

2012-02-15

Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception. To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another combined oral contraceptive for effect on premenstrual symptoms. We searched for studies of drospirenone and premenstrual syndrome in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, and POPLINE (20 Dec 2011); EMBASE, LILACS, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (02 Mar 2011). We also examined references lists of relevant articles and wrote to known investigators to find other trials. We included randomized controlled trials in any language that compared a combined oral contraceptive (COC) containing drospirenone with a placebo or with another COC for effect on premenstrual symptoms. The primary outcome included affective and physical premenstrual symptoms that were prospectively recorded. Adverse events related to combined oral contraceptive use were examined. Two review authors independently extracted data and assessed study quality. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI). For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated. We included five trials with a total of 1920 women. Two placebo-controlled trials of women with PMDD showed less severe premenstrual symptoms after three months with drospirenone 3 mg plus ethinyl estradiol 20 μg than with placebo (MD -7.92; 95% CI -11.16 to -4.67). The drospirenone group had greater mean decreases in impairment of productivity (MD -0.31; 95% CI -0.55 to -0.08), social activities (MD -0.29; 95% CI -0.54 to -0.04), and relationships (MD -0.30; 95% CI -0.54 to -0.06). Side effects more common with the use of the drospirenone COC contraceptive were nausea, intermenstrual bleeding, and breast pain. The respective odds ratios were 3.15 (95% CI 1.90 to 5.22), 4.92 (95% CI 3.03 to 7.96), and 2.67 (95% CI 1.50 to 4.78). Total adverse events related to the study drug were more likely for the drospirenone COC group (OR 2.36; 95% CI 1.62 to 3.44). Three trials studied the effect of drospirenone 3 mg plus ethinyl estradiol 30 μg on less severe symptoms. A placebo-controlled six-month trial had insufficient data for primary outcome analysis. Another six-month study used levonorgestrel 150 µg plus ethinyl estradiol 30 µg for the comparison group but did not provide enough data on premenstrual symptoms. In a two-year trial, the drospirenone COC group had similar premenstrual symptoms to the comparison group given desogestrel 150 µg plus ethinyl estradiol 30 µg (OR 0.87; 95% CI 0.63 to 1.22). The groups were also similar for adverse events related to treatment (OR 1.02; 95% CI 0.78 to 1.33). Drospirenone 3 mg plus ethinyl estradiol 20 μg may help treat premenstrual symptoms in women with severe symptoms, that is, premenstrual dysphoric disorder. The placebo also had a large effect. We do not know whether the combined oral contraceptive works after three cycles, helps women with less severe symptoms, or is better than other oral contraceptives. Larger and longer trials of higher quality are needed to address these issues. Trials should follow CONSORT guidelines.

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

PubMed

Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

2015-09-01

Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Patient and family member perspectives on searching for cancer clinical trials: A qualitative interview study.

PubMed

Ridgeway, Jennifer L; Asiedu, Gladys B; Carroll, Katherine; Tenney, Meaghan; Jatoi, Aminah; Radecki Breitkopf, Carmen

2017-02-01

Clinical trials are vital in the context of ovarian cancer and may offer further treatment options during disease recurrence, yet enrollment remains low. Understanding patient and family member experiences with identifying trials can inform engagement and education efforts. Interviews were conducted with 33 patients who had experience with clinical trial conversations and 39 nominated family members. Thematic analysis examined experiences and generated findings for clinical practice. Trial conversations with providers at diagnosis were uncommon and often overwhelming. Most participants delayed engagement until later in the disease course. With hindsight, though, some wished they considered trials earlier. Difficulty identifying appropriate trials led some to defer searching to providers, but then they worried about missed opportunities. Most family members felt unqualified to search. Trial conversations during clinical encounters should start early and include specifying search responsibilities of providers, patients, and family. Patients and family members can be engaged in searches but need guidance. Trials should be discussed throughout the disease course, even if patients are not ready to participate or are not making a treatment decision. Education should focus on identifying trials that meet search criteria. Transparency regarding each individual's role in identifying trials is critical. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review and meta-analysis (protocol).

PubMed

Effiong, Andem; Kumari, Prerna

2018-02-14

This is the protocol for a systematic review (and meta-analysis) of an intervention. The primary objective of this systematic review will be to assess the benefits and harms of pharmacological therapies (pharmacotherapies) for the management of fatigue in adults with CLD of any etiology. The effects of pharmacological therapies on fatigue in CLD will be compared against those of placebo, no intervention, or non-pharmacological interventions. Specifically, this review will examine whether pharmacological therapies improve CLD-associated fatigue, and if they do, what key elements are associated with their effectiveness. The results of this systematic review will assist clinicians, policy-makers, researchers, and people with CLD in decision-making on how best to manage fatigue and its associated symptoms. MEDLINE, SCOPUS, EMBASE, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles and conference proceedings will be searched for relevant studies. No language or date restrictions will be applied. Eligible studies will include adults with CLD of any etiology. Included studies will be randomized controlled trials. From included studies, data on participant characteristics, study design, setting, research ethics compliance, and intervention outcomes will be extracted. Risk of bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A random-effects meta-analysis will be conducted. If substantial or considerable levels of heterogeneity are detected, analysis will be limited to a narrative synthesis. This systematic review will examine the effectiveness of pharmacological therapies on fatigue reduction in people with CLD. Such therapies may be more effective than non-pharmacological interventions in treating fatigue symptoms in CLD. Evidence derived from the findings of this study will guide future practice, policy, and research. PROSPERO, CRD42017076957.

Young People and Physical Activity: A Systematic Review Matching Their Views to Effective Interventions

ERIC Educational Resources Information Center

Rees, Rebecca; Kavanagh, J.; Harden, A.; Shepherd, J.; Brunton, G.; Oliver, S.; Oakley, A.

2006-01-01

A systematic review was conducted to examine the barriers to, and facilitators of, physical activity among young people (11-16 years). The review focused on the wider determinants of health, examining community- and society-level interventions. Four trials and 16 studies of young people's views were included. Evidence for the effectiveness of the…

Long-Term Effects of a Home-Visiting Intervention for Depressed Mothers and Their Infants

ERIC Educational Resources Information Center

Kersten-Alvarez, Laura E.; Hosman, Clemens M. H.; Riksen-Walraven, J. Marianne; Van Doesum, Karin T. M.; Hoefnagels, Cees

2010-01-01

Background: Whereas preventive interventions for depressed mothers and their infants have yielded positive short-term outcomes, few studies have examined their long-term effectiveness. The present follow-up of a randomised controlled trial (RCT) is one of the first to examine the longer-term effects of an intervention for mothers with postpartum…

Trial Courts in the Judicial Process.

ERIC Educational Resources Information Center

McKnight, R. Neal

1981-01-01

Describes a college course which examines the organizational and behavioral characteristics of trial courts in the American judicial process. A major course objective is to help students understand the trial court process as a political process by showing how trial court organizations are involved in the allocation of social values. (RM)

Physiological and Behavioral Parameters of Infants' Categorization: Changes in Heart Rate and Duration of Examining across Trials

ERIC Educational Resources Information Center

Elsner, Birgit; Pauen, Sabina; Jeschonek, Susanna

2006-01-01

This report investigates the relations between duration of examining and heart rate (HR) across several trials of an object-examination task. A total of N= 20 11-month-olds were familiarized with a sequence of 10 different exemplars from the same global category (animals or furniture) before they received an exemplar from the contrasting category…

The experience of adolescents participating in a randomised clinical trial in the field of mental health: a qualitative study.

PubMed

Midgley, Nick; Isaacs, Danny; Weitkamp, Katharina; Target, Mary

2016-07-28

This descriptive study aimed to investigate adolescents' motivations for participating in a randomised controlled trial (RCT), to explore the understanding that the young people had regarding a number of aspects of the trial design, to examine whether or not they found participation in the trial to be acceptable and what affected this, and to identify whether and how the young people felt that their participation in the RCT impacted on their experience of therapy and on therapeutic change. Seventy-six adolescents who were taking part in a large-scale RCT to evaluate the clinical and cost effectiveness of psychological therapies for depression were interviewed at two time-points after completing therapy. The semi-structured interviews, which included a focus on the young people's experience of the research study, were analysed using framework analysis. The vast majority of adolescents found it acceptable to participate in the clinical trial, and many agreed to participate for reasons of 'conditional altruism'. However consent was often given without great understanding of the key elements of the trial, including the difference between treatment arms and the randomisation process. Although the adolescents were largely positive about their experiences from taking part, the study raises questions about whether clinical outcomes may be influenced by participation in the research elements of the trial. Although adolescents are under-represented in clinical trials, those who do participate are generally positive about the experience; however, careful thought needs to be given to key elements of the trial design and the potential impact of the research participation on clinical outcomes. ISRCTN registry, ISRCTN83033550 . Registered on 15 October 2009.

Study design and rationale of the 'Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial': study protocol for a randomized controlled trial.

PubMed

Choi, Woong Gil; Rha, Seung Woon; Choi, Cheol Ung; Kim, Eung Ju; Oh, Dong Joo; Cho, Yoon Hyung; Park, Sang Ho; Lee, Seung Jin; Hur, Ae Yong; Ko, Young Guk; Park, Sang Min; Kim, Ki Chang; Kim, Joo Han; Kim, Min Woong; Kim, Sang Min; Bae, Jang Ho; Bong, Jung Min; Kang, Won Yu; Seo, Jae Bin; Jung, Woo Yong; Cho, Jang Hyun; Kim, Do Hoi; Ahn, Ji Hoon; Kim, Soo Hyun; Jang, Ji Yong

2016-06-25

The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.

Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

PubMed

Karaarslan, Numan; Yilmaz, Ibrahim; Ozbek, Hanefi; Caliskan, Tezcan; Topuk, Savas; Sirin, Duygu Yasar; Ates, Ozkan

2018-04-06

The aim of this study was to systematically investigate the role of artificial small interfering RNA (siRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and "glioblastoma," either individually or combined (\\"OR\\" and \\"AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. To be able to evaluate the clinical use of siRNAs, there is an urgent need for in-vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

Physical analysis of breast cancer using dual-source computed tomography

NASA Astrophysics Data System (ADS)

Kim, H. J.; Lee, H. K.; Cho, J. H.

2014-12-01

This study was aimed to analyze various physical characteristics of breast cancer using dual-source computed tomography (CT). A phantom study and a clinical trial were performed in order and a 64-multidetector CT device was used for the examinations. In the phantom study, single-source (SS) CT was set up with a conventional scanning condition that is usually applied for breast CT examination and implementation was done at tube voltage of 120 kVp. Dual-source CT acquired images by irradiating X-ray sources with fast switching between two kilovoltage settings (80 and 140 kVp). After scanning, Hounsfield Unit (HU) values and radiation doses in a region of interest were measured and analyzed. In the clinical trial, the HU values were measured and analyzed after single-source computed tomography (SSCT) and dual-source CT in patients diagnosed with breast cancer. Also, the tumor size measured by dual-source CT was compared with the actual tumor size. The phantom study determined that the tumor region was especially measured by dual-source CT, while nylon fiber and specks region were especially measured by SSCT. The radiation dose was high with dual-source CT. The clinical trial showed a higher HU value of cancerous regions when scanned by dual-source CT compared with SSCT.

Changes in the Precision of a Study from Planning Phase to Implementation Phase: Evidence from the First Wave of Group Randomized Trials Launched by the Institute of Education Sciences

ERIC Educational Resources Information Center

Spybrook, Jessaca; Lininger, Monica; Cullen, Anne

2011-01-01

The purpose of this study is to extend the work of Spybrook and Raudenbush (2009) and examine how the research designs and sample sizes changed from the planning phase to the implementation phase in the first wave of studies funded by IES. The authors examine the impact of the changes in terms of the changes in the precision of the study from the…

A Qualitative Study of Motivations for Minority Recruitment in Cancer Clinical Trials Across Five NCI-Designated Cancer Centers.

