Effect of physical activity on frailty and associated negative outcomes: the LIFE randomized trial

USDA-ARS?s Scientific Manuscript database

Background: Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large, long-term, randomized trials are lacking. Objective: To determine whether a long-term structured moderate-intensity physical activity (PA) p...

An Overview of Randomization and Minimization Programs for Randomized Clinical Trials

PubMed Central

Saghaei, Mahmoud

2011-01-01

Randomization is an essential component of sound clinical trials, which prevents selection biases and helps in blinding the allocations. Randomization is a process by which subsequent subjects are enrolled into trial groups only by chance, which essentially eliminates selection biases. A serious consequence of randomization is severe imbalance among the treatment groups with respect to some prognostic factors, which invalidate the trial results or necessitate complex and usually unreliable secondary analysis to eradicate the source of imbalances. Minimization on the other hand tends to allocate in such a way as to minimize the differences among groups, with respect to prognostic factors. Pure minimization is therefore completely deterministic, that is, one can predict the allocation of the next subject by knowing the factor levels of a previously enrolled subject and having the properties of the next subject. To eliminate the predictability of randomization, it is necessary to include some elements of randomness in the minimization algorithms. In this article brief descriptions of randomization and minimization are presented followed by introducing selected randomization and minimization programs. PMID:22606659

Run-Reversal Equilibrium for Clinical Trial Randomization

PubMed Central

Grant, William C.

2015-01-01

In this paper, we describe a new restricted randomization method called run-reversal equilibrium (RRE), which is a Nash equilibrium of a game where (1) the clinical trial statistician chooses a sequence of medical treatments, and (2) clinical investigators make treatment predictions. RRE randomization counteracts how each investigator could observe treatment histories in order to forecast upcoming treatments. Computation of a run-reversal equilibrium reflects how the treatment history at a particular site is imperfectly correlated with the treatment imbalance for the overall trial. An attractive feature of RRE randomization is that treatment imbalance follows a random walk at each site, while treatment balance is tightly constrained and regularly restored for the overall trial. Less predictable and therefore more scientifically valid experiments can be facilitated by run-reversal equilibrium for multi-site clinical trials. PMID:26079608

Mediterranean dietary pattern and depression: the PREDIMED randomized trial

PubMed Central

2013-01-01

Background A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention. Methods This was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevención con Dieta Mediterránea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression. Results We identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98). Conclusions The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2. Trial registration This trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639 PMID:24229349

A randomized trial comparing concise and standard consent forms in the START trial

PubMed Central

Touloumi, Giota; Walker, A. Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G.; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

2017-01-01

Background Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. Methods We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). Results 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. Conclusions An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Trial registration Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008

Asthma randomized trial of indoor wood smoke (ARTIS): Rationale and Methods

PubMed Central

Noonan, Curtis W.; Ward, Tony J.

2012-01-01

Background Particulate matter (PM) exposures have been linked with poor respiratory health outcomes, especially among susceptible populations such as asthmatic children. Smoke from biomass combustion for residential home heating is an important source of PM in many rural or peri-urban areas in the United States. Aim To assess the efficacy of residential interventions that reduce indoor PM exposure from wood stoves and to quantify the corresponding improvements in quality of life and health outcomes for asthmatic children. Design The Asthma Randomized Trial of Indoor wood Smoke (ARTIS) study is an in-home intervention study of susceptible children exposed to biomass combustion smoke. Children, ages 7 to 17, with persistent asthma and living in homes that heat with wood stoves were recruited for this three arm randomized placebo-controlled trial. Two household-level intervention strategies, wood stove replacement and air filters, were compared to a sham air filter placebo. Improvement in quality of life of asthmatic children was the primary outcomes. Secondary asthma-related health outcomes included peak expiratory flow (PEF) and forced expiratory volume in first second (FEV1), biomarkers in exhaled breath condensate, and frequency of asthma symptoms, medication usage, and healthcare utilization. Exposure outcomes included indoor and outdoor PM2.5 mass, particle counts of several size fractions, and carbon monoxide. Discussion To our knowledge, this was the first randomized trial in the US to utilize interventions targeting residential wood stoves to assess the impact on indoor PM and health outcomes in a susceptible population. Trial registration ClincialTrials.gov NCT00807183. PMID:22735495

Methodological survey of designed uneven randomization trials (DU-RANDOM): a protocol.

PubMed

Wu, Darong; Akl, Elie A; Guyatt, Gordon H; Devereaux, Philip J; Brignardello-Petersen, Romina; Prediger, Barbara; Patel, Krupesh; Patel, Namrata; Lu, Taoying; Zhang, Yuan; Falavigna, Maicon; Santesso, Nancy; Mustafa, Reem A; Zhou, Qi; Briel, Matthias; Schünemann, Holger J

2014-01-23

Although even randomization (that is, approximately 1:1 randomization ratio in study arms) provides the greatest statistical power, designed uneven randomization (DUR), (for example, 1:2 or 1:3) is used to increase participation rates. Until now, no convincing data exists addressing the impact of DUR on participation rates in trials. The objective of this study is to evaluate the epidemiology and to explore factors associated with DUR. We will search for reports of RCTs published within two years in 25 general medical journals with the highest impact factor according to the Journal Citation Report (JCR)-2010. Teams of two reviewers will determine eligibility and extract relevant information from eligible RCTs in duplicate and using standardized forms. We will report the prevalence of DUR trials, the reported reasons for using DUR, and perform a linear regression analysis to estimate the association between the randomization ratio and the associated factors, including participation rate, type of informed consent, clinical area, and so on. A clearer understanding of RCTs with DUR and its association with factors in trials, for example, participation rate, can optimize trial design and may have important implications for both researchers and users of the medical literature.

Randomized Controlled Trial of Full and Brief Cognitive-Behaviour Therapy and Wait-List for Paediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Bolton, Derek; Williams, Tim; Perrin, Sean; Atkinson, Linda; Gallop, Catherine; Waite, Polly; Salkovskis, Paul

2011-01-01

Background: Reviews and practice guidelines for paediatric obsessive-compulsive disorder (OCD) recommend cognitive-behaviour therapy (CBT) as the psychological treatment of choice, but note that it has not been sufficiently evaluated for children and adolescents and that more randomized controlled trials are needed. The aim of this trial was to…

Methodological Reporting of Randomized Trials in Five Leading Chinese Nursing Journals

PubMed Central

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

2014-01-01

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

Preconception maternal nutrition: a multi-site randomized controlled trial

PubMed Central

2014-01-01

Background Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy. Methods/Study design This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: ≥ 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none. 192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites. Discussion Positive results of this trial will support a paradigm shift in attention to nutrition of all females of

The effectiveness of a web-based brief alcohol intervention in reducing heavy drinking among adolescents aged 15 to 20 years with a low educational background: study protocol for a randomized controlled trial.

PubMed

Voogt, Carmen V; Poelen, Evelien A P; Lemmers, Lex A C J; Engels, Rutger C M E

2012-06-15

The serious negative health consequences of heavy drinking among adolescents is cause for concern, especially among adolescents aged 15 to 20 years with a low educational background. In the Netherlands, there is a lack of alcohol prevention programs directed to the drinking patterns of this specific target group. The study described in this protocol will test the effectiveness of a web-based brief alcohol intervention that aims to reduce alcohol use among heavy drinking adolescents aged 15 to 20 years with a low educational background. The effectiveness of the What Do You Drink (WDYD) web-based brief alcohol intervention will be tested among 750 low-educated, heavy drinking adolescents. It will use a two-arm parallel group cluster randomized controlled trial. Classes of adolescents from educational institutions will be randomly assigned to either the experimental (n = 375: web-based brief alcohol intervention) or control condition (n = 375: no intervention). Primary outcomes measures will be: 1) the percentage of participants who drink within the normative limits of the Dutch National Health Council for low-risk drinking, 2) reductions in mean weekly alcohol consumption, and 3) frequency of binge drinking. The secondary outcome measures include the alcohol-related cognitions, attitudes, self-efficacy, and subjective norms, which will be measured at baseline and at one and six months after the intervention. This study protocol presents the study design of a two-arm parallel-group randomized controlled trial to evaluate the effectiveness of the WDYD web-based brief alcohol intervention. We hypothesized a reduction in mean weekly alcohol consumption and in the frequency of binge drinking in the experimental condition, resulting from the web-based brief alcohol intervention, compared to the control condition. Netherlands Trial Register NTR2971.