PubMed

Simoni, Zachary R; Martin, Michelle; Wenzel, Jennifer A; Cook, Elise D; Konety, Badrinath; Vickers, Selwyn M; Chen, Moon S; Foaud, Mona N; Durant, Raegan W

2016-11-08

Minority enrollment in cancer clinical trials is traditionally low. In light of this fact, numerous studies have investigated barriers to recruitment and retention within minority populations. However, very little research has investigated the importance of clinicians' and researchers' motivations for minority recruitment in cancer clinical trials. Therefore, we sought to examine motivations for minority recruitment across four professional stakeholder groups (principal investigators, clinicians, research staff, and Cancer Center leaders) at five National Cancer Institute (NCI)-designated Comprehensive Cancer Centers. This study is based on the data from 91 qualitative interviews conducted across the five NCI-designated Comprehensive Cancer Centers to investigate stakeholders' motivations for minority recruitment in cancer clinical trials. Emergent themes include (a) minority recruitment increases generalizability of cancer clinical trials, (b) minority recruitment is motivated by social justice, (c) some institutions promote minority recruitment through the use of supplemental financial support, (d) federal funding requirements for minority inclusion in clinical research motivate investigators to focus on minority recruitment, and (e) some stakeholders favor a more race-neutral approach to participant recruitment rather than an emphasis on targeted minority recruitment. The perspectives of clinical and research stakeholders potentially inform the assessment of existing strategies and the development of new strategies to increase motivation for minority recruitment in cancer clinical trials.

Strategies to improve the implementation of healthy eating, physical activity and obesity prevention policies, practices or programmes within childcare services.

PubMed

Wolfenden, Luke; Jones, Jannah; Williams, Christopher M; Finch, Meghan; Wyse, Rebecca J; Kingsland, Melanie; Tzelepis, Flora; Wiggers, John; Williams, Amanda J; Seward, Kirsty; Small, Tameka; Welch, Vivian; Booth, Debbie; Yoong, Sze Lin

2016-10-04

Despite the existence of effective interventions and best-practice guideline recommendations for childcare services to implement policies, practices and programmes to promote child healthy eating, physical activity and prevent unhealthy weight gain, many services fail to do so. The primary aim of the review was to examine the effectiveness of strategies aimed at improving the implementation of policies, practices or programmes by childcare services that promote child healthy eating, physical activity and/or obesity prevention. The secondary aims of the review were to:1. describe the impact of such strategies on childcare service staff knowledge, skills or attitudes;2. describe the cost or cost-effectiveness of such strategies;3. describe any adverse effects of such strategies on childcare services, service staff or children;4. examine the effect of such strategies on child diet, physical activity or weight status. We searched the following electronic databases on 3 August 2015: the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, ERIC, CINAHL and SCOPUS. We also searched reference lists of included trials, handsearched two international implementation science journals and searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp/) and ClinicalTrials.gov (www.clinicaltrials.gov). We included any study (randomised or non-randomised) with a parallel control group that compared any strategy to improve the implementation of a healthy eating, physical activity or obesity prevention policy, practice or programme by staff of centre-based childcare services to no intervention, 'usual' practice or an alternative strategy. The review authors independently screened abstracts and titles, extracted trial data and assessed risk of bias in pairs; we resolved discrepancies via consensus. Heterogeneity across studies precluded pooling of data and undertaking quantitative assessment via meta-analysis. However, we narratively synthesised the trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We identified 10 trials as eligible and included them in the review. The trials sought to improve the implementation of policies and practices targeting healthy eating (two trials), physical activity (two trials) or both healthy eating and physical activity (six trials). Collectively the implementation strategies tested in the 10 trials included educational materials, educational meetings, audit and feedback, opinion leaders, small incentives or grants, educational outreach visits or academic detailing. A total of 1053 childcare services participated across all trials. Of the 10 trials, eight examined implementation strategies versus a usual practice control and two compared alternative implementation strategies. There was considerable study heterogeneity. We judged all studies as having high risk of bias for at least one domain.It is uncertain whether the strategies tested improved the implementation of policies, practices or programmes that promote child healthy eating, physical activity and/or obesity prevention. No intervention improved the implementation of all policies and practices targeted by the implementation strategies relative to a comparison group. Of the eight trials that compared an implementation strategy to usual practice or a no intervention control, however, seven reported improvements in the implementation of at least one of the targeted policies or practices relative to control. For these trials the effect on the primary implementation outcome was as follows: among the three trials that reported score-based measures of implementation the scores ranged from 1 to 5.1; across four trials reporting the proportion of staff or services implementing a specific policy or practice this ranged from 0% to 9.5%; and in three trials reporting the time (per day or week) staff or services spent implementing a policy or practice this ranged from 4.3 minutes to 7.7 minutes. The review findings also indicate that is it uncertain whether such interventions improve childcare service staff knowledge or attitudes (two trials), child physical activity (two trials), child weight status (two trials) or child diet (one trial). None of the included trials reported on the cost or cost-effectiveness of the intervention. One trial assessed the adverse effects of a physical activity intervention and found no difference in rates of child injury between groups. For all review outcomes, we rated the quality of the evidence as very low. The primary limitation of the review was the lack of conventional terminology in implementation science, which may have resulted in potentially relevant studies failing to be identified based on the search terms used in this review. Current research provides weak and inconsistent evidence of the effectiveness of such strategies in improving the implementation of policies and practices, childcare service staff knowledge or attitudes, or child diet, physical activity or weight status. Further research in the field is required.

Postoperative Adverse Events Inconsistently Improved by the World Health Organization Surgical Safety Checklist: A Systematic Literature Review of 25 Studies.

PubMed

de Jager, Elzerie; McKenna, Chloe; Bartlett, Lynne; Gunnarsson, Ronny; Ho, Yik-Hong

2016-08-01

The World Health Organization Surgical Safety Checklist (SSC) has been widely implemented in an effort to decrease surgical adverse events. This systematic literature review examined the effects of the SSC on postoperative outcomes. The review included 25 studies: two randomised controlled trials, 13 prospective and ten retrospective cohort trials. A meta-analysis was not conducted as combining observational studies of heterogeneous quality may be highly biased. The quality of the studies was largely suboptimal; only four studies had a concurrent control group, many studies were underpowered to examine specific postoperative outcomes and teamwork-training initiatives were often combined with the implementation of the checklist, confounding the results. The effects of the checklist were largely inconsistent. Postoperative complications were examined in 20 studies; complication rates significantly decreased in ten and increased in one. Eighteen studies examined postoperative mortality. Rates significantly decreased in four and increased in one. Postoperative mortality rates were not significantly decreased in any studies in developed nations, whereas they were significantly decreased in 75 % of studies conducted in developing nations. The checklist may be associated with a decrease in surgical adverse events and this effect seems to be greater in developing nations. With the observed incongruence between specific postoperative outcomes and the overall poor study designs, it is possible that many of the positive changes associated with the use of the checklist were due to temporal changes, confounding factors and publication bias.

Effects of a Carbohydrate-Electrolyte Drink on Specific Soccer Tests and Performance

PubMed Central

Ostojic, Sergej M.; Mazic, Sanja

2002-01-01

The aim of this study was to examine the effects of a carbohydrate-electrolyte drink on specific soccer tests and performance. Twenty-two professional male soccer players volunteered to participate in the study. The players were allocated to two assigned trials ingesting carbohydrate-electrolyte drink (7% carbohydrates, sodium 24 mmol.l-1, chloride 12 mmol.l-1, potassium 3 mmol.l-1) or placebo during a 90 min on-field soccer match. The trials were matched for subjects’ age, weight, height and maximal oxygen uptake. Immediately after the match, players completed four soccer-specific skill tests. Blood glucose concentration [mean (SD)] was higher at the end of the match-play in the carbohydrate-electrolyte trial than in the placebo trial (4.4 (0.3) vs. 4.0 (0.3) mmol.l-1, P < 0.05). Subjects in the carbohydrate-electrolyte trial finished the specific dribble test faster in comparison with subjects in the placebo trial (12.9 (0.4) vs. 13.6 (0.5) s, P < 0.05). Ratings of the precision test were higher in the carbohydrate-electrolyte trial as compared to the placebo trial (17.2 (4.8) vs. 15.1 (5.2), P < 0.05) but there were no differences in coordination test and power test results between trials. The main finding of the present study indicates that supplementation with carbohydrate-electrolyte solution improved soccer-specific skill performance and recovery after an on-field soccer match compared with ingestion of placebo. This suggests that soccer players should consume carbohydrate-electrolyte fluid throughout a game to help prevent deterioration in specific skill performance. PMID:24688270

African American women's perceptions of cancer clinical trials

PubMed Central

Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

2014-01-01

Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

When Justice Is Up to You. Celebrating America's Guarantee of Trial by Jury.

ERIC Educational Resources Information Center

National Inst. for Citizen Education in the Law, Washington, DC.

Featuring a mock trial tested in the District of Columbia, the objective of this manual is to help students learn more about the constitutional guarantee of trial by jury. Prepared as five separate lessons, the manual examines one alternative to the jury system--trial by ordeal; traces the development of the guarantee of trial by jury; explores…

Sensitivity study of Space Station Freedom operations cost and selected user resources

NASA Technical Reports Server (NTRS)

Accola, Anne; Fincannon, H. J.; Williams, Gregory J.; Meier, R. Timothy

1990-01-01

The results of sensitivity studies performed to estimate probable ranges for four key Space Station parameters using the Space Station Freedom's Model for Estimating Space Station Operations Cost (MESSOC) are discussed. The variables examined are grouped into five main categories: logistics, crew, design, space transportation system, and training. The modification of these variables implies programmatic decisions in areas such as orbital replacement unit (ORU) design, investment in repair capabilities, and crew operations policies. The model utilizes a wide range of algorithms and an extensive trial logistics data base to represent Space Station operations. The trial logistics data base consists largely of a collection of the ORUs that comprise the mature station, and their characteristics based on current engineering understanding of the Space Station. A nondimensional approach is used to examine the relative importance of variables on parameters.

The Placebo Effect in Clinical Trials for Alcohol Dependence: An Exploratory Analysis of 51 Naltrexone and Acamprosate Studies

PubMed Central

Litten, Raye Z.; Castle, I-Jen P.; Falk, Daniel; Ryan, Megan; Fertig, Joanne; Chen, Chiung M.; Yi, Hsiao-ye

2013-01-01

Background The placebo effect often undermines efforts to determine treatment effectiveness in clinical trials. A significant placebo response occurs in alcohol trials, but it is not well understood. The purpose of this study was to characterize the placebo response across multiple naltrexone and acamprosate studies. Methods Fifty-one trials, 3 with a naltrexone and an acamprosate arm, 31 with at least 1 naltrexone arm, and 17 with at least 1 acamprosate arm, were identified from Cochrane reviews and PubMed search. To be included in this study, patients had to be at least 18 years old, abstinent from alcohol before randomization, and meet a diagnosis of alcohol dependence. Pearson correlation coefficients (rp) and simple linear regression were used to describe the strength of linear relationships between placebo response and treatment effect size. Spearman’s rank correlation coefficients (rs) were used to examine the strength of associations between study characteristics and placebo response. Results For the end-point measures of percent days abstinent and total abstinence, a negative relationship was evident between placebo response and treatment effect size in the naltrexone trials (rp = −0.55, p < 0.01 and rp = −0.20, p = 0.35, respectively) as well as in the acamprosate trials (rp = −0.45, p = 0.09 and rp = −0.56, p = 0.01, respectively). The placebo response for percent days abstinent was negatively correlated with mean age of participants (rs = −0.42, p = 0.05) across naltrexone trials and positively correlated with publication year (rs = 0.57, p = 0.03) across acamprosate trials. However, these two study characteristics were not significantly correlated with treatment effect size. Conclusion The placebo response varied considerably across trials and was negatively correlated with the treatment effect size. Additional studies are required to fully understand the complex nature of the placebo response and to evaluate approaches to minimize its effects. PMID:23889231

Sensitivity and specificity of a digit symbol recognition trial in the identification of response bias.