From randomized controlled trials to observational studies.

PubMed

Silverman, Stuart L

2009-02-01

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

Financial Management of a Large Multi-site Randomized Clinical Trial

PubMed Central

Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

2014-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

The Prevention Program for Externalizing Problem Behavior (PEP) Improves Child Behavior by Reducing Negative Parenting: Analysis of Mediating Processes in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Hanisch, Charlotte; Hautmann, Christopher; Plück, Julia; Eichelberger, Ilka; Döpfner, Manfred

2014-01-01

Background: Our indicated Prevention program for preschool children with Externalizing Problem behavior (PEP) demonstrated improved parenting and child problem behavior in a randomized controlled efficacy trial and in a study with an effectiveness design. The aim of the present analysis of data from the randomized controlled trial was to identify…

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

PubMed Central

Duncan, Pamela W; Sullivan, Katherine J; Behrman, Andrea L; Azen, Stanley P; Wu, Samuel S; Nadeau, Stephen E; Dobkin, Bruce H; Rose, Dorian K; Tilson, Julie K

2007-01-01

Background Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention. The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions. Methods/Design We will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks. Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment. LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

PubMed

Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

2012-07-01

Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

Lifestyle Modification for Resistant Hypertension: The TRIUMPH Randomized Clinical Trial

PubMed Central

Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Mabe, Stephanie; Watkins, Lana; Lin, Pao-Hwa; Craighead, Linda W.; Babyak, Michael; Tyson, Crystal; Young, Kenlyn; Ashworth, Megan; Kraus, William; Liao, Lawrence; Hinderliter, Alan

2015-01-01

Background Resistant hypertension (RH) is a growing health burden in this country affecting as many as one in five adults being treated for hypertension. RH is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure in this high risk population are a national priority. Methods TRIUMPH is a single site, prospective, randomized clinical trial (RCT) to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie DASH eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (N=150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic blood pressure; secondary endpoints include ambulatory blood pressure and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, blood pressure and CVD risk factors also will be measured at one year follow-up. Conclusions The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on blood presssure and CVD biomarkers in patients with RH after 4 months of treatment, and will determine whether lifestyle changes can be maintained for a year. PMID:26542509

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We

A pilot randomized controlled trial of deprescribing.

PubMed

Beer, Christopher; Loh, Poh-Kooi; Peng, Yan Gee; Potter, Kathleen; Millar, Alasdair

2011-04-01

Polypharmacy and adverse drug reactions are frequent and important among older people. Few clinical trials have evaluated systematic withdrawal of medications among older people. This small, open, study was conducted to determine the feasibility of a randomized controlled deprescribing trial. Ten volunteers living in the community (recruited by media advertising) and 25 volunteers living in residential aged-care facilities (RCFs) were randomized to intervention or control groups. The intervention was gradual withdrawal of one target medication. The primary outcome was the number of intervention participants in whom medication withdrawal could be achieved. Other outcomes measures were quality of life, medication adherence, sleep quality, and cognitive impairment. Participants were aged 80 ± 11 years and were taking 9 ± 2 medications. Fifteen participants commenced medication withdrawal and all ceased or reduced the dose of their target medication. Two subjects withdrew; one was referred for clinical review, and one participant declined further dose reductions. A randomized controlled trial of deprescribing was acceptable to participants. Recruitment in RCFs is feasible. Definitive trials of deprescribing are required.

Clamp-Crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH) - A randomized controlled trial (NCT01049607)

PubMed Central

2011-01-01

Background Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. Methods/Design The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. Discussion The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. Trial Registration ClinicalTrials.gov: NCT01049607 PMID:21888669

"Right from the Start": Randomized Trial Comparing an Attachment Group Intervention to Supportive Home Visiting

ERIC Educational Resources Information Center

Niccols, Alison

2008-01-01

Background: Infant attachment security is a protective factor for future mental health, and may be promoted by individual interventions. Given service demands, it is important to determine if a group-based intervention for parents could be used to enhance infant attachment security. Methods: In a randomized trial involving 76 mothers, an 8-session…

Cancer Screening Knowledge Changes: Results from a Randomized Control Trial of Women with Developmental Disabilities

ERIC Educational Resources Information Center

Parish, Susan L.; Rose, Roderick A.; Luken, Karen; Swaine, Jamie G.; O'Hare, Lindsey

2012-01-01

Background: Women with developmental disabilities are much less likely than nondisabled women to receive cervical and breast cancer screening according to clinical guidelines. One barrier to receipt of screenings is a lack of knowledge about preventive screenings. Method: To address this barrier, we used a randomized control trial (n = 175 women)…

The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

PubMed Central

Seib, Rachael; Prescott, Todd

2005-01-01

Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study)

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP. Methods The trial population was drawn from the Bath and Bristol NHS specialist paediatric CFS or ME service. The study was designed as a pilot randomized trial with children (aged 12 to 18 years) comparing specialist medical care with specialist medical care plus the Lightning Process. Integrated qualitative methodology was used to explore the feasibility and acceptability of the recruitment, randomization and interventions. Results A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012). Recruitment, randomization and both interventions were feasible and acceptable. Participants suggested changes to improve feasibility and acceptability and we incorporated the following in the trial protocol: stopped collecting 6-week outcomes; introduced a second reminder letter; used phone calls to collect primary outcomes from nonresponders; informed participants about different approaches of each intervention and changed our recommendation for the primary outcome for the full study from school attendance to disability (SF-36 physical function subscale) and fatigue (Chalder Fatigue Scale). Conclusions Conducting randomized controlled trials (RCTs) to investigate an alternative treatment such as LP is feasible and acceptable for children with CFS or ME. Feasibility studies that incorporate qualitative methodology enable changes to be made to trial protocols to improve acceptability to participants. This is likely to improve recruitment rate and trial retention. Trial registration Feasibility study first randomization: 29 September 2010. Trial registration: Current Controlled Trials ISRCTN81456207

Assessing the Generalizability of Randomized Trial Results to Target Populations

PubMed Central

Stuart, Elizabeth A.; Bradshaw, Catherine P.; Leaf, Philip J.

2014-01-01

Recent years have seen increasing interest in and attention to evidence-based practices, where the “evidence” generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as “internal validity”), they do not always yield relevant information about the effects in a particular target population (known as “external validity”). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a pre-specified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of School-wide Positive Behavioral Interventions and Supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific

Assessing the generalizability of randomized trial results to target populations.

PubMed

Stuart, Elizabeth A; Bradshaw, Catherine P; Leaf, Philip J

2015-04-01

Recent years have seen increasing interest in and attention to evidence-based practices, where the "evidence" generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as "internal validity"), they do not always yield relevant information about the effects in a particular target population (known as "external validity"). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a prespecified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of school-wide positive behavioral interventions and supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless

Power Calculations for Moderators in Multi-Site Cluster Randomized Trials

ERIC Educational Resources Information Center

Spybrook, Jessaca; Kelcey, Ben; Dong, Nianbo

2016-01-01

Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in evaluation studies of educational programs. A specific type of CRT in which clusters are randomly assigned to treatment within blocks or sites, known as multisite cluster randomized trials (MSCRTs),…

Adaptive Designs for Randomized Trials in Public Health

PubMed Central

Brown, C. Hendricks; Have, Thomas R. Ten; Jo, Booil; Dagne, Getachew; Wyman, Peter A.; Muthén, Bengt; Gibbons, Robert D.