PubMed

Kim, Nancy; Boone, Kyle B; Victor, Tara; Lu, Po; Keatinge, Carolyn; Mitchell, Cary

2010-08-01

Recently published practice standards recommend that multiple effort indicators be interspersed throughout neuropsychological evaluations to assess for response bias, which is most efficiently accomplished through use of effort indicators from standard cognitive tests already included in test batteries. The present study examined the utility of a timed recognition trial added to standard administration of the WAIS-III Digit Symbol subtest in a large sample of "real world" noncredible patients (n=82) as compared with credible neuropsychology clinic patients (n=89). Scores from the recognition trial were more sensitive in identifying poor effort than were standard Digit Symbol scores, and use of an equation incorporating Digit Symbol Age-Corrected Scaled Scores plus accuracy and time scores from the recognition trial was associated with nearly 80% sensitivity at 88.7% specificity. Thus, inclusion of a brief recognition trial to Digit Symbol administration has the potential to provide accurate assessment of response bias.

Assessing noninferiority in a three-arm trial using the Bayesian approach.

PubMed

Ghosh, Pulak; Nathoo, Farouk; Gönen, Mithat; Tiwari, Ram C

2011-07-10

Non-inferiority trials, which aim to demonstrate that a test product is not worse than a competitor by more than a pre-specified small amount, are of great importance to the pharmaceutical community. As a result, methodology for designing and analyzing such trials is required, and developing new methods for such analysis is an important area of statistical research. The three-arm trial consists of a placebo, a reference and an experimental treatment, and simultaneously tests the superiority of the reference over the placebo along with comparing this reference to an experimental treatment. In this paper, we consider the analysis of non-inferiority trials using Bayesian methods which incorporate both parametric as well as semi-parametric models. The resulting testing approach is both flexible and robust. The benefit of the proposed Bayesian methods is assessed via simulation, based on a study examining home-based blood pressure interventions. Copyright © 2011 John Wiley & Sons, Ltd.

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

PubMed Central

Wiljer, David; Cafazzo, Joseph A

2016-01-01

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r2=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients. PMID:27613084

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods.

PubMed

Pham, Quynh; Wiljer, David; Cafazzo, Joseph A

2016-09-09

Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η(2)=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η(2)=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η(2)=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.

Psychosocial interventions for internalised stigma in people with a schizophrenia-spectrum diagnosis: A systematic narrative synthesis and meta-analysis.

PubMed

Wood, Lisa; Byrne, Rory; Varese, Filippo; Morrison, Anthony P

2016-10-01

It is acknowledged that people with a schizophrenia-spectrum diagnosis experience higher levels of stigma compared to any other mental health diagnosis. As a consequence, their experience of internalised stigma is likely to be the most detrimental and pervasive. Internalised stigma interventions have shown some benefits in those who experience serious mental illness including those with a schizophrenia-spectrum diagnosis. A systematic narrative review and meta-analysis were conducted examining the efficacy of internalised stigma interventions for people with a schizophrenia-spectrum diagnosis. Randomised Controlled Trials, controlled trials, and cohort studies were included and assessed against quality criteria. The search identified 12 studies; 7 randomised controlled trials, 3 cohort studies and 2 controlled trials. A variety of psychosocial interventions were utilised with the majority employing Cognitive Behaviour Therapy (CBT), psychoeducation and social skills training. The core outcomes used to examine the efficacy of the intervention were internalised stigma, self-esteem, empowerment, and functioning. The meta-analysis revealed an improvement in internalised stigma favouring the internalised stigma intervention but was not significant (5 RCTs, n=200). Self-efficacy and insight were significantly improved favouring the internalised stigma intervention. Internalised stigma interventions show promise in those with schizophrenia-spectrum diagnoses. Existing interventions have demonstrated small effects and employed small samples. Large scale RCTs are required to further develop the evidence base of more targeted interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Meta-analysis of trials of streptococcal throat treatment programs to prevent rheumatic fever.

PubMed

Lennon, Diana; Kerdemelidis, Melissa; Arroll, Bruce

2009-07-01

Rheumatic fever (RF) is the commonest cause of pediatric heart disease globally. Penicillin for streptococcal pharyngitis prevents RF. Inequitable access to health care persists. To investigate RF prevention by treating streptococcal pharyngitis in school- and/or community-based programs. Medline, Old Medline, the Cochrane Library, DARE, Central, NHS, EED, NICE, NRMC, Clinical Evidence, CDC website, PubMed, and reference lists of retrieved articles. Known researchers in the field were contacted where possible. Randomized, controlled trials or trials of before/after design examining treatment of sore throats in schools or communities with RF as an outcome where data were able to be pooled for analysis. Two authors examined titles, abstracts, selected articles, and extracted data. Disagreements were resolved by consensus. QUANTITATIVE ANALYSIS TOOL: Review Manager version 4.2 to assess pooled relative risks and 95% confidence intervals. Six studies (of 677 screened) which met the criteria and could be pooled were included. Meta-analysis of these trials for RF control produced a relative risk of 0.41 (95% CI: 0.23-0.70). There was statistical heterogeneity (I = 70.5%). Hence a random effects analysis was conducted. Many studies were poor quality. Title and available abstracts of non-English studies were checked. There may be publication bias. This is the best available evidence in an area with imperfect information. It is expected acute RF cases would diminish by about 60% using a school or community clinic to treat streptococcal pharyngitis. This should be considered in high-risk populations.

DESIGN OF THE SILENT CEREBRAL INFARCT TRANSFUSION (SIT) TRIAL

PubMed Central

Casella, James F.; King, Allison A.; Barton, Bruce; White, Desiree A.; Noetzel, Michael J.; Ichord, Rebecca N.; Terrill, Cindy; Hirtz, Deborah; McKinstry, Robert C.; Strouse, John J.; Howard, Thomas H.; Coates, Thomas D.; Minniti, Caterina P; Campbell, Andrew D.; Vendt, Bruce A.; Lehmann, Harold; DeBaun, Michael R.

2017-01-01

Background Silent cerebral infarct (SCI) is the most common cause of serious neurological disease in sickle cell anemia (SCA), affecting approximately 22% of children. The goal of this trial is to determine whether blood transfusion therapy will reduce further neurological morbidity in children with SCI, and if so, the magnitude of this benefit. Procedure The Silent Cerebral Infarct Transfusion (SIT) Trial includes 29 clinical sites and 3 subsites, a Clinical Coordinating Center, and a Statistical and Data Coordinating Center, to test the following hypothesis: prophylactic blood transfusion therapy in children with SCI will result in at least an 86% reduction in the rate of subsequent overt strokes or new or progressive cerebral infarcts as defined by magnetic resonance imaging (MRI) of the brain. The intervention is blood transfusion versus observation. Two hundred and four participants (102 in each treatment assignment) will ensure 85% power to detect the effect necessary to recommend transfusion therapy (86% reduction), after accounting for 10% drop out and 19% crossover rates. MRI examination of the brain is done at screening, immediately before randomization and study exit. Each randomly assigned participant receives a cognitive test battery at study entry, 12–18 months later, and study exit and an annual neurological examination. Blood is obtained from all screened participants for a biologic repository containing serum and a renewable source of DNA. Conclusion The SIT Trial could lead to a change in standard care practices for children affected with SCA and SCI, with a consequent reduction in neurological morbidity. PMID:20201689

One-stage individual participant data meta-analysis models: estimation of treatment-covariate interactions must avoid ecological bias by separating out within-trial and across-trial information.

PubMed

Hua, Hairui; Burke, Danielle L; Crowther, Michael J; Ensor, Joie; Tudur Smith, Catrin; Riley, Richard D

2017-02-28

Stratified medicine utilizes individual-level covariates that are associated with a differential treatment effect, also known as treatment-covariate interactions. When multiple trials are available, meta-analysis is used to help detect true treatment-covariate interactions by combining their data. Meta-regression of trial-level information is prone to low power and ecological bias, and therefore, individual participant data (IPD) meta-analyses are preferable to examine interactions utilizing individual-level information. However, one-stage IPD models are often wrongly specified, such that interactions are based on amalgamating within- and across-trial information. We compare, through simulations and an applied example, fixed-effect and random-effects models for a one-stage IPD meta-analysis of time-to-event data where the goal is to estimate a treatment-covariate interaction. We show that it is crucial to centre patient-level covariates by their mean value in each trial, in order to separate out within-trial and across-trial information. Otherwise, bias and coverage of interaction estimates may be adversely affected, leading to potentially erroneous conclusions driven by ecological bias. We revisit an IPD meta-analysis of five epilepsy trials and examine age as a treatment effect modifier. The interaction is -0.011 (95% CI: -0.019 to -0.003; p = 0.004), and thus highly significant, when amalgamating within-trial and across-trial information. However, when separating within-trial from across-trial information, the interaction is -0.007 (95% CI: -0.019 to 0.005; p = 0.22), and thus its magnitude and statistical significance are greatly reduced. We recommend that meta-analysts should only use within-trial information to examine individual predictors of treatment effect and that one-stage IPD models should separate within-trial from across-trial information to avoid ecological bias. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Music interventions for mechanically ventilated patients.

PubMed

Bradt, Joke; Dileo, Cheryl; Grocke, Denise

2010-12-08

Mechanical ventilation often causes major distress and anxiety in patients. Music interventions have been used to reduce anxiety and distress and improve physiological functioning in medical patients; however its efficacy for mechanically ventilated patients needs to be evaluated. To examine the effects of music interventions with standard care versus standard care alone on anxiety and physiological responses in mechanically ventilated patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1), MEDLINE, CINAHL, AMED, EMBASE, PsycINFO, LILACS, Science Citation Index, www.musictherapyworld.net, CAIRSS for Music, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the National Research Register, and NIH CRISP (all to January 2010). We handsearched music therapy journals and reference lists and contacted relevant experts to identify unpublished manuscripts. There was no language restriction. We included all randomized and quasi-randomized controlled trials that compared music interventions and standard care with standard care alone for mechanically ventilated patients. Two authors independently extracted the data and assessed the methodological quality. Additional information was sought from the trial researchers, when necessary. Results were presented using mean differences for outcomes measured by the same scale and standardized mean differences for outcomes measured by different scales. Post-test scores were used. In cases of significant baseline difference, we used change scores. We included eight trials (213 participants). Music listening was the main intervention used, and seven of the studies did not include a trained music therapist. Results indicated that music listening may be beneficial for anxiety reduction in mechanically ventilated patients; however, these results need to be interpreted with caution due to the small sample size. Findings indicated that listening to music consistently reduced heart rate and respiratory rate, suggesting a relaxation response. No strong evidence was found for blood pressure reduction.Music listening did not improve oxygen saturation level.No studies could be found that examined the effects of music interventions on quality of life, patient satisfaction, post-discharge outcomes, mortality, or cost-effectiveness. Music listening may have a beneficial effect on heart rate, respiratory rate, and anxiety in mechanically ventilated patients. However, the quality of the evidence is not strong. Most studies examined the effects of listening to pre-recorded music. More research is needed on the effects of music offered by a trained music therapist.

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.

Issues in recruiting community-dwelling stroke survivors to clinical trials: the AMBULATE trial.

PubMed

Lloyd, Gemma; Dean, Catherine M; Ada, Louise

2010-07-01

Recruitment to clinical trials is often slow and difficult, with a growing body of research examining this issue. However there is very little work related to stroke. The aim of this study was to examine the success and efficiency of recruitment of community-dwelling stroke survivors over the first two years of a clinical trial aiming to improve community ambulation. Recruitment strategies fell into 2 broad categories: (i) advertisement (such as newspaper advertising and media releases), and (ii) referral (via hospital and community physiotherapists, a stroke liaison officer and other researchers). Records were kept of the number of people who were screened, were eligible and were recruited for each strategy. The recruitment target of 60 in the first two years was not met. 111 stroke survivors were screened and 57 were recruited (i.e., a recruitment rate of 51%). The most successful strategy was referral via hospital-based physiotherapists (47% of recruited participants) and the least successful were media release and local newspaper advertising. The referral strategies were all more efficient than any of the advertisement strategies. In general, recruitment was inefficient and costly in terms of human resources. Given that stroke research is underfunded, it is important to find efficient ways of recruiting stroke survivors to clinical trials. An Australian national database similar to other disease-specific data bases (such as the National Cancer Database) is under development. In the interim, recruiting for several clinical trials at once may increase efficiency.

The Scopes trial and creation thought since 1925

NASA Astrophysics Data System (ADS)

Spaid, Mark Richard

The purpose of this study was to examine the role of the Scopes Trial of 1925 as the beginning of the battle between Creation Thought and Evolutionary Science in the public school classrooms. Historical analysis of events, legislation and a legal case study was used to synthesize the ideas and philosophies that guided events this century leading up the trial in Dayton, Tennessee during July of 1925. The study examined the development of the concept of a wall of separation between Church and State that began with Thomas Jefferson and James Madison and developed into the key component of the First Amendment to the U. S. Constitution. This concept was applied to the case analysis, legislation and school district policies regarding Creation and Evolution. The concepts of Creation and Evolution were examined and compared as a basis for understanding the conflict that exists between the Religious Right and the scientific community. The main personalities and their motives on both sides were highlighted because of the fact that the conflict still continues. The study sought solutions for practicing administrators who are faced with the controversy of Creation and Evolution in their schools. The question that guided the study was, "Is Accommodation possible or is Separation necessary?" The study examined legislation and court cases seeking the right answer for schools in their constant struggle with the two diametrically opposed philosophies. Analysis of the historical evidence and the events surrounding the issue since the inception of the United States concluded that there is no room for Accommodation with the First Amendment. Separation has been and should continue to be the guiding principle whenever the line between Church and State begins to blur. The collaboration between Church and State can prove harmful for both and the best way to insure their survival and proliferation is to keep them separate.

PubMed Central

Marchand, R.

1993-01-01

Three recent articles are examined in which research using the double-blind randomised clinical trial, the case control study, and the quasi-cohort study is described. Understanding the advantages and disadvantages of these methods makes it easier to grasp the pneumococcal vaccine controversy and make an informed choice. PMID:8499794

Examining the effectiveness of home-based parent aide services to reduce risk for physical child abuse and neglect: six-month findings from a randomized clinical trial.

PubMed

Guterman, Neil B; Tabone, Jiyoung K; Bryan, George M; Taylor, Catherine A; Napoleon-Hanger, Cynthia; Banman, Aaron

2013-08-01

This study set out to carry out a feasible, real-world, randomized clinical trial to examine the benefits of home-based paraprofessional parent aide services in reducing physical abuse and neglect risk in high-risk parents. Families were randomly assigned to receive either parent aide plus case management services (n = 73) or case management services only (n = 65), collecting in-home data on physical child abuse and neglect and proximal risk and protective factors, just prior to service initiation, and again after six months of services. Mothers receiving parent aide and case management services reported significant improvements from baseline to six-month follow-up in self-reported indicators of physical child abuse risk, as well as improvements on parental stress, mastery, depression, and anxiety, whereas mothers receiving only case management services did not. The slopes of such observed changes across groups, however, were not found to be statistically significantly different. No discernable improvements were found with regard to indicators of risk for child neglect. As the first randomized clinical trial examining the effectiveness of parent aide services, this study provides the first controlled evidence examining the potential benefits of this service modality. This study suggests promising trends regarding the benefit of parent aide services with respect to physical child abuse risk reduction and related predictors, but evidence does not appear to suggest that such services, as they are presently delivered, reduce child neglect. These findings support the continued use of parent aide services in cases of physical child abuse and also suggest careful consideration of the ways such services may be better configured to extend their impact, particularly with respect to child neglect risk. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relaxation techniques for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Crowther, Caroline A

2011-12-07

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of relaxation therapies for pain management in labour. To examine the effects of relaxation methods for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2010), The Cochrane Complementary Medicine Field's Trials Register (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 30 November 2010), CINAHL (1980 to 30 November 2010), the Australian and New Zealand Clinical Trial Registry (30 November 2010), Chinese Clinical Trial Register (30 November 2010), Current Controlled Trials (30 November 2010), ClinicalTrials.gov, (30 November 2010) ISRCTN Register (30 November 2010), National Centre for Complementary and Alternative Medicine (NCCAM) (30 November 2010) and the WHO International Clinical Trials Registry Platform (30 November 2010). Randomised controlled trials comparing relaxation methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Three review authors independently assessed trials for inclusion and extracted data. Data were checked for accuracy. Two review authors independently assessed trial quality. We attempted to contact study authors for additional information. We included 11 studies (1374 women) in the review. Relaxation was associated with a reduction in pain intensity during the latent phase (mean difference (MD) -1.25, 95% confidence interval (CI) -1.97 to -0.53, one trial, 40 women) and active phase of labour (MD -2.48, 95% CI -3.13 to 0.83, two trials, 74 women). There was evidence of improved outcomes from relaxation instruction with increased satisfaction with pain relief (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women) and lower assisted vaginal delivery (RR 0.07, 95% CI 0.01 to 0.50, two trials, 86 women). Yoga was associated with reduced pain (mean difference (MD) -6.12, 95% CI -11.77 to -0.47), one trial, 66 women), increased satisfaction with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women), satisfaction with the childbirth experience (MD) 6.34, 95% CI 0.26 to 12.42, one trial, 66 women), and reduced length of labour when compared to usual care (MD -139.91, 95% CI -252.50 to -27.32, one trial, 66 women) and when compared with supine position (MD -191.34, 95% CI -243.72 to -138.96, one trial, 83 women). Trials evaluating music and audio analgesia found no difference between groups in the primary outcomes pain intensity, satisfaction with pain relief, and caesarean delivery. The risk of bias was unclear for the majority of trials. Relaxation and yoga may have a role with reducing pain, increasing satisfaction with pain relief and reducing the rate of assisted vaginal delivery. There was insufficient evidence for the role of music and audio-analgesia. However, there is a need for further research.

Utilization of Clinical Trials Registries in Obstetrics and Gynecology Systematic Reviews.

PubMed

Bibens, Michael E; Chong, A Benjamin; Vassar, Matt

2016-02-01

To evaluate the use of clinical trials registries in published obstetrics and gynecologic systematic reviews and meta-analyses. We performed a metaepidemiologic study of systematic reviews between January 1, 2007, and December 31, 2015, from six obstetric and gynecologic journals (Obstetrics & Gynecology, Obstetrical & Gynecological Survey, Human Reproduction Update, Gynecologic Oncology, British Journal of Obstetrics and Gynaecology, and American Journal of Obstetrics & Gynecology). All systematic reviews included after exclusions were independently reviewed to determine whether clinical trials registries had been included as part of the search process. Studies that reported using a trials registry were further examined to determine whether trial data were included in the analysis of these systematic reviews. Our initial search resulted in 292 articles, which was narrowed to 256 after exclusions. Of the 256 systematic reviews meeting our selection criteria, 47 (18.4%) used a clinical trials registry. Eleven of the 47 (23.4%) systematic reviews found unpublished data and two included unpublished data in their results. A majority of systematic reviews in clinical obstetrics and gynecology journals do not conduct searches of clinical trials registries or do not make use of data obtained from these searches. Failure to make use of such data may lead to an inaccurate summary of available evidence and may contribute to an overrepresentation of published, statistically significant outcomes.

Challenges to recruitment and retention of African Americans in the gene-environment trial of response to dietary interventions (GET READI) for heart health

PubMed Central

Kennedy, Betty M.; Harsha, David W.; Bookman, Ebony B.; Hill, Yolanda R.; Rankinen, Tuomo; Rodarte, Ruben Q.; Murla, Connie D.

2011-01-01

In this paper, challenges to recruiting African Americans specifically for a dietary feeding trial are examined, learning experiences gained and suggestions to overcome these challenges in future trials are discussed. A total of 333 individuals were randomized in the trial and 234 (167 sibling pairs and 67 parents/siblings) completed the dietary intervention and required DNA blood sampling for genetic analysis. The trial used multiple strategies for recruitment. Hand distributed letters and flyers through mass distribution at various churches resulted in the largest number (n = 153, 46%) of African Americans in the trial. Word of mouth accounted for the second largest number (n = 120, 36%) and included prior study participants. These two recruitment sources represented 82% (n = 273) of the total number of individuals randomized in GET READI. The remaining 18% (n = 60) consisted of a combination of sources including printed message on check stubs, newspaper articles, radio and TV appearances, screening events and presentations. Though challenging, the recruitment efforts for GET READI produced a significant number of African American participants despite the inability to complete the trial as planned because of low recruitment yields. Nevertheless, the recruitment process produced substantial numbers that successfully completed all study requirements. PMID:21865154

Simultaneous sequential monitoring of efficacy and safety led to masking of effects.

PubMed

van Eekelen, Rik; de Hoop, Esther; van der Tweel, Ingeborg

2016-08-01

Usually, sequential designs for clinical trials are applied on the primary (=efficacy) outcome. In practice, other outcomes (e.g., safety) will also be monitored and influence the decision whether to stop a trial early. Implications of simultaneous monitoring on trial decision making are yet unclear. This study examines what happens to the type I error, power, and required sample sizes when one efficacy outcome and one correlated safety outcome are monitored simultaneously using sequential designs. We conducted a simulation study in the framework of a two-arm parallel clinical trial. Interim analyses on two outcomes were performed independently and simultaneously on the same data sets using four sequential monitoring designs, including O'Brien-Fleming and Triangular Test boundaries. Simulations differed in values for correlations and true effect sizes. When an effect was present in both outcomes, competition was introduced, which decreased power (e.g., from 80% to 60%). Futility boundaries for the efficacy outcome reduced overall type I errors as well as power for the safety outcome. Monitoring two correlated outcomes, given that both are essential for early trial termination, leads to masking of true effects. Careful consideration of scenarios must be taken into account when designing sequential trials. Simulation results can help guide trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

Re-examination of "release-from-PI" phenomena: recall accuracy does not recover after a semantic switch.

PubMed

Hubbard, Nicholas A; Weaver, Travis P; Turner, Monroe P; Rypma, Bart

2018-01-29

Recall accuracy decreases over successive memory trials using similar memoranda. This effect reflects proactive interference (PI) - the tendency for previously studied information to reduce recall of new information. However, recall improves if memoranda for a subsequent trial are semantically dissimilar from the previous trials. This improvement is thought to reflect a release from PI. We tested whether PI is reduced or released from the semantic category for which it had been induced by employing paradigms which featured inducement, semantic switch, and then return-to-original category epochs. Two experiments confirmed that PI was not released after various semantic switch trials (effects from d = -0.93 to -1.6). Combined analyses from both studies demonstrated that the number of intervening new category trials did not reduce or release PI. In fact, in all conditions recall accuracy decreased, demonstrating that PI is maintained and can increase after the new category trials. The release-from-PI account cannot accommodate these broader dynamics of PI. This account is also incongruent with evidence and theory from cognitive psychology, linguistics, and neuroscience. We propose a reintroduction-of-PI account which explains these broader PI dynamics and is consistent with the wider psychological and neurosciences.

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

PubMed

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

2012-08-28

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

POLICY IMPLICATIONS OF ADJUSTING RANDOMIZED TRIAL DATA FOR ECONOMIC EVALUATIONS: A DEMONSTRATION FROM THE ASCUS-LSIL TRIAGE STUDY

PubMed Central

Campos, Nicole G.; Castle, Philip E.; Schiffman, Mark; Kim, Jane J.

2013-01-01

Background Although the randomized controlled trial (RCT) is widely considered the most reliable method for evaluation of health care interventions, challenges to both internal and external validity exist. Thus, the efficacy of an intervention in a trial setting does not necessarily represent the real-world performance that decision makers seek to inform comparative effectiveness studies and economic evaluations. Methods Using data from the ASCUS-LSIL Triage Study (ALTS), we performed a simplified economic evaluation of age-based management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) among women who were referred to the study with low-grade squamous intraepithelial lesions (LSIL). We used data from the trial itself to adjust for 1) potential lead time bias and random error that led to variation in the observed prevalence of CIN3 by study arm, and 2) potential ascertainment bias among providers in the most aggressive management arm. Results We found that using unadjusted RCT data may result in counterintuitive cost-effectiveness results when random error and/or bias are present. Following adjustment, the rank order of management strategies changed for two of the three age groups we considered. Conclusion Decision analysts need to examine study design, available trial data and cost-effectiveness results closely in order to detect evidence of potential bias. Adjustment for random error and bias in RCTs may yield different policy conclusions relative to unadjusted trial data. PMID:22147881

The Effects of Industry Sponsorship on Comparator Selection in Trial Registrations for Neuropsychiatric Conditions in Children

PubMed Central

Dunn, Adam G.; Mandl, Kenneth D.; Coiera, Enrico; Bourgeois, Florence T.