2009-01-01

In this article, we present a discussion of two general ways in which the traditional randomized trial can be modified or adapted in response to the data being collected. We use the term adaptive design to refer to a trial in which characteristics of the study itself, such as the proportion assigned to active intervention versus control, change during the trial in response to data being collected. The term adaptive sequence of trials refers to a decision-making process that fundamentally informs the conceptualization and conduct of each new trial with the results of previous trials. Our discussion below investigates the utility of these two types of adaptations for public health evaluations. Examples are provided to illustrate how adaptation can be used in practice. From these case studies, we discuss whether such evaluations can or should be analyzed as if they were formal randomized trials, and we discuss practical as well as ethical issues arising in the conduct of these new-generation trials. PMID:19296774

The treatment of medial tibial stress syndrome in athletes; a randomized clinical trial

PubMed Central

2012-01-01

Background The only three randomized trials on the treatment of MTSS were all performed in military populations. The treatment options investigated in this study were not previously examined in athletes. This study investigated if functional outcome of three common treatment options for medial tibial stress syndrome (MTSS) in athletes in a non-military setting was the same. Methods The study design was randomized and multi-centered. Physical therapists and sports physicians referred athletes with MTSS to the hospital for inclusion. 81 athletes were assessed for eligibility of which 74 athletes were included and randomized to three treatment groups. Group one performed a graded running program, group two performed a graded running program with additional stretching and strengthening exercises for the calves, while group three performed a graded running program with an additional sports compression stocking. The primary outcome measure was: time to complete a running program (able to run 18 minutes with high intensity) and secondary outcome was: general satisfaction with treatment. Results 74 Athletes were randomized and included of which 14 did not complete the study due a lack of progress (18.9%). The data was analyzed on an intention-to-treat basis. Time to complete a running program and general satisfaction with the treatment were not significantly different between the three treatment groups. Conclusion This was the first randomized trial on the treatment of MTSS in athletes in a non-military setting. No differences were found between the groups for the time to complete a running program. Trial registration CCMO; NL23471.098.08 PMID:22464032

The Design of Cluster Randomized Trials with Random Cross-Classifications

ERIC Educational Resources Information Center

Moerbeek, Mirjam; Safarkhani, Maryam

2018-01-01

Data from cluster randomized trials do not always have a pure hierarchical structure. For instance, students are nested within schools that may be crossed by neighborhoods, and soldiers are nested within army units that may be crossed by mental health-care professionals. It is important that the random cross-classification is taken into account…

A Monte Carlo analysis of breast screening randomized trials.

PubMed

Zamora, Luis I; Forastero, Cristina; Guirado, Damián; Lallena, Antonio M

2016-12-01

To analyze breast screening randomized trials with a Monte Carlo simulation tool. A simulation tool previously developed to simulate breast screening programmes was adapted for that purpose. The history of women participating in the trials was simulated, including a model for survival after local treatment of invasive cancers. Distributions of time gained due to screening detection against symptomatic detection and the overall screening sensitivity were used as inputs. Several randomized controlled trials were simulated. Except for the age range of women involved, all simulations used the same population characteristics and this permitted to analyze their external validity. The relative risks obtained were compared to those quoted for the trials, whose internal validity was addressed by further investigating the reasons of the disagreements observed. The Monte Carlo simulations produce results that are in good agreement with most of the randomized trials analyzed, thus indicating their methodological quality and external validity. A reduction of the breast cancer mortality around 20% appears to be a reasonable value according to the results of the trials that are methodologically correct. Discrepancies observed with Canada I and II trials may be attributed to a low mammography quality and some methodological problems. Kopparberg trial appears to show a low methodological quality. Monte Carlo simulations are a powerful tool to investigate breast screening controlled randomized trials, helping to establish those whose results are reliable enough to be extrapolated to other populations and to design the trial strategies and, eventually, adapting them during their development. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

Does Mass Azithromycin Distribution Impact Child Growth and Nutrition in Niger? A Cluster-Randomized Trial

PubMed Central

Amza, Abdou; Yu, Sun N.; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Zhou, Zhaoxia; West, Sheila K.; Bailey, Robin L.; Gaynor, Bruce D.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.

2014-01-01

Background Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. Methodology In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6–60 months of age. Principal Findings We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). Conclusions/Significance We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association. PMID:25210836

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

PubMed Central

2010-01-01

Background In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain. Method We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Results Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). Conclusions Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance. Trial Registration This study was registered at ClinicalTrials.gov. # NCT00279513 PMID:20380750

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

Intermediate outcomes in randomized clinical trials: an introduction

PubMed Central

2013-01-01

Background Intermediate outcomes are common and typically on the causal pathway to the final outcome. Some examples include noncompliance, missing data, and truncation by death like pregnancy (e.g. when the trial intervention is given to non-pregnant women and the final outcome is preeclampsia, defined only on pregnant women). The intention-to-treat approach does not account properly for them, and more appropriate alternative approaches like principal stratification are not yet widely known. The purposes of this study are to inform researchers that the intention-to-treat approach unfortunately does not fit all problems we face in experimental research, to introduce the principal stratification approach for dealing with intermediate outcomes, and to illustrate its application to a trial of long term calcium supplementation in women at high risk of preeclampsia. Methods Principal stratification and related concepts are introduced. Two ways for estimating causal effects are discussed and their application is illustrated using the calcium trial, where noncompliance and pregnancy are considered as intermediate outcomes, and preeclampsia is the main final outcome. Results The limitations of traditional approaches and methods for dealing with intermediate outcomes are demonstrated. The steps, assumptions and required calculations involved in the application of the principal stratification approach are discussed in detail in the case of our calcium trial. Conclusions The intention-to-treat approach is a very sound one but unfortunately it does not fit all problems we find in randomized clinical trials; this is particularly the case for intermediate outcomes, where alternative approaches like principal stratification should be considered. PMID:23510143

Testing a workplace physical activity intervention: a cluster randomized controlled trial

PubMed Central

2011-01-01

Background Increased physical activity levels benefit both an individuals' health and productivity at work. The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention designed to increase physical activity levels. Methods A total of 1260 participants from 44 UK worksites (based within 5 organizations) were recruited to a cluster randomized controlled trial with worksites randomly allocated to an intervention or control condition. Measurement of physical activity and other variables occurred at baseline, and at 0 months, 3 months and 9 months post-intervention. Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention. The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior, delivered in-house by nominated facilitators. Self-reported physical activity (measured using the IPAQ short-form) and health outcomes were assessed. Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity (from the IPAQ) at any of the follow-up time points controlling for baseline activity. However, the intervention did significantly reduce systolic blood pressure (B = -1.79 mm/Hg) and resting heart rate (B = -2.08 beats) and significantly increased body mass index (B = .18 units) compared to control. The intervention was found not to be cost-effective, however the substantial variability round this estimate suggested that further research is warranted. Conclusions The current study found mixed support for this worksite physical activity intervention. The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale randomized controlled trials in real-world settings. Trial registration Current controlled trials ISRCTN08807396 PMID:21481265

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

CONSORT for Reporting Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration

PubMed Central

Hopewell, Sally; Clarke, Mike; Moher, David; Wager, Elizabeth; Middleton, Philippa; Altman, Douglas G; Schulz, Kenneth F

2008-01-01

Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. Methods and Findings We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. Conclusions CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

PubMed Central

2011-01-01

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011). Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA PMID:21356042

[Methodological quality and reporting quality evaluation of randomized controlled trials published in China Journal of Chinese Materia Medica].

PubMed

Yu, Dan-Dan; Xie, Yan-Ming; Liao, Xing; Zhi, Ying-Jie; Jiang, Jun-Jie; Chen, Wei

2018-02-01

To evaluate the methodological quality and reporting quality of randomized controlled trials(RCTs) published in China Journal of Chinese Materia Medica, we searched CNKI and China Journal of Chinese Materia webpage to collect RCTs since the establishment of the magazine. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of RCTs. The CONSORT 2010 list was adopted as reporting quality evaluating tool. Finally, 184 RCTs were included and evaluated methodologically, of which 97 RCTs were evaluated with reporting quality. For the methodological evaluating, 62 trials(33.70%) reported the random sequence generation; 9(4.89%) trials reported the allocation concealment; 25(13.59%) trials adopted the method of blinding; 30(16.30%) trials reported the number of patients withdrawing, dropping out and those lost to follow-up;2 trials （1.09%） reported trial registration and none of the trial reported the trial protocol; only 8(4.35%) trials reported the sample size estimation in details. For reporting quality appraising, 3 reporting items of 25 items were evaluated with high-quality,including: abstract, participants qualified criteria, and statistical methods; 4 reporting items with medium-quality, including purpose, intervention, random sequence method, and data collection of sites and locations; 9 items with low-quality reporting items including title, backgrounds, random sequence types, allocation concealment, blindness, recruitment of subjects, baseline data, harms, and funding;the rest of items were of extremely low quality(the compliance rate of reporting item<10%). On the whole, the methodological and reporting quality of RCTs published in the magazine are generally low. Further improvement in both methodological and reporting quality for RCTs of traditional Chinese medicine are warranted. It is recommended that the international standards and procedures for RCT design should be strictly followed to conduct high-quality trials

Testing cardiovascular drug safety and efficacy in randomized trials.

PubMed

FitzGerald, Garret A

2014-03-28

Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average but unbiased estimates of efficacy and risk. Concern has been expressed about how unrepresentative populations and conditions that pertain in randomized trials might be of the real world, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials that establish efficacy and those that demonstrate effectiveness, drugs that patients actually consume in the real world for clinical benefit. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of effectiveness with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that average results may conceal considerable interindividual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients. Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria-the individual Numbers Needed to Treat to obtain a benefit, such as a life saved. Here, I will consider some reasons why large phase 3 trials-by far the most expensive element of drug development-may fail to address the unmet medical needs, which should justify such effort and investment.

SMART trial: A randomized clinical trial of self-monitoring in behavioral weight management-design and baseline findings

PubMed Central

Burke, Lora E.; Styn, Mindi A.; Glanz, Karen; Ewing, Linda J.; Elci, Okan U.; Conroy, Margaret B.; Sereika, Susan M.; Acharya, Sushama D.; Music, Edvin; Keating, Alison L.; Sevick, Mary Ann

2009-01-01

Background The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial. Methods The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA + FB). Results We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24 months, retention rate for the first of three cohorts was 90%. Conclusions To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component. PMID:19665588

The C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler, a multi-center randomized controlled trial

PubMed Central

2012-01-01

Background Anastomotic leakage is a major complication in colorectal surgery and with an incidence of 11% the most common cause of morbidity and mortality. In order to reduce the incidence of anastomotic leakage the C-seal is developed. This intraluminal biodegradable drain is stapled to the anastomosis with a circular stapler and prevents extravasation of intracolonic content in case of an anastomotic dehiscence. The aim of this study is to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses, as assessed by anastomotic leakage leading to invasive treatment within 30 days postoperative. Methods The C-seal trial is a prospective multi-center randomized controlled trial with primary endpoint, anastomotic leakage leading to re-intervention within 30 days after operation. In this trial 616 patients will be randomized to the C-seal or control group (1:1), stratified by center, anastomotic height (proximal or distal of peritoneal reflection) and the intention to create a temporary deviating ostomy. Interim analyses are planned after 50% and 75% of patient inclusion. Eligible patients are at least 18 years of age, have any colorectal disease requiring a colorectal anastomosis to be made with a circular stapler in an elective setting, with an ASA-classification < 4. Oral mechanical bowel preparation is mandatory and patients with signs of peritonitis are excluded. The C-seal student team will perform the randomization procedure, supports the operating surgeon during the C-seal application and achieves the monitoring of the trial. Patients are followed for one year after randomization en will be analyzed on an intention to treat basis. Discussion This Randomized Clinical trial is designed to evaluate the effectiveness of the C-seal in preventing clinical anastomotic leakage. Trial registration NTR3080 PMID:23153188

Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in Children

PubMed Central

Pica, Natalie

2016-01-01

BACKGROUND: Trial discontinuation and nonpublication represent potential waste in research resources and lead to compromises in medical evidence. Pediatric trials may be particularly vulnerable to these outcomes given the challenges encountered in conducting trials in children. We aimed to determine the prevalence of discontinuation and nonpublication of randomized clinical trials (RCTs) conducted in pediatric populations. METHODS: Retrospective, cross-sectional study of pediatric RCTs registered in ClinicalTrials.gov from 2008 to 2010. Data were collected from the registry and associated publications identified (final search on September 1, 2015). RESULTS: Of 559 trials, 104 (19%) were discontinued early, accounting for an estimated 8369 pediatric participants. Difficulty with patient accrual (37%) was the most commonly cited reason for discontinuation. Trials were less likely to be discontinued if they were funded by industry compared with academic institutions (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27–0.77). Of the 455 completed trials, 136 (30%) were not published, representing 69 165 pediatric participants. Forty-two unpublished trials posted results on ClinicalTrials.gov. Trials funded by industry were more than twice as likely to result in nonpublication at 24 and 36 months (OR 2.21, 95% CI 1.35–3.64; OR 3.12, 95% CI 1.6–6.08, respectively) and had a longer mean time to publication compared with trials sponsored by academia (33 vs 24 months, P < .001). CONCLUSIONS: In this sample of pediatric RCTs, discontinuation and nonpublication were common, with thousands of children exposed to interventions that did not lead to informative or published findings. Trial funding source was an important determinant of these outcomes, with both academic and industry sponsors contributing to inefficiencies. PMID:27492817

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

Acupuncture for migraine prophylaxis: a randomized controlled trial

PubMed Central

Li, Ying; Zheng, Hui; Witt, Claudia M.; Roll, Stephanie; Yu, Shu-guang; Yan, Jie; Sun, Guo-jie; Zhao, Ling; Huang, Wen-jing; Chang, Xiao-rong; Zhang, Hong-xing; Wang, De-jun; Lan, Lei; Zou, Ran; Liang, Fan-rong

2012-01-01

Background: Acupuncture is commonly used to treat migraine. We assessed the efficacy of acupuncture at migraine-specific acupuncture points compared with other acupuncture points and sham acupuncture. Methods: We performed a multicentre, single-blind randomized controlled trial. In total, 480 patients with migraine were randomly assigned to one of four groups (Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture or sham acupuncture [control]). All groups received 20 treatments, which included electrical stimulation, over a period of four weeks. The primary outcome was the number of days with a migraine experienced during weeks 5–8 after randomization. Our secondary outcomes included the frequency of migraine attack, migraine intensity and migraine-specific quality of life. Results: Compared with patients in the control group, patients in the acupuncture groups reported fewer days with a migraine during weeks 5–8, however the differences between treatments were not significant (p > 0.05). There was a significant reduction in the number of days with a migraine during weeks 13–16 in all acupuncture groups compared with control (Shaoyang-specific acupuncture v. control: difference –1.06 [95% confidence interval (CI) –1.77 to –0.5], p = 0.003; Shaoyang-nonspecific acupuncture v. control: difference –1.22 [95% CI –1.92 to –0.52], p < 0.001; Yangming-specific acupuncture v. control: difference –0.91 [95% CI –1.61 to –0.21], p = 0.011). We found that there was a significant, but not clinically relevant, benefit for almost all secondary outcomes in the three acupuncture groups compared with the control group. We found no relevant differences between the three acupuncture groups. Interpretation: Acupuncture tested appeared to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture. Trial Registration: Clinicaltrials.gov NCT00599586 PMID:22231691

Reporting of participant flow diagrams in published reports of randomized trials.

PubMed

Hopewell, Sally; Hirst, Allison; Collins, Gary S; Mallett, Sue; Yu, Ly-Mee; Altman, Douglas G

2011-12-05

Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial

Dressing wear time after breast reconstruction: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background One of the major risk variables for surgical site infection is wound management. Understanding infection risk factors for breast operations is essential in order to develop infection-prevention strategies and improve surgical outcomes. The aim of this trial is to assess the influence of dressing wear time on surgical site infection rates and skin colonization. Patients’ perception at self-assessment will also be analyzed. Methods/Design This is a two-arm randomized controlled trial. Two hundred breast cancer patients undergoing immediate or delayed breast reconstruction will be prospectively enrolled. Patients will be randomly allocated to group I (dressing removed on postoperative day one) or group II (dressing removed on postoperative day six). Surgical site infections will be defined by standard criteria from the Centers for Disease Control and Prevention (CDC). Skin colonization will be assessed by culture of samples collected at predefined time points. Patients will score dressing wear time with regard to safety, comfort and convenience. Discussion The evidence to support dressing standards for breast surgery wounds is empiric and scarce. CDC recommends protecting, with a sterile dressing for 24 to 48 hours postoperatively, a primarily closed incision, but there is no recommendation to cover this kind of incision beyond 48 hours, or on the appropriate time to shower or bathe with an uncovered incision. The results of the ongoing trial may support standard recommendations regarding dressing wear time after breast reconstruction. Trial registration ClinicalTrials.gov identifier: http://NCT01148823. PMID:23432779

Testing Cardiovascular Drug Safety and Efficacy in Randomized Trials

PubMed Central

FitzGerald, Garret A.