2013-01-01

Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials. PMID:24376857

The effects of industry sponsorship on comparator selection in trial registrations for neuropsychiatric conditions in children.

PubMed

Dunn, Adam G; Mandl, Kenneth D; Coiera, Enrico; Bourgeois, Florence T

2013-01-01

Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials.

Equipoise, design bias, and randomized controlled trials: the elusive ethics of new drug development.

PubMed

Fries, James F; Krishnan, Eswar

2004-01-01

The concept of 'equipoise', or the 'uncertainty principle', has been represented as a central ethical principle, and holds that a subject may be enrolled in a randomized controlled trial (RCT) only if there is true uncertainty about which of the trial arms is most likely to benefit the patient. We sought to estimate the frequency with which equipoise conditions were met in industry-sponsored RCTs in rheumatology, to explore the reasons for any deviations from equipoise, to examine the concept of 'design bias', and to consider alternative ethical formulations that might improve subject safety and autonomy. We studied abstracts accepted for the 2001 American College of Rheumatology meetings that reported RCTs, acknowledged industry sponsorship, and had clinical end-points (n = 45), and examined the proportion of studies that favored the registration or marketing of the sponsor's drug. In every trial (45/45) results were favorable to the sponsor, indicating that results could have been predicted in advance solely by knowledge of sponsorship (P < 0.0001). Equipoise clearly was being systematically violated. Publication bias appeared to be an incomplete explanation for this dramatic result; this bias occurs after a study is completed. Rather, we hypothesize that 'design bias', in which extensive preliminary data are used to design studies with a high likelihood of being positive, is the major cause of the asymmetric results. Design 'bias' occurs before the trial is begun and is inconsistent with the equipoise principle. However, design bias increases scientific efficiency, decreases drug development costs, and limits the number of subjects required, probably reducing aggregate risks to participants. Conceptual and ethical issues were found with the equipoise principle, which encourages performance of negative studies; ignores patient values, patient autonomy, and social benefits; is applied at a conceptually inappropriate decision point (after randomization rather than before); and is in conflict with the Belmont, Nuremberg, and other sets of ethical principles, as well as with US Food and Drug Administration procedures. We propose a principle of 'positive expected outcomes', which informs the assessment that a trial is ethical, together with a restatement of the priority of personal autonomy.

Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

DTIC Science & Technology

2007-05-01

competence of clinical trial staff, and outreach efforts. We have started to geographic, social and physical attributes of the communities surrounding the...aimed at clinical trial sites and that address specific barriers associated with the social or physical environment. 15. SUBJECT TERMS Clinical trials...and availability of trials, patient burden and benefit, site cultural competence, and outreach efforts. We will also examine the social and

Recruitment Strategies and Costs Associated With Enrolling People With Insomnia and High Blood Pressure Into an Online Behavioral Sleep Intervention: A Single-Site Pilot Study.

PubMed

Routledge, Faye S; Davis, Tara D; Dunbar, Sandra B

Recruitment in clinical research is a common challenge and source of study failure. The reporting of recruitment methods and costs in hypertension trials is limited especially for smaller, single-site trials, online intervention trials, and trials using newer online recruitment strategies. The aims of this study are to describe and examine the feasibility of newer online-e-mail recruitment strategies and traditional recruitment strategies used to enroll participants with insomnia and high blood pressure into an online behavioral sleep intervention study (Sleeping for Heart Health). The 16 online-e-mail-based and traditional recruitment strategies used are described. Recruitment strategy feasibility was examined by study interest and enrollee yields, conversion rates, and costs (direct, remuneration, labor, and cost per enrollee). From August 2014 to October 2015, 183 people were screened and 58 (31.7%) enrolled in the study (51.1 ± 12.9 years, 63.8% female, 72.4% African American, 136 ± 12/88 ± 7 mm Hg, 87.9% self-reported hypertension, 67.2% self-reported antihypertensive medication use). The recruitment strategies yielding the highest enrollees were the university hospital phone waiting message system (25.4%), Craigslist (22.4%), and flyers (20.3%) at a per enrollee cost of $42.84, $98.90, and $128.27, respectively. The university hospital phone waiting message system (55.6%) and flyers (54.5%) had the highest interested participant to enrolled participant conversion rate of all recruitment strategies. Approximately 70% of all enrolled participants were recruited from the university hospital phone waiting message system, Craigslist, or flyers. Given the recruitment challenges that most researchers face, we encourage the documenting, assessing, and reporting of detailed recruitment strategies and associated recruitment costs so that other researchers may benefit.

WWC Review of the Report "Closing the Achievement Gap through Modification of Neurocognitive and Neuroendocrine Function: Results from a Cluster Randomized Controlled Trial of an Innovative Approach to the Education of Children in Kindergarten." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

In the 2014 report, "Closing the Achievement Gap Through Modification of Neurocognitive and Neuroendocrine Function: Results from a Cluster Randomized Controlled Trial of an Innovative Approach to the Education of Children in Kindergarten," researchers examined the impacts of "Tools of the Mind" on cognitive and academic…

Problematizing Minority Voices: Intertextuality and Ideology in the Court Reporter's Representation of Rachel Jeantel's Voice in the State of Florida v. George Zimmerman Murder Trial

ERIC Educational Resources Information Center

Sullivan, Grace

2017-01-01

In 2012, Trayvon Martin was killed by George Zimmerman, who, after a month-long highly-publicized trial, was acquitted of second-degree murder. In this study, I examine the testimony of Martin's childhood friend and key witness for the prosecution, Rachel Jeantel. Although Rachel Jeantel was an ear witness to the altercation between Zimmerman and…

A systematic review of studies of web portals for patients with diabetes mellitus.

PubMed

Coughlin, Steven S; Williams, Lovoria B; Hatzigeorgiou, Christos

2017-01-01

Patient web portals are password-protected online websites that offer patients 24-hour access to personal health information from anywhere with an Internet connection. Due to advances in health information technologies, there has been increasing interest among providers and researchers in patient web portals for use by patients with diabetes and other chronic conditions. This article, which is based upon bibliographic searches in PubMed, reviews web portals for patients with diabetes mellitus including patient web portals tethered to electronic medical records and web portals developed specifically for patients with diabetes. Twelve studies of the impact of patient web portals on the management of diabetes patients were identified. Three had a cross-sectional design, 1 employed mixed-methods, one had a matched-control design, 3 had a retrospective cohort design, and 5 were randomized controlled trials. Six (50%) of the studies examined web portals tethered to electronic medical records and the remainder were web portals developed specifically for diabetes patients. The results of this review suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control. However, results from observational studies indicate that many diabetic patients do not take advantage of web portal features such as secure messaging, perhaps because of a lack of internet access or lack of experience in navigating web portal resources. Although results from randomized controlled trials provide stronger evidence of the efficacy of web portal use in improving glycemic control among diabetic patients, the number of trials is small and results from the trials have been mixed. Studies suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control, but negative findings have also been reported. The number of randomized controlled trials that have examined the efficacy of web portal use in improving glycemic control among diabetic patients is still small. Additional research is needed to identify specific portal features that may impact quality of care or improve glycemic control.

Tai Chi Improves Sleep Quality in Healthy Adults and Patients with Chronic Conditions: A Systematic Review and Meta-analysis

PubMed Central

Raman, Gowri; Zhang, Yuan; Minichiello, Vincent J; D'Ambrosio, Carolyn M.; Wang, Chenchen

2017-01-01

Background Physical activity and exercise appear to improve sleep quality. However, the quantitative effects of Tai Chi on sleep quality in the adult population have rarely been examined. We conducted a systematic review and meta-analysis evaluating the effects of Tai Chi on sleep quality in healthy adults and disease populations. Methods Medline, Cochrane Central databases, and review of references were searched through July 31, 2013. English-language studies of all designs evaluating Tai Chi’s effect on sleep outcomes in adults were examined. Data were extracted and verified by 2 reviewers. Extracted information included study setting and design, population characteristics, type and duration of interventions, outcomes, risk of bias and main results. Random effect models meta-analysis was used to assess the magnitude of treatment effect when at least 3 trials reported on the same sleep outcomes. Results Eleven studies (9 randomized and 2 non-randomized trials) totaling 994 subjects published between 2004 and 2012 were identified. All studies except one reported Pittsburg Sleep Quality Index. Nine randomized trials reported that 1.5 to 3 hour each week for a duration of 6 to 24 weeks of Tai Chi significantly improved sleep quality (Effect Size, 0.89; 95% confidence interval [CI], 0.28 to 1.50), in community-dwelling healthy participants and in patients with chronic conditions. Improvement in health outcomes including physical performance, pain reduction, and psychological well-being occurred in the Tai Chi group compared with various controls. Limitations Studies were heterogeneous and some trials were lacking in methodological rigor. Conclusions Tai Chi significantly improved sleep quality in both healthy adults and patients with chronic health conditions, which suggests that Tai Chi may be considered as an alternative behavioral therapy in the treatment of insomnia. High-quality, well-controlled randomized trials are needed to better inform clinical decisions. PMID:28845367

A systematic review of studies of web portals for patients with diabetes mellitus

PubMed Central

Williams, Lovoria B.; Hatzigeorgiou, Christos

2017-01-01

Patient web portals are password-protected online websites that offer patients 24-hour access to personal health information from anywhere with an Internet connection. Due to advances in health information technologies, there has been increasing interest among providers and researchers in patient web portals for use by patients with diabetes and other chronic conditions. This article, which is based upon bibliographic searches in PubMed, reviews web portals for patients with diabetes mellitus including patient web portals tethered to electronic medical records and web portals developed specifically for patients with diabetes. Twelve studies of the impact of patient web portals on the management of diabetes patients were identified. Three had a cross-sectional design, 1 employed mixed-methods, one had a matched-control design, 3 had a retrospective cohort design, and 5 were randomized controlled trials. Six (50%) of the studies examined web portals tethered to electronic medical records and the remainder were web portals developed specifically for diabetes patients. The results of this review suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control. However, results from observational studies indicate that many diabetic patients do not take advantage of web portal features such as secure messaging, perhaps because of a lack of internet access or lack of experience in navigating web portal resources. Although results from randomized controlled trials provide stronger evidence of the efficacy of web portal use in improving glycemic control among diabetic patients, the number of trials is small and results from the trials have been mixed. Studies suggest that secure messaging between adult diabetic patients and their clinician is associated with improved glycemic control, but negative findings have also been reported. The number of randomized controlled trials that have examined the efficacy of web portal use in improving glycemic control among diabetic patients is still small. Additional research is needed to identify specific portal features that may impact quality of care or improve glycemic control. PMID:28736732

Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol

PubMed Central

2012-01-01

Background Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. Methods/Design Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. Discussion Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy outcome. Trial Registration Current Controlled Trials ISRCTN78923965. PMID:22221670

Domestic violence among adolescents in HIV prevention research in Tanzania: Participant experiences and measurement issues

PubMed Central

Baumgartner, Joy Noel; Kaaya, Sylvia; Karungula, Happy; Kaale, Anna; Headley, Jennifer; Tolley, Elizabeth

2014-01-01

Objectives Under-representation of female adolescents in HIV clinical trials may inhibit their access to future prevention technologies. Domestic violence, broadly defined as violence perpetrated by intimate partners and/or family members, may affect trial participation. This study describes violence in the lives of adolescents and young women in Tanzania, explores use of the Women’s Experience with Battering (WEB) Scale to measure battering, and examines the associations between battering and socio-demographic and HIV risk factors. Methods Community formative research (CFR) and a mock clinical trial (MCT) were conducted to examine the challenges of recruiting younger (15-17) versus older (18-21) participants into HIV prevention trials. The CFR included qualitative interviews with 23 participants and there were 135 MCT participants. The WEB was administered in both the CFR and MCT. Results Nineteen CFR participants experienced physical/sexual violence and 17% scored positive for battering. All married participants reported partner-related domestic violence, and half scored positive for battering. Many believed beatings were normal. None of the single participants scored positive on battering, but one-third reported abuse by relatives. Among MCT participants, 15% scored positive for battering; most perpetrators were relatives. Younger participants were more likely to report battering. Conclusions Adolescents experienced high rates of domestic violence and the WEB captured battering from both partners and relatives. The level of familial violence was unexpected and has implications for parental roles in study recruitment. Addressing adolescent abuse in HIV prevention trials and in the general population should be a public health priority. PMID:24740725

Can soy intake affect serum uric acid level? Pooled analysis from two 6-month randomized controlled trials among Chinese postmenopausal women with prediabetes or prehypertension.