2014-01-01

Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average, but unbiased estimates of efficacy and risk. Concern has been expressed about how “unrepresentative” populations and conditions that pertain in randomized trials might be of the “real world”, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials which establish “efficacy” and those that demonstrate “effectiveness” - drugs that patients actually consume in the “real world” for clinical benefit1. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of “effectiveness” with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that “average” results may conceal considerable inter-individual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients2,3Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria - the individual Numbers Needed to Treat to obtain a benefit, such as a life saved4. Here, I will consider some reasons why large phase 3 trials - by far the most expensive element of drug development - may fail to address the “unmet medical needs” which should justify such effort and investment. PMID:24677235

A randomized trial comparing primary angioplasty versus stent placement for symptomatic intracranial stenosis

PubMed Central

Qureshi, Adnan I; Chaudhry, Saqib A; Siddiq, Farhan; Majidi, Shahram; Rodriguez, Gustavo J; Suri, M Fareed K

2013-01-01

Background: Both primary angioplasty alone and angioplasty with a self-expanding stent have been compared in non-randomized concurrent clinical studies that suggest equivalent results. However, there is no randomized trial that has compared the two procedures in patients with symptomatic high grade intracranial stenosis. Objective: The primary aim of the randomized trial was to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. Methods: The study prospectively evaluated efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥ 50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment. Results: A total of 18 patients were recruited in the study (mean age [±SD] was 64.7 ± 15.1 years); out of these, 12 were men. Of these 18, 10 were treated with primary angioplasty and 8 were treated with angioplasty followed by self-expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The total fluoroscopic time (mean [±SD]) was lower in patients undergoing primary angioplasty 37 [±11] min versus those undergoing angioplasty followed by self-expanding stent 42 [±15] min, P = 0.4321. The stroke and death rate within 1 month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One patient randomized to stent placement continued to have recurrent ischemic symptoms requiring another angioplasty in the vertebral artery on post-procedure Day 2. Conclusions: The trial suggests that a randomized trial comparing primary angioplasty to angioplasty

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

A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial.

PubMed

Morrison, Deborah; Wyke, Sally; Thomson, Neil C; McConnachie, Alex; Agur, Karolina; Saunderson, Kathryn; Chaudhuri, Rekha; Mair, Frances S

2014-05-24

The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes. The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status). Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of

Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

PubMed

Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

2016-02-10

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving

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.

Bayesian statistical inference enhances the interpretation of contemporary randomized controlled trials.

PubMed

Wijeysundera, Duminda N; Austin, Peter C; Hux, Janet E; Beattie, W Scott; Laupacis, Andreas

2009-01-01

Randomized trials generally use "frequentist" statistics based on P-values and 95% confidence intervals. Frequentist methods have limitations that might be overcome, in part, by Bayesian inference. To illustrate these advantages, we re-analyzed randomized trials published in four general medical journals during 2004. We used Medline to identify randomized superiority trials with two parallel arms, individual-level randomization and dichotomous or time-to-event primary outcomes. Studies with P<0.05 in favor of the intervention were deemed "positive"; otherwise, they were "negative." We used several prior distributions and exact conjugate analyses to calculate Bayesian posterior probabilities for clinically relevant effects. Of 88 included studies, 39 were positive using a frequentist analysis. Although the Bayesian posterior probabilities of any benefit (relative risk or hazard ratio<1) were high in positive studies, these probabilities were lower and variable for larger benefits. The positive studies had only moderate probabilities for exceeding the effects that were assumed for calculating the sample size. By comparison, there were moderate probabilities of any benefit in negative studies. Bayesian and frequentist analyses complement each other when interpreting the results of randomized trials. Future reports of randomized trials should include both.

Randomized controlled pilot trial of naloxone‐on‐release to prevent post‐prison opioid overdose deaths

PubMed Central

Parmar, Mahesh K. B.; Strang, John; Choo, Louise; Meade, Angela M.

2016-01-01

Abstract Background and Aims Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin injection have a high risk of drug‐related death soon after release from prison. The NALoxone InVEstigation (N‐ALIVE) pilot trial (ISRCTN34044390) tested feasibility measures for randomized provision of naloxone‐on‐release (NOR) to eligible prisoners in England. Design. Parallel‐group randomized controlled pilot trial. Setting English prisons. Participants A total of 1685 adult heroin injectors, incarcerated for at least 7 days pre‐randomization, release due within 3 months and more than 6 months since previous N‐ALIVE release. Intervention Using 1 : 1 minimization, prisoners were randomized to receive on release a pack containing either a single ‘rescue’ injection of naloxone or a control pack with no syringe. Measurements Key feasibility outcomes were tested against prior expectations: on participation (14 English prisons; 2800 prisoners), consent (75% for randomization), returned prisoner self‐questionnaires (RPSQs: 207), NOR‐carriage (75% in first 4 weeks) and overdose presence (80%). Findings Prisons (16) and prisoners (1685) were willing to participate [consent rate, 95% confidence interval (CI) = 70–74%]; 218 RPSQs were received; NOR‐carriage (95% CI = 63–79%) and overdose presence (95% CI = 75–84%) were as expected. We randomized 842 to NOR and 843 to control during 30 months but stopped early, because only one‐third of NOR administrations were to the ex‐prisoner. Nine deaths within 12 weeks of release were registered for 1557 randomized participants released before 9 December 2014. Conclusions Large randomized trials are feasible with prison populations. Provision of take‐home emergency naloxone prior to prison release may be a life‐saving interim measure to prevent heroin overdose deaths among ex‐prisoners and the wider population. PMID:27776382

Focus on Function – a randomized controlled trial comparing two rehabilitation interventions for young children with cerebral palsy

PubMed Central

Law, Mary; Darrah, Johanna; Pollock, Nancy; Rosenbaum, Peter; Russell, Dianne; Walter, Stephen D; Petrenchik, Theresa; Wilson, Brenda; Wright, Virginia

2007-01-01

Background Children with cerebral palsy receive a variety of long-term physical and occupational therapy interventions to facilitate development and to enhance functional independence in movement, self-care, play, school activities and leisure. Considerable human and financial resources are directed at the "intervention" of the problems of cerebral palsy, although the available evidence supporting current interventions is inconclusive. A considerable degree of uncertainty remains about the appropriate therapeutic approaches to manage the habilitation of children with cerebral palsy. The primary objective of this project is to conduct a multi-site randomized clinical trial to evaluate the efficacy of a task/context-focused approach compared to a child-focused remediation approach in improving performance of functional tasks and mobility, increasing participation in everyday activities, and improving quality of life in children 12 months to 5 years of age who have cerebral palsy. Method/Design A multi-centred randomized controlled trial research design will be used. Children will be recruited from a representative sample of children attending publicly-funded regional children's rehabilitation centers serving children with disabilities in Ontario and Alberta in Canada. Target sample size is 220 children with cerebral palsy aged 12 months to 5 years at recruitment date. Therapists are randomly assigned to deliver either a context-focused approach or a child-focused approach. Children follow their therapist into their treatment arm. Outcomes will be evaluated at baseline, after 6 months of treatment and at a 3-month follow-up period. Outcomes represent the components of the International Classification of Functioning, Disability and Health, including body function and structure (range of motion), activities (performance of functional tasks, motor function), participation (involvement in formal and informal activities), and environment (parent perceptions of care

A Randomized Controlled Trial of Professional Development for Interdisciplinary Civic Education: Impacts on Humanities Teachers and Their Students