PubMed

Liu, Z M; Ho, C S; Chen, Y M; Woo, J

2015-02-01

Hyperuricemia is a recognized risk factor for cardiovascular diseases. Soy foods contain a moderate amount of purine and may predispose to raised serum uric acid (UA). However, no study has examined the long-term effect of soy intake on UA levels. We examined whether consumption of soy foods and isoflavone extracts for 6 months altered serum UA. The analysis included two randomized controlled trials (soy protein trial and whole soy trial) among total 450 postmenopausal women with either prehypertension or prediabetes. We conducted a pooled analysis by combining participants from both the soy flour and soy protein groups (combined soy foods group), participants from both the isoflavone and daidzein groups (combined isoflavone group) and participants from both milk placebo groups. Fasting venous samples were obtained at baseline and the end of the trial for serum UA analysis. In the pooled data, 417 subjects completed the study according to protocol. The baseline serum UA levels were comparable among the three combined groups. There was a lower decrease in UA levels among women in the combined soy foods group compared with women in the other two groups (p = 0.028 and 0.026). The net decrease and % decrease in UA were 14.5 μmol/L (95 % CI 1.93-25.6, p = 0.023) or 4.9 % (95 % CI 1.3-8.5 %, p = 0.023) between the combined soy foods group and placebo group. Among Chinese postmenopausal women with either prehypertension or prediabetes, soy intake did not increase urate levels.

Moderating effects of race in clinical trial participation and outcomes among marijuana-dependent young adults.

PubMed

Montgomery, LaTrice; Petry, Nancy M; Carroll, Kathleen M

2012-12-01

Few studies have examined clinical trial participation rates and treatment outcomes among underserved young adults who are dependent on marijuana, the most commonly abused illicit drug. The present study was a secondary analysis of a trial of court-referred marijuana-dependent young adults (ages 18-25) randomized to one of four treatment conditions: Motivational Enhancement Therapy/Cognitive Behavioral Therapy (MET/CBT), MET/CBT+Contingency Management (CM), Drug Counseling (DC) or DC+CM. African American (N=81) participants were compared to White (N=31) participants with respect to rates of participation in phases of treatment and substance use outcomes. In addition, the interaction of race and treatment condition was examined to ascertain if the interventions yielded different effects based on race. Among those who started treatment, African American young adults were significantly less likely to complete the treatment and posttreatment phases of the clinical trial than their White counterparts. Irrespective of treatment type, substance use outcomes (i.e., percentage of marijuana-negative specimens and longest duration of continuous abstinence) did not vary by race. However, there was a significant interaction effect between treatment type and race; African American young adults did not benefit differentially from any specific type of treatment, but CM was effective in reducing proportion of marijuana positive samples among White young adults. Findings suggest that clinical trial treatment and posttreatment completion rates vary by race in this population, as does response to specific treatment types. More treatment research focusing specifically on African American marijuana-dependent young adults is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A randomized controlled trial of pre-conception treatment for periodontal disease to improve periodontal status during pregnancy and birth outcomes.

PubMed

Jiang, Hong; Xiong, Xu; Su, Yi; Zhang, Yiming; Wu, Hongqiao; Jiang, Zhijun; Qian, Xu

2013-12-09

Evidence has suggested that periodontal disease is associated with an increased risk of various adverse pregnancy and birth outcomes. However, several large clinical randomized controlled trials failed to demonstrate periodontal therapy during pregnancy reduced the incidence of adverse pregnancy and birth outcomes. It has been suggested that the pre-conception period may be an optimal period for periodontal disease treatment rather than during pregnancy. To date, no randomized controlled trial (RCT) has examined if treating periodontal disease before pregnancy reduces adverse birth outcomes. This study aims to examine if the pre-conception treatment of periodontal disease will lead to improved periodontal status during late pregnancy and subsequent birth outcomes. A sample of 470 (235 in each arm of the study) pre-conception women who plan to conceive within one year and with periodontal disease will be recruited for the study. All participants will be randomly allocated to the intervention or control group. The intervention group will receive free therapy including dental scaling and root planning (the standard therapy), supragingival prophylaxis, and oral hygiene education. The control group will only receive supragingival prophylaxis and oral hygiene education. Women will be followed throughout their pregnancy and then to childbirth. The main outcomes include periodontal disease status in late pregnancy and birth outcomes measured such as mean birth weight (grams), and mean gestational age (weeks). Periodontal disease will be diagnosed through a dental examination by measuring probing depth, clinical attachment loss and percentage of bleeding on probing (BOP) between gestational age of 32 and 36 weeks. Local and systemic inflammatory mediators are also included as main outcomes. This will be the first RCT to test whether treating periodontal disease among pre-conception women reduces periodontal disease during pregnancy and prevents adverse birth outcomes. If the effect of pre-pregnancy periodontal treatment is confirmed, this intervention could be recommended for application in low- or middle-income countries to improve both oral health and maternal and child health. This trial is registered with Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-12001913.

Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials

PubMed Central

Goodman, Phyllis J.; Till, Cathee; Schenk, Jeannette M.; Lucia, M. Scott; Thompson, Ian M.

2016-01-01

Purpose To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor–prostate cancer associations. Patients and Methods Men who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-of-study biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts. Results Men 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index (≥ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostate-specific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black (v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%. Conclusion Among screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts. PMID:27998216

Culturally-Tailored Smoking Cessation for American Indians: Study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Cigarette smoking is the number one cause of preventable death among American Indian and Alaska Natives, AI/ANs. Two out of every five AI/AN will die from tobacco-related diseases if the current smoking rates of AI/ANs (40.8%) persist. Currently, there is no proven, effective culturally-tailored smoking cessation program designed specifically for a heterogeneous population of AI. The primary aim of this group randomized clinical trial is to test the efficacy of "All Nations Breath of Life" (ANBL) program compared to a non-tailored "Current Best Practices" smoking cessation program among AI smokers. Methods We will randomize 56 groups (8 smokers per group) to the tailored program or non-tailored program for a total sample size of 448 American Indian smokers. All participants in the proposed study will be offered pharmacotherapy, regardless of group assignment. This study is the first controlled trial to examine the efficacy of a culturally-tailored smoking cessation program for American Indians. If the intervention is successful, the potential health impact is significant because the prevalence of smoking is the highest in this population. Trial Registration ClinicalTrials.gov: NCT01106456 PMID:21592347

Does the Effort of Processing Potential Incentives Influence the Adaption of Context Updating in Older Adults?

PubMed Central

Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K.

2017-01-01

A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults’ ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65–76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69–78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing. PMID:29170649

Does the Effort of Processing Potential Incentives Influence the Adaption of Context Updating in Older Adults?

PubMed

Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K

2017-01-01

A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults' ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65-76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69-78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing.

Causal assessment of surrogacy in a meta-analysis of colorectal cancer trials

PubMed Central

Li, Yun; Taylor, Jeremy M.G.; Elliott, Michael R.; Sargent, Daniel J.

2011-01-01

When the true end points (T) are difficult or costly to measure, surrogate markers (S) are often collected in clinical trials to help predict the effect of the treatment (Z). There is great interest in understanding the relationship among S, T, and Z. A principal stratification (PS) framework has been proposed by Frangakis and Rubin (2002) to study their causal associations. In this paper, we extend the framework to a multiple trial setting and propose a Bayesian hierarchical PS model to assess surrogacy. We apply the method to data from a large collection of colon cancer trials in which S and T are binary. We obtain the trial-specific causal measures among S, T, and Z, as well as their overall population-level counterparts that are invariant across trials. The method allows for information sharing across trials and reduces the nonidentifiability problem. We examine the frequentist properties of our model estimates and the impact of the monotonicity assumption using simulations. We also illustrate the challenges in evaluating surrogacy in the counterfactual framework that result from nonidentifiability. PMID:21252079

Feasibility and acceptability of the DSM-5 Field Trial procedures in the Johns Hopkins Community Psychiatry Programs†

PubMed Central

Clarke, Diana E.; Wilcox, Holly C.; Miller, Leslie; Cullen, Bernadette; Gerring, Joan; Greiner, Lisa H.; Newcomer, Alison; Mckitty, Mellisha V.; Regier, Darrel A.; Narrow, William E.

2014-01-01

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) contains criteria for psychiatric diagnoses that reflect advances in the science and conceptualization of mental disorders and address the needs of clinicians. DSM-5 also recommends research on dimensional measures of cross-cutting symptoms and diagnostic severity, which are expected to better capture patients’ experiences with mental disorders. Prior to its May 2013 release, the American Psychiatric Association (APA) conducted field trials to examine the feasibility, clinical utility, reliability, and where possible, the validity of proposed DSM-5 diagnostic criteria and dimensional measures. The methods and measures proposed for the DSM-5 field trials were pilot tested in adult and child/adolescent clinical samples, with the goal to identify and correct design and procedural problems with the proposed methods before resources were expended for the larger DSM-5 Field Trials. Results allowed for the refinement of the protocols, procedures, and measures, which facilitated recruitment, implementation, and completion of the DSM-5 Field Trials. These results highlight the benefits of pilot studies in planning large multisite studies. PMID:24615761

Goal-setting, self-efficacy, and memory performance in older and younger adults.

PubMed

West, R L; Thorn, R M

2001-01-01

Research in field and laboratory settings has shown that goals lead to improved self-efficacy and performance, especially when individuals also receive positive feedback. The present study extended goal-setting theory to examine self-set goals and feedback in relation to younger and older adults' memory performance and self-efficacy. Following a baseline recall trial, participants completed three shopping list recall trials. Half of the participants were instructed to set goals for the three experimental trials, and half in each goal condition received performance feedback after each trial. Young adults' self-efficacy, clustering, and recall exceeded that of older adults. Goal setting increased self-efficacy for younger but not older adults, and it did not affect performance. Younger adults and participants in the feedback condition increased their goals across trials, as did participants for whom feedback indicated success. These data provide a first look at the motivational impact of feedback and self-set recall goals in memory aging. Additional study is needed to understand the interactive effects of type of feedback, memory task difficulty, and type of goal setting at different ages.

The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

PubMed

Lemaire, François; Marchenay, Brigitte; Chassany, Olivier; Barthélémy, Philippe; Bouzzagou, Mohamed; Comet, Denis; Delval, Cécile; Dubray, Claude; Fouret, Cécile; Frija-Orvoen, Elisabeth; Gambotti, Laetitia; Lamarque, Véronique; d'Orsay, Geneviève; Plattner, Valérie; Sibenaler, Claire; Roux, Jacques; Thoby, Frédérique

2015-01-01

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency. © 2015 Société Française de Pharmacologie et de Thérapeutique.

“Ready-to-Recruit” or “Ready-to-Consent” Populations?: Informed Consent and the Limits of Subject Autonomy

PubMed Central

Fisher, Jill A.