ERIC Educational Resources Information Center

Barr, Dennis J.; Boulay, Beth; Selman, Robert L.; McCormick, Rachel; Lowenstein, Ethan; Gamse, Beth; Fine, Melinda; Leonard, M. Brielle

2015-01-01

Background/Context: Billions of dollars are spent annually on professional development (PD) for educators, yet few randomized controlled trials (RCT) have demonstrated the ultimate impact PD has on student learning. Further, while policymakers and others speak to the role schools should play in developing students' civic awareness, RCTs of PD…

LMA Supreme for neonatal resuscitation: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background The most important action in the resuscitation of a newborn in the delivery room is to establish effective assisted ventilation. The face mask and endotracheal tube are the devices used to achieve this goal. Laryngeal mask airways that fit over the laryngeal inlet have been shown to be effective for ventilating newborns at birth and should be considered as an alternative to facemask ventilation or endotracheal intubation among newborns weighing >2,000 g or delivered ≥34 weeks’ gestation. A recent systematic review and meta-analysis of supraglottic airways in neonatal resuscitation reported the results of four randomized controlled trials (RCTs) stating that fewer infants in the group using laryngeal mask airways required endotracheal intubation (1.5%) compared to the group using face masks (12.0%). However, there were methodological concerns over all the RCTs including the fact that the majority of the operators in the trials were anesthesiologists. Our hypothesis is based on the assumption that ventilating newborns needing positive pressure ventilation with a laryngeal mask airway will be more effective than ventilating with a face mask in a setting where neonatal resuscitation is performed by midwives, nurses, and pediatricians. The primary aim of this study will be to assess the effectiveness of the laryngeal mask airway over the face mask in preventing the need for endotracheal intubation. Methods/design This will be an open, prospective, randomized, single center, clinical trial. In this study, 142 newborns weighing >1,500 g or delivered ≥34 weeks gestation needing positive pressure ventilation at birth will be randomized to be ventilated with a laryngeal mask airway (LMA SupremeTM, LMA Company, UK - intervention group) or with a face mask (control group). Primary outcome: Proportion of newborns needing endotracheal intubation. Secondary outcomes: Apgar score at 5 minutes, time to first breath, onset of the first cry, duration of

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

Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.

PubMed

Bhandari, Mohit; Tornetta, Paul; Ellis, Thomas; Audige, Laurent; Sprague, Sheila; Kuo, Jonathann C; Swiontkowski, Marc F

2004-01-01

There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. We conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs. We identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

PubMed Central

Damiani, Lucas Petri; Berwanger, Otavio; Paisani, Denise; Laranjeira, Ligia Nasi; Suzumura, Erica Aranha; Amato, Marcelo Britto Passos; Carvalho, Carlos Roberto Ribeiro; Cavalcanti, Alexandre Biasi

2017-01-01

Background The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). Objective To describe the data management process and statistical analysis plan. Methods The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. Conclusion According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. Trial registration ClinicalTrials.gov number, NCT01374022. PMID:28977255

Lack of Interaction between Sensing-Intuitive Learning Styles and Problem-First versus Information-First Instruction: A Randomized Crossover Trial

ERIC Educational Resources Information Center

Cook, David A.; Thompson, Warren G.; Thomas, Kris G.; Thomas, Matthew R.

2009-01-01

Background: Adaptation to learning styles has been proposed to enhance learning. Objective: We hypothesized that learners with sensing learning style would perform better using a problem-first instructional method while intuitive learners would do better using an information-first method. Design: Randomized, controlled, crossover trial. Setting:…

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Acupuncture as prophylaxis for menstrual-related migraine: study protocol for a multicenter randomized controlled trial

PubMed Central

2013-01-01

Background Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. Trial registration ISRCTN: ISRCTN57133712 PMID:24195839

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

Robotic-assisted versus laparoscopic colorectal surgery: a meta-analysis of four randomized controlled trials

PubMed Central

2014-01-01

Background Robotic-assisted laparoscopy is popularly performed for colorectal disease. The objective of this meta-analysis was to compare the safety and efficacy of robotic-assisted colorectal surgery (RCS) and laparoscopic colorectal surgery (LCS) for colorectal disease based on randomized controlled trial studies. Methods Literature searches of electronic databases (Pubmed, Web of Science, and Cochrane Library) were performed to identify randomized controlled trial studies that compared the clinical or oncologic outcomes of RCS and LCS. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were mean differences and odds ratios for continuous and dichotomous variables, respectively. Fixed-effects or random-effects models were adopted according to heterogeneity. Results Four randomized controlled trial studies were identified for this meta-analysis. In total, 110 patients underwent RCS, and 116 patients underwent LCS. The results revealed that estimated blood losses (EBLs), conversion rates and times to the recovery of bowel function were significantly reduced following RCS compared with LCS. There were no significant differences in complication rates, lengths of hospital stays, proximal margins, distal margins or harvested lymph nodes between the two techniques. Conclusions RCS is a promising technique and is a safe and effective alternative to LCS for colorectal surgery. The advantages of RCS include reduced EBLs, lower conversion rates and shorter times to the recovery of bowel function. Further studies are required to define the financial effects of RCS and the effects of RCS on long-term oncologic outcomes. PMID:24767102

A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)

PubMed Central

2010-01-01

Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302 PMID:20334685

A Mixed-Methods Randomized Controlled Trial of Financial Incentives and Peer Networks to Promote Walking among Older Adults

ERIC Educational Resources Information Center

Kullgren, Jeffrey T.; Harkins, Kristin A.; Bellamy, Scarlett L.; Gonzales, Amy; Tao, Yuanyuan; Zhu, Jingsan; Volpp, Kevin G.; Asch, David A.; Heisler, Michele; Karlawish, Jason

2014-01-01

Background: Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more. Methods: We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants…

Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review.

PubMed

Taljaard, Monica; Hemming, Karla; Shah, Lena; Giraudeau, Bruno; Grimshaw, Jeremy M; Weijer, Charles

2017-08-01

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants-yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or

Cluster Randomized-Controlled Trial of Interventions to Improve Health for Adults with Intellectual Disability Who Live in Private Dwellings

ERIC Educational Resources Information Center

Lennox, Nicholas; Bain, Chris; Rey-Conde, Therese; Taylor, Miriam; Boyle, Frances M.; Purdie, David M.; Ware, Robert S.

2010-01-01

Background: People with intellectual disability who live in the community often have poor health and healthcare, partly as a consequence of poor communication, recall difficulties and incomplete patient health information. Materials and Methods: A cluster randomized-controlled trial with 2 x 2 factorial design was conducted with adults with…

Movement-Pattern Training to Improve Function in People With Chronic Hip Joint Pain: A Feasibility Randomized Clinical Trial.

PubMed

Harris-Hayes, Marcie; Czuppon, Sylvia; Van Dillen, Linda R; Steger-May, Karen; Sahrmann, Shirley; Schootman, Mario; Salsich, Gretchen B; Clohisy, John C; Mueller, Michael J

2016-06-01

Study Design Feasibility randomized clinical trial. Background Rehabilitation may be an appropriate treatment strategy for patients with chronic hip joint pain; however, the evidence related to the effectiveness of rehabilitation is limited. Objectives To assess feasibility of performing a randomized clinical trial to investigate the effectiveness of movement-pattern training (MPT) to improve function in people with chronic hip joint pain. Methods Thirty-five patients with chronic hip joint pain were randomized into a treatment (MPT) group or a control (wait-list) group. The MPT program included 6 one-hour supervised sessions and incorporated (1) task-specific training for basic functional tasks and symptom-provoking tasks, and (2) strengthening of hip musculature. The wait-list group received no treatment. Primary outcomes for feasibility were patient retention and adherence. Secondary outcomes to assess treatment effects were patient-reported function (Hip disability and Osteoarthritis Outcome Score), lower extremity kinematics, and hip muscle strength. Results Retention rates did not differ between the MPT (89%) and wait-list groups (94%, P = 1.0). Sixteen of the 18 patients (89%) in the MPT group attended at least 80% of the treatment sessions. For the home exercise program, 89% of patients reported performing their home program at least once per day. Secondary outcomes support the rationale for conduct of a superiority randomized clinical trial. Conclusion Based on retention and adherence rates, a larger randomized clinical trial appears feasible and warranted to assess treatment effects more precisely. Data from this feasibility study will inform our future clinical trial. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2016;46(6):452-461. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6279.

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

PubMed Central

2011-01-01

Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in

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

PubMed

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

2016-12-15

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

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

PubMed Central

2012-01-01

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

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

Preventing Depression in Final Year Secondary Students: School-Based Randomized Controlled Trial

PubMed Central

Perry, Yael; Werner-Seidler, Aliza; Calear, Alison; Mackinnon, Andrew; King, Catherine; Scott, Jan; Merry, Sally; Fleming, Theresa; Stasiak, Karolina; Batterham, Philip J

2017-01-01

Background Depression often emerges for the first time during adolescence. There is accumulating evidence that universal depression prevention programs may have the capacity to reduce the impact of depression when delivered in the school environment. Objective This trial investigated the effectiveness of SPARX-R, a gamified online cognitive behavior therapy intervention for the prevention of depression relative to an attention-matched control intervention delivered to students prior to facing a significant stressor—final secondary school exams. It was hypothesized that delivering a prevention intervention in advance of a stressor would reduce depressive symptoms relative to the control group. Methods A cluster randomized controlled trial was conducted in 10 government schools in Sydney, Australia. Participants were 540 final year secondary students (mean 16.7 [SD 0.51] years), and clusters at the school level were randomly allocated to SPARX-R or the control intervention. Interventions were delivered weekly in 7 modules, each taking approximately 20 to 30 minutes to complete. The primary outcome was symptoms of depression as measured by the Major Depression Inventory. Intention-to-treat analyses were performed. Results Compared to controls, participants in the SPARX-R condition (n=242) showed significantly reduced depression symptoms relative to the control (n=298) at post-intervention (Cohen d=0.29) and 6 months post-baseline (d=0.21) but not at 18 months post-baseline (d=0.33). Conclusions This is the first trial to demonstrate a preventive effect on depressive symptoms prior to a significant and universal stressor in adolescents. It demonstrates that an online intervention delivered in advance of a stressful experience can reduce the impact of such an event on the potential development or exacerbation of depression. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000316606; https://www.anzctr.org.au/Trial/Registration/Trial

COACH trial: A randomized controlled trial of nurse practitioner/community health worker cardiovascular disease risk reduction in urban community health centers: Rationale and design

PubMed Central

Allen, Jerilyn K; Himmelfarb, Cheryl R Dennison; Szanton, Sarah L; Bone, Lee; Hill, Martha N; Levine, David M

2011-01-01

Background Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, implementation of risk-reducing practices remains poor. This paper describes the rationale and design of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of CVD risk reduction delivered by nurse practitioner (NP)/community health worker (CHW) teams versus enhanced usual care in improving the proportion of patients in urban community health centers who achieve goal levels recommended by national guidelines for lipids, blood pressure, HbA1c and prescription of appropriate medications. Methods The COACH (Community Outreach and Cardiovascular Health) trial is a randomized controlled trial in which patients at federally-qualified community health centers were randomly assigned to one of two groups: comprehensive intensive management of CVD risk factors for one year by a NP/CHW team or an enhanced usual care control group. Results A total of 3899 patients were assessed for eligibility and 525 were randomized. Groups were comparable at baseline on sociodemographic and clinical characteristics with the exception of statistically significant differences in total cholesterol and hemoglobin A1c. Conclusions This study is a novel amalgam of multilevel interdisciplinary strategies to translate highly efficacious therapies to low-income federally-funded health centers that care for patients who carry a disproportionate burden of CVD, type 2 diabetes and uncontrolled CVD risk factors. The impact of such a community clinic-based intervention is potentially enormous. PMID:21241828

Review of Recent Methodological Developments in Group-Randomized Trials: Part 1-Design.

PubMed

Turner, Elizabeth L; Li, Fan; Gallis, John A; Prague, Melanie; Murray, David M

2017-06-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis.

Evaluating the Flipped Classroom: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Wozny, Nathan; Balser, Cary; Ives, Drew

2018-01-01

Despite recent interest in flipped classrooms, rigorous research evaluating their effectiveness is sparse. In this study, the authors implement a randomized controlled trial to evaluate the effect of a flipped classroom technique relative to a traditional lecture in an introductory undergraduate econometrics course. Random assignment enables the…

An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial

PubMed Central

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J. Mark G.

2014-01-01

Background Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised. Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. Methods We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources. Results Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other

A Framework for Designing Cluster Randomized Trials with Binary Outcomes

ERIC Educational Resources Information Center

Spybrook, Jessaca; Martinez, Andres

2011-01-01

The purpose of this paper is to provide a frame work for approaching a power analysis for a CRT (cluster randomized trial) with a binary outcome. The authors suggest a framework in the context of a simple CRT and then extend it to a blocked design, or a multi-site cluster randomized trial (MSCRT). The framework is based on proportions, an…

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET)

PubMed Central

2013-01-01

Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as against returning incidental genetic findings in clinical trials. For instance, reporting incidental findings in clinical trials may improve the investigator-participant relationship and the satisfaction of participation, but it may also blur the line between clinical care and research. The issues of whether and how to return incidental genetic findings, including the costs of doing so, should be considered when developing clinical trial protocols. Once decided, plans related to sharing individual results from the aim(s) of the trial, as well as incidental findings, should be discussed explicitly in the consent form. Institutional Review Boards (IRBs) and other study-specific governing bodies should be part of the decision as to if, when, and how to return incidental findings, including when plans in this regard are being reconsidered. PMID:23363732

Marketing depression care management to employers: design of a randomized controlled trial

PubMed Central

2010-01-01

Background Randomized trials demonstrate that depression care management can improve clinical and work outcomes sufficiently for selected employers to realize a return on investment. Employers can now purchase depression products that provide depression care management, defined as employee screening, education, monitoring, and clinician feedback for all depressed employees. We developed an intervention to encourage employers to purchase a depression product that offers the type, intensity, and duration of care management shown to improve clinical and work outcomes. Methods In a randomized controlled trial conducted with 360 employers of 30 regional business coalitions, the research team proposes to compare the impact of a value-based marketing intervention to usual-care marketing on employer purchase of depression products. The study will also identify mediators and organizational-level moderators of intervention impact. Employers randomized to the value-based condition receive a presentation encouraging them to purchase depression products scientifically shown to benefit the employee and the employer. Employers randomized to the usual-care condition receive a presentation encouraging them to monitor and improve quality indicators for outpatient depression treatment. Because previous research demonstrates that the usual-care intervention will have little to no impact on employer purchasing, depression product purchasing rates in the usual-care condition capture vendor efforts to market depression products to employers in both conditions while the value-based intervention is being conducted. Employers in both conditions are also provided free technical assistance to undertake the actions each presentation encourages. The research team will use intent-to-treat models of all available data to evaluate intervention impact on the purchase of depression products using a cumulative incidence analysis of 12- and 24-month data. Discussion By addressing the 'value to whom

Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials123

PubMed Central

Juraschek, Stephen P; Guallar, Eliseo; Appel, Lawrence J

2012-01-01

Background: In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure–lowering effects of vitamin C in clinical trials is inconsistent. Objective: The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP. Design: We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance. Results: Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were −3.84 mm Hg (95% CI: −5.29, −2.38 mm Hg; P < 0.01) and −1.48 mm Hg (95% CI: −2.86, −0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were −4.85 mm Hg (P < 0.01) and −1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. Conclusions: In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed. PMID:22492364

Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial

PubMed Central

Stephenson, Mary D.; Kutteh, William H.; Purkiss, Susan; Librach, Cliff; Schultz, Patricia; Houlihan, Edwina; Liao, Chuanhong

2010-01-01

BACKGROUND Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed. METHODS We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14–21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18–20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation. RESULTS A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41–4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06–18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59–3.48). CONCLUSIONS This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study

PRagmatic trial Of Video Education in Nursing homes: The design and rationale for a pragmatic cluster randomized trial in the nursing home setting.

PubMed

Mor, Vincent; Volandes, Angelo E; Gutman, Roee; Gatsonis, Constantine; Mitchell, Susan L

2017-04-01

Background/Aims Nursing homes are complex healthcare systems serving an increasingly sick population. Nursing homes must engage patients in advance care planning, but do so inconsistently. Video decision support tools improved advance care planning in small randomized controlled trials. Pragmatic trials are increasingly employed in health services research, although not commonly in the nursing home setting to which they are well-suited. This report presents the design and rationale for a pragmatic cluster randomized controlled trial that evaluated the "real world" application of an Advance Care Planning Video Program in two large US nursing home healthcare systems. Methods PRagmatic trial Of Video Education in Nursing homes was conducted in 360 nursing homes (N = 119 intervention/N = 241 control) owned by two healthcare systems. Over an 18-month implementation period, intervention facilities were instructed to offer the Advance Care Planning Video Program to all patients. Control facilities employed usual advance care planning practices. Patient characteristics and outcomes were ascertained from Medicare Claims, Minimum Data Set assessments, and facility electronic medical record data. Intervention adherence was measured using a Video Status Report embedded into electronic medical record systems. The primary outcome was the number of hospitalizations/person-day alive among long-stay patients with advanced dementia or cardiopulmonary disease. The rationale for the approaches to facility randomization and recruitment, intervention implementation, population selection, data acquisition, regulatory issues, and statistical analyses are discussed. Results The large number of well-characterized candidate facilities enabled several unique design features including stratification on historical hospitalization rates, randomization prior to recruitment, and 2:1 control to intervention facilities ratio. Strong endorsement from corporate leadership made randomization

Summer School Effects in a Randomized Field Trial

ERIC Educational Resources Information Center

Zvoch, Keith; Stevens, Joseph J.

2013-01-01

This field-based randomized trial examined the effect of assignment to and participation in summer school for two moderately at-risk samples of struggling readers. Application of multiple regression models to difference scores capturing the change in summer reading fluency revealed that kindergarten students randomly assigned to summer school…

Design and methods for a randomized clinical trial treating comorbid obesity and major depressive disorder

PubMed Central

Schneider, Kristin L; Bodenlos, Jamie S; Ma, Yunsheng; Olendzki, Barbara; Oleski, Jessica; Merriam, Philip; Crawford, Sybil; Ockene, Ira S; Pagoto, Sherry L

2008-01-01

Background Obesity is often comorbid with depression and individuals with this comorbidity fare worse in behavioral weight loss treatment. Treating depression directly prior to behavioral weight loss treatment might bolster weight loss outcomes in this population, but this has not yet been tested in a randomized clinical trial. Methods and design This randomized clinical trial will examine whether behavior therapy for depression administered prior to standard weight loss treatment produces greater weight loss than standard weight loss treatment alone. Obese women with major depressive disorder (N = 174) will be recruited from primary care clinics and the community and randomly assigned to one of the two treatment conditions. Treatment will last 2 years, and will include a 6-month intensive treatment phase followed by an 18-month maintenance phase. Follow-up assessment will occur at 6-months and 1- and 2 years following randomization. The primary outcome is weight loss. The study was designed to provide 90% power for detecting a weight change difference between conditions of 3.1 kg (standard deviation of 5.5 kg) at 1-year assuming a 25% rate of loss to follow-up. Secondary outcomes include depression, physical activity, dietary intake, psychosocial variables and cardiovascular risk factors. Potential mediators (e.g., adherence, depression, physical activity and caloric intake) of the intervention effect on weight change will also be examined. Discussion Treating depression before administering intensive health behavior interventions could potentially boost the impact on both mental and physical health outcomes. Trial registration NCT00572520 PMID:18793398

Review of Recent Methodological Developments in Group-Randomized Trials: Part 2-Analysis.

PubMed

Turner, Elizabeth L; Prague, Melanie; Gallis, John A; Li, Fan; Murray, David M

2017-07-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have updated that review with developments in analysis of the past 13 years, with a companion article to focus on developments in design. We discuss developments in the topics of the earlier review (e.g., methods for parallel-arm GRTs, individually randomized group-treatment trials, and missing data) and in new topics, including methods to account for multiple-level clustering and alternative estimation methods (e.g., augmented generalized estimating equations, targeted maximum likelihood, and quadratic inference functions). In addition, we describe developments in analysis of alternative group designs (including stepped-wedge GRTs, network-randomized trials, and pseudocluster randomized trials), which require clustering to be accounted for in their design and analysis.

[Antepartum perineal massage: review of randomized trials].

PubMed

Vendittelli, F; Tabaste, J L; Janky, E

2001-10-01

To assess the effectiveness of ante partum perineal massage to reduce the number of perineal injuries and episiotomies through a survey of the existing literature. [corrected] A search both in English and French on randomized clinical trials using the Medline and Cochrane Library databases. The key words: "Perineum", "massage", "perineum injuries", "randomized controlled trial" were selected from the years 1966 to November 2000. Four randomized controlled trials were found. The definition of the selected issues, as well as the included and excluded criteria varied according to the authors. Perineal massages seemed to reduce the occurrence of perineal injuries and episiotomies, mostly among primipara: Labrecque et al. in 1999, noted an OR of 0.56; 95% CI: 0.61-1.31 and at the opposite an increased rate of intact perineum in the massage group (OR = 1.79; 95% CI 1.27-2.52]; and Shipman et al. in 1997 stressed among women of > or = 30 years old an augmentation of intact perineum in the intervention group (OR = 1.93; 95% CI 1.08-3.48), and in the logistic regression taking into account age and birth weight they found a reduction of episiotomies and important perineal injuries (p = 0.02). Ante partum perineal massages would seem valid but further studies would be necessary to evaluate the utility of this intervention in the avoidance of serious perineal injuries and the women's satisfaction.

Internet treatment for social anxiety disorder in Romania: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania. Methods Participants with social anxiety disorder (N = 96) will be recruited via newspapers, online banners and Facebook. Participants will be randomized to either: a) an active treatment, or b) a waiting list control group. The treatment will have a guided iCBT format and will last for nine weeks. Self-report questionnaires on social phobia, anxiety, depression, treatment credibility and irrational thinking will be used. All assessments will be collected pre, post and at follow-up (six months after intervention). Liebowitz Social Anxiety Scale – Self-Report version (LSAS-SR) will be the primary outcome measure and will be administrated on a weekly basis in both conditions. Discussion The present randomized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested. This trial will add to the body of knowledge on the efficacy of iCBT, and the results might lead to an increase of the accessibility of evidence-based psychological treatment in Romania. Trial registration ClinicalTrials.gov: NCT01557894 PMID:23111108

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

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

PubMed Central

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

2007-01-01

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

Cognitive Function in a Randomized Trial of Evolocumab.

PubMed

Giugliano, Robert P; Mach, François; Zavitz, Kenton; Kurtz, Christopher; Im, Kyungah; Kanevsky, Estella; Schneider, Jingjing; Wang, Huei; Keech, Anthony; Pedersen, Terje R; Sabatine, Marc S; Sever, Peter S; Robinson, Jennifer G; Honarpour, Narimon; Wasserman, Scott M; Ott, Brian R

2017-08-17

Background Findings from clinical trials of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. Methods In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the

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…

Enhancing access to reports of randomized trials published world-wide – the contribution of EMBASE records to the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library

PubMed Central

Lefebvre, Carol; Eisinga, Anne; McDonald, Steve; Paul, Nina

2008-01-01

Background Randomized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic reviews of effectiveness. Searching for reports of randomized trials in databases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter. Objectives The objectives of this study are to devise a search strategy for identifying reports of randomized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, with the permission of Elsevier, the publishers of EMBASE. Methods A highly sensitive search strategy was designed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles, abstracts, EMTREE terms (or some combination of these) of reports of trials indexed in EMBASE. This search strategy was run against EMBASE from 1980 to 2005 (1974 to 2005 for four of the terms) and records retrieved by the search, which were not already indexed as randomized trials in MEDLINE, were downloaded from EMBASE, printed and read. An analysis of the language of publication was conducted for the reports of trials published in 2005 (the most recent year completed at the time of this study). Results Twenty-two search terms were used (including nine which were later rejected due to poor cumulative precision