2011-01-01

This paper queries the pharmaceutical industry’s concept of “ready-to-recruit” populations by examining its recruitment strategies for clinical trials and the types of human subjects who participate in these drug studies. The argument is that the pharmaceutical industry has profited from a system comprised of what can more aptly be characterized as ready-to-consent populations, meaning populations who do not have better alternatives than participation in clinical trials. Further, through qualitative research, this paper aims to highlight some of the limitations of current U.S. federal regulation and to show how these limits signal problems that are not normally discussed in the medical ethics literature about research on human subjects. It does this by examining the impotence of informed consent – both as a concept and as a practice – in light of recruitment strategies and the structural reasons motivating individuals to participate in clinical trials. PMID:21359125

Comparing the effect of a decision aid plus patient navigation with usual care on colorectal cancer screening completion in vulnerable populations: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Screening can reduce colorectal cancer (CRC) incidence and mortality. However, screening is underutilized in vulnerable patient populations, particularly among Latinos. Patient-directed decision aids can increase CRC screening knowledge, self-efficacy, and intent; however, their effect on actual screening test completion tends to be modest. This is probably because decision aids do not address some of the patient-specific barriers that prevent successful completion of CRC screening in these populations. These individual barriers might be addressed though patient navigation interventions. This study will test a combined decision aid and patient navigator intervention on screening completion in diverse populations of vulnerable primary care patients. Methods/Design We will conduct a multisite, randomized controlled trial with patient-level randomization. Planned enrollment is 300 patients aged 50 to 75 years at average CRC risk presenting for appointments at two primary clinics in North Carolina and New Mexico. Intervention participants will view a video decision aid immediately before the clinic visit. The 14 to 16 minute video presents information about fecal occult blood tests and colonoscopy and will be viewed on a portable computer tablet in English or Spanish. Clinic-based patient navigators are bilingual and bicultural and will provide both face-to-face and telephone-based navigation. Control participants will view an unrelated food safety video and receive usual care. The primary outcome is completion of a CRC screening test at six months. Planned subgroup analyses include examining intervention effectiveness in Latinos, who will be oversampled. Secondarily, the trial will evaluate the intervention effects on knowledge of CRC screening, self-efficacy, intent, and patient-provider communication. The study will also examine whether patient ethnicity, acculturation, language preference, or health insurance status moderate the intervention effect on CRC screening. Discussion This pragmatic randomized controlled trial will test a combined decision aid and patient navigator intervention targeting CRC screening completion. Findings from this trial may inform future interventions and implementation policies designed to promote CRC screening in vulnerable patient populations and to reduce screening disparities. Clinical trial registration ClinicalTrials.gov NCT02054598. PMID:25004983

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics and their Environment

DTIC Science & Technology

2012-07-01

sites to assess their discussions with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about...with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about such trials, and barriers to and...calculated and compared across race/ethnicity. Examination of major outcomes included willingness to participate in, knowledge of, and attitudes towards

The effects of psychological treatment of maternal depression on children and parental functioning: a meta-analysis.

PubMed

Cuijpers, Pim; Weitz, Erica; Karyotaki, Eirini; Garber, Judy; Andersson, Gerhard

2015-02-01

Successful treatment of parental depression may have a positive effect on the functioning and psychopathology of their children. We conducted a meta-analysis to examine the effects of psychotherapy for depressed mothers on their children and parental functioning. We used a database of randomized controlled trials examining the effects of psychotherapy for adult depression and selected trials comparing psychotherapy and control conditions in depressed mothers and reporting outcomes in their children and parental functioning. Nine studies were included. The quality of these studies was not optimal and the outcome instruments differed considerably from each other. The therapies resulted in significantly decreased levels of depression (g = 0.66) in the mothers. In the seven studies that reported outcomes on the mental health of children, a significant effect size was also found (g = 0.40). The eight studies examining mother-child interactions resulted in a significant effect size of g = 0.35, and the five studies examining parenting/marital distress had a pooled effect size of g = 0.67. We found that psychotherapy leads to decreased levels of depression in depressed mothers and also found indications that psychotherapy may have a positive effect on the mental health of their children and parenting/marital distress. However, more high-quality research is needed before a definite answer can be given.

The reduction of intoxication and disorder in premises licensed to serve alcohol: An exploratory randomised controlled trial

PubMed Central

2010-01-01

Background Licensed premises offer a valuable point of intervention to reduce alcohol-related harm. Objective To describe the research design for an exploratory trial examining the feasibility and acceptability of a premises-level intervention designed to reduce severe intoxication and related disorder. The study also aims to assess the feasibility of a potential future large scale effectiveness trial and provide information on key trial design parameters including inclusion criteria, premises recruitment methods, strategies to implement the intervention and trial design, outcome measures, data collection methods and intra-cluster correlations. Design A randomised controlled trial in licensed premises that had experienced at least one assault in the year preceding the intervention, documented in police or hospital Emergency Department (ED) records. Premises were recruited from four study areas by piloting four recruitment strategies of varying intensity. Thirty two licensed premises were grouped into matched pairs to reduce potential bias and randomly allocated to the control or intervention condition. The study included a nested process evaluation to provide information on intervention acceptability and implementation. Outcome measures included police-recorded violent incidents, assault-related attendances at each premises' local ED and patron Breath Alcohol Concentration assessed on exiting and entering study premises. Results The most successful recruitment method involved local police licensing officers and yielded a 100% success rate. Police-records of violence provided the most appropriate source of data about disorder at the premises level. Conclusion The methodology of an exploratory trial is presented and despite challenges presented by the study environment it is argued an exploratory trial is warranted. Initial investigations in recruitment methods suggest that study premises should be recruited with the assistance of police officers. Police data were of sufficient quality to identify disorder and street surveys are a feasible method for measuring intoxication at the individual level. Trial registration UKCRN 7090; ISRCTN: 80875696 Funding Medical Research Council (G0701758) to Simon Moore, Simon Murphy, Laurence Moore and Jonathan Shepherd PMID:20946634

Reproducibility of a silicone-based test food to masticatory performance evaluation by different sieve methods.

PubMed

Sánchez-Ayala, Alfonso; Vilanova, Larissa Soares Reis; Costa, Marina Abrantes; Farias-Neto, Arcelino

2014-01-01

The aim of this study was to evaluate the reproducibility of the condensation silicone Optosil Comfort® as an artificial test food for masticatory performance evaluation. Twenty dentate subjects with mean age of 23.3±0.7 years were selected. Masticatory performance was evaluated using the simple (MPI), the double (IME) and the multiple sieve methods. Trials were carried out five times by three examiners: three times by the first, and once by the second and third examiners. Friedman's test was used to find the differences among time trials. Reproducibility was determined by the intra-class correlation (ICC) test (α=0.05). No differences among time trials were found, except for MPI-4 mm (p=0.022) from the first examiner results. The intra-examiner reproducibility (ICC) of almost all data was high (ICC≥0.92, p<0.001), being moderate only for MPI-0.50 mm (ICC=0.89, p<0.001). The inter-examiner reproducibility was high (ICC>0.93, p<0.001) for all results. For the multiple sieve method, the average mean of absolute difference from repeated measurements were lower than 1 mm. This trend was observed only from MPI-0.50 to MPI-1.4 for the single sieve method, and from IME-0.71/0.50 to IME-1.40/1.00 for the double sieve method. The results suggest that regardless of the method used, the reproducibility of Optosil Comfort® is high.

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

Ketamine as an adjuvant to opioids for cancer pain.

PubMed

Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

2017-06-28

This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity.Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity.The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial.For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear to have clinical benefit and may be associated with serious adverse events. More randomised controlled trials (RCTs) examining specific low-dose ketamine clinical regimens in current use are needed.

The Effectiveness Of Social Media (Facebook) Compared With More Traditional Advertising Methods for Recruiting Eligible Participants To Health Research Studies: A Randomized, Controlled Clinical Trial

PubMed Central

Thow, Megan; Ferguson, Stuart G

2016-01-01

Background Recruiting participants for research studies can be difficult and costly. The popularity of social media platforms (eg, Facebook) has seen corresponding growth in the number of researchers turning to social networking sites and their embedded advertising frameworks to locate eligible participants for studies. Compared with traditional recruitment strategies such as print media, social media advertising has been shown to be favorable in terms of its reach (especially with hard-to-reach populations), cost effectiveness, and usability. However, to date, no studies have examined how participants recruited via social media progress through a study compared with those recruited using more traditional recruitment strategies. Objectives (1) Examine whether visiting the study website prior to being contacted by researchers creates self-screened participants who are more likely to progress through all study phases (eligible, enrolled, completed); (2) compare conversion percentages and cost effectiveness of each recruitment method at each study phase; and, (3) compare demographic and smoking characteristics of participants recruited through each strategy to determine if they attract similar samples. Methods Participants recruited to a smoking cessation clinical trial were grouped by how they had become aware of the study: via social media (Facebook) or traditional media (eg, newspaper, flyers, radio, word of mouth). Groups were compared based on throughput data (conversion percentages and cost) as well as demographic and smoking characteristics. Results Visiting the study website did not result in individuals who were more likely to be eligible for (P=.24), enroll in (P=.20), or complete (P=.25) the study. While using social media was more cost effective than traditional methods when we examined earlier endpoints of the recruitment process (cost to obtain a screened respondent: AUD $22.73 vs $29.35; cost to obtain an eligible respondent: $37.56 vs $44.77), it was less cost effective in later endpoints (cost per enrolled participant: $56.34 vs $52.33; cost per completed participant: $103.66 vs $80.43). Participants recruited via social media were more likely to be younger (P=.001) and less confident in their quit attempts (P=.004) compared to those recruited via traditional methods. Conclusions Our study suggests that while social media advertising may be effective in generating interest from potential participants, this strategy’s ability to attract conscientious recruits is more questionable. Researchers considering using online resources (eg, social media advertising, matrix codes) should consider including prescreening questions to promote conversion percentages. Ultimately, researchers seeking to maximize their recruitment budget should consider using a combination of advertising strategies. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN 12614000329662; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365947l (Archived by WebCite at http://www.webcitation.org/6jc6zXWZI) PMID:27511829

Interventions for increasing fruit and vegetable consumption in children aged 5 years and under

PubMed Central

Wolfenden, Luke; Wyse, Rebecca J; Britton, Ben I; Campbell, Karen J; Hodder, Rebecca K; Stacey, Fiona G; McElduff, Patrick; James, Erica L

2014-01-01

Background Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases including cardiovascular disease. Objectives To assess the effectiveness, cost-effectiveness and associated adverse events of interventions designed to increase the consumption of fruit and/or vegetables amongst children aged five years and under. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 2, 2010, MEDLINE (1950 to 2010 April week 4), EMBASE (1947 to 2010 week 18), CINAHL (up to 12 May 2010), PsycINFO (up to 12 May 2010) and Proquest Dissertations and Theses (up to February 2011) were searched to identify eligible trials, as well as electronic trial registers (also up to February 2011). The reference lists of included trials were reviewed and handsearches of three international nutrition journals were also performed. Authors of all included trials were contacted in order to identify further potentially relevant trials. Selection criteria We included randomised controlled trials (RCTs), including cluster-randomised controlled trials, of any intervention primarily targeting fruit and/or vegetable consumption among children aged five years and under and incorporating a biochemical or dietary assessment of fruit and/or vegetable consumption. Two review authors independently screened the titles and abstracts of identified papers. A third review author with expertise in review methodology resolved any disagreements regarding study eligibility. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of the included studies. A third reviewer resolved disagreements between review authors. Fixed-effect models were used to perform meta-analysis for the primary review outcomes where a sufficient number of trials with suitable data and homogeneity were identified. Main results Five trials, with 13 trial arms and 3967 participants were included in the review. Two trials examined the impact of specific feeding practices (e.g. repeated food exposure) in increasing child intake of a target vegetable. Two trials assessed the effectiveness of home visiting programs implemented in disadvantaged communities and one trial investigated the effect of a preschool-based intervention in increasing child fruit and vegetable intake. Risk of bias of included studies was low although three of the five trials were judged to be at high risk of performance bias. Meta-analysis of two trials examining repeated food exposure versus a no intervention comparison found no significant difference in target vegetable consumption in the short term (mean difference (MD) 1.37, 95% confidence interval (CI) −2.78 to 5.52). Coupling repeated food exposure with a tangible non-food or social reward, was effective in increasing targeted vegetable consumption in the short term based on one trial. Home visiting programs provided to disadvantaged groups did not significantly increase overall fruit intake in the short term (standardised mean difference (SMD) 0.01, 95% CI −0.09 to 0.11). Similarly, a multi-component preschool-based intervention failed to significantly increase child consumption of vegetables, but did report a small significant increase in mean child consumption of fruit, six months following baseline assessment. None of the trials investigated intervention cost-effectiveness or reported information regarding any adverse events or unintended adverse consequences of the intervention. Authors’ conclusions Despite the importance of encouraging fruit and vegetable consumption among children aged five years and under, this review identified few randomised controlled trials investigating interventions to achieve this. PMID:23152262

Treating co-morbid chronic medical conditions and anxiety/depression.

PubMed

Cimpean, D; Drake, R E

2011-06-01

This systematic review examines interventions for care of people with co-morbid chronic medical illness and anxiety/depression disorders--a group with high risks for morbidity and mortality. Systematic search of Medline 1995 to January 2011 for randomized controlled trials of treatment interventions designed for adult outpatients with diagnosed chronic medical illness (diabetes mellitus, cardiovascular disorders, and chronic respiratory disorders) and anxiety/depression disorders. Six trials studied complex interventions based on the chronic care model, and eight trials studied psychosocial interventions. Most interventions addressed the mental health aspect of the co-morbidity and showed improvements in anxiety/depression but not in the co-morbid medical disorder. Further research might focus on interventions integrating mental health treatment with enhanced medical care components, incorporating shared-decision making and information technology advances.

Exercise and mental health: a review.

PubMed

Glenister, D

1996-02-01

With the advent of programmes to raise the level of fitness in the general population, and alliances between primary health care and community leisure services, the potential of exercise in promoting mental as well as physical health deserves investigation. In contrast to USA and continental Europe, there is a paucity of British research studies systematically exploring the mental health benefits of exercise. The recent rapid growth of exercise prescription among general practitioners presents an opportunity for future research. This review of eleven randomised control trials (RCTs) suggests a causal relationship between exercise and mental health based upon studies in various settings. The methodological difficulties associated with randomised control trials of psycho-social interventions are discussed. The value of future randomised control trials which incorporate examination of perceived acceptability and health economics is indicated.

The ClinicalTrials.gov results database--update and key issues.

PubMed

Zarin, Deborah A; Tse, Tony; Williams, Rebecca J; Califf, Robert M; Ide, Nicholas C

2011-03-03

The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications. PMID:23335556

The effects of general pretrial publicity on juror decisions: an examination of moderators and mediating mechanisms.

PubMed

Kovera, Margaret Bull

2002-02-01

Two studies examined three moderators (gender, attitudes, and media slant) and four mediators (accessibility, evidence importance, evidence plausibility, and standards of guilt) of general pretrial publicity's influence on juror decisions. In Study 1, participants who watched a prodefense rape story were more likely to report that they would need more inculpatory evidence to convict a defendant of rape than were participants who watched a proprosecution rape story. In Study 2, participants watched news stories, one of which was a proprosecution rape story, a prodefense rape story, or a nonrape story. In an ostensibly unrelated study, participants indicated their attitudes toward rape, watched a rape trial, and provided trial and witness ratings. Accessibility did not mediate the media effects on participants' judgments of rape importance; however, attitudes moderated media effects. Rape news influenced juror ratings of the importance of evidence about the complainant's behavior. Finally, media altered the standards participants used to determine defendant guilt. Implications for understanding the mechanisms responsible for pretrial publicity effects are discussed.

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.

Strategies for enhancing the implementation of school-based policies or practices targeting risk factors for chronic disease.

PubMed

Wolfenden, Luke; Nathan, Nicole K; Sutherland, Rachel; Yoong, Sze Lin; Hodder, Rebecca K; Wyse, Rebecca J; Delaney, Tessa; Grady, Alice; Fielding, Alison; Tzelepis, Flora; Clinton-McHarg, Tara; Parmenter, Benjamin; Butler, Peter; Wiggers, John; Bauman, Adrian; Milat, Andrew; Booth, Debbie; Williams, Christopher M

2017-11-29

A number of school-based policies or practices have been found to be effective in improving child diet and physical activity, and preventing excessive weight gain, tobacco or harmful alcohol use. Schools, however, frequently fail to implement such evidence-based interventions. The primary aims of the review are to examine the effectiveness of strategies aiming to improve the implementation of school-based policies, programs or practices to address child diet, physical activity, obesity, tobacco or alcohol use.Secondary objectives of the review are to: Examine the effectiveness of implementation strategies on health behaviour (e.g. fruit and vegetable consumption) and anthropometric outcomes (e.g. BMI, weight); describe the impact of such strategies on the knowledge, skills or attitudes of school staff involved in implementing health-promoting policies, programs or practices; describe the cost or cost-effectiveness of such strategies; and describe any unintended adverse effects of strategies on schools, school staff or children. All electronic databases were searched on 16 July 2017 for studies published up to 31 August 2016. We searched the following electronic databases: Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; Embase Classic and Embase; PsycINFO; Education Resource Information Center (ERIC); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Dissertations and Theses; and SCOPUS. We screened reference lists of all included trials for citations of other potentially relevant trials. We handsearched all publications between 2011 and 2016 in two specialty journals (Implementation Science and Journal of Translational Behavioral Medicine) and conducted searches of the WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/) as well as the US National Institutes of Health registry (https://clinicaltrials.gov). We consulted with experts in the field to identify other relevant research. 'Implementation' was defined as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised or non-randomised) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by school staff to 'no intervention', 'usual' practice or a different implementation strategy. Citation screening, data extraction and assessment of risk of bias was performed by review authors in pairs. Disagreements between review authors were resolved via consensus, or if required, by a third author. Considerable trial heterogeneity precluded meta-analysis. We narratively synthesised trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We included 27 trials, 18 of which were conducted in the USA. Nineteen studies employed randomised controlled trial (RCT) designs. Fifteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of risk factors. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials examined multi-strategic implementation strategies and no two trials examined the same combinations of implementation strategies. The most common implementation strategies included educational materials, educational outreach and educational meetings. For all outcomes, the overall quality of evidence was very low and the risk of bias was high for the majority of trials for detection and performance bias.Among 13 trials reporting dichotomous implementation outcomes-the proportion of schools or school staff (e.g. classes) implementing a targeted policy or practice-the median unadjusted (improvement) effect sizes ranged from 8.5% to 66.6%. Of seven trials reporting the percentage of a practice, program or policy that had been implemented, the median unadjusted effect (improvement), relative to the control ranged from -8% to 43%. The effect, relative to control, reported in two trials assessing the impact of implementation strategies on the time per week teachers spent delivering targeted policies or practices ranged from 26.6 to 54.9 minutes per week. Among trials reporting other continuous implementation outcomes, findings were mixed. Four trials were conducted of strategies that sought to achieve implementation 'at scale', that is, across samples of at least 50 schools, of which improvements in implementation were reported in three trials.The impact of interventions on student health behaviour or weight status were mixed. Three of the eight trials with physical activity outcomes reported no significant improvements. Two trials reported reductions in tobacco use among intervention relative to control. Seven of nine trials reported no between-group differences on student overweight, obesity or adiposity. Positive improvements in child dietary intake were generally reported among trials reporting these outcomes. Three trials assessed the impact of implementation strategies on the attitudes of school staff and found mixed effects. Two trials specified in the study methods an assessment of potential unintended adverse effects, of which, they reported none. One trial reported implementation support did not significantly increase school revenue or expenses and another, conducted a formal economic evaluation, reporting the intervention to be cost-effective. Trial heterogeneity, and the lack of consistent terminology describing implementation strategies, were important limitations of the review. Given the very low quality of the available evidence, it is uncertain whether the strategies tested improve implementation of the targeted school-based policies or practices, student health behaviours, or the knowledge or attitudes of school staff. It is also uncertain if strategies to improve implementation are cost-effective or if they result in unintended adverse consequences. Further research is required to guide efforts to facilitate the translation of evidence into practice in this setting.

Language of the Legal Process: An Analysis of Interactions in the "Syariah" Court

ERIC Educational Resources Information Center

Hashim, Azirah; Hassan, Norizah

2011-01-01

This study examines interactions from trials in the Syariah court in Malaysia. It focuses on the types of questioning, the choice of language and the linguistic resources employed in this particular context. In the discourse of law, questioning has been a prominent concern particularly in cross-examination and can be considered one of the key…

Public titles of clinical trials should have ethics review.

PubMed

Saenz, Carla; Reveiz, Ludovic; Tisdale, John F

2015-09-01

A key aspect to guarantee that research with human subjects is ethical is being overlooked. Ethics review committees invest great effort examining the informed consent documents of research protocols to ensure that potential participants can provide consent validly and are not deluded into thinking that the experimental intervention they may sign up for is already known to be therapeutic. However, these efforts to avoid what is called the "therapeutic misconception" might be in vain if the title with which the studies are being introduced to the potential participants escapes ethics review. Research participants might be deceived by clinical trials entitled "novel therapy" when the point of the trial is precisely to find out whether the intervention at stake is therapeutic or not. Providing potential research participants with such misleading information hampers their ability to make informed decisions. The well-established scrutiny that ethics review committees exercise with regard to consent forms is limited if the registration of clinical trials, for which a public title is chosen, constitutes a process that is independent from the ethics review. In this article, we examine this problem, assess recent measures to integrate clinical trial registration with ethics review processes, and provide specific recommendations to solve the problem and ultimately enhance the accountability, transparency, and ethics of research with human subjects. Copyright © 2015 Pan American Health Organization. Published by Elsevier Inc. All rights reserved.

Clinical trial designs to obtain marketing authorization of drugs for haematological malignancy in Japan, the EU and the US.

PubMed

Nagai, Sumimasa; Ozawa, Keiya

2016-07-01

Differences in regulatory actions between Japan, the European Union (EU) and the United States (US) regarding the approval date and primary endpoints of pivotal trials have never been analysed comprehensively. This study aimed to examine such differences in haematological malignancy indications not only in applications for new molecular entity agents but also in supplemental applications for additional indications. A total of 101 haematological malignancy indications were examined for 58 drugs. Only 30 indications were approved by the regulatory agencies of all three regions with 25, 9 and 67 indications being first approved in Japan, the EU and the US, respectively. Regarding the 18 indications approved only in the US, 13 were approved based on results of single-arm trials. The approval of all nine indications approved first in the EU was based on results of comparative trials. The primary endpoints were different between the EU and the US in 4 of 49 indications approved by both regulatory agencies, all of which were approved earlier in the US than in the EU. This analysis shows that the US Food and Drug Administration has taken the most active attitude to acceptance of surrogate endpoints in single-arm trials. Therefore, not only shorter review time but also this attitude may lead to earlier approval in US. © 2016 John Wiley & Sons Ltd.

Effect of an exercise training intervention with resistance bands on blood cell counts during chemotherapy for lung cancer: a pilot randomized controlled trial.

PubMed

Karvinen, Kristina H; Esposito, David; Raedeke, Thomas D; Vick, Joshua; Walker, Paul R

2014-01-01

Chemotherapy for lung cancer can have a detrimental effect on white blood cell (WBC) and red blood cell (RBC) counts. Physical exercise may have a role in improving WBCs and RBCs, although few studies have examined cancer patients receiving adjuvant therapies. The purpose of this pilot trial was to examine the effects of an exercise intervention utilizing resistance bands on WBCs and RBCs in lung cancer patients receiving curative intent chemotherapy. A sample of lung cancer patients scheduled for curative intent chemotherapy was randomly assigned to the exercise intervention (EX) condition or usual care (UC) condition. The EX condition participated in a three times weekly exercise program using resistance bands for the duration of chemotherapy. A total of 14 lung cancer patients completed the trial. EX condition participants completed 79% of planned exercise sessions. The EX condition was able to maintain WBCs over the course of the intervention compared to declines in the UC condition (p = .008; d = 1.68). There were no significant differences in change scores in RBCs. Exercise with resistance bands may help attenuate declines in WBCs in lung cancer patients receiving curative intent chemotherapy. Larger trials are warranted to validate these findings. Ultimately these findings could be informative for the development of supportive care strategies for lung cancer patients receiving chemotherapy. Clinical Trials Registration #: NCT01130714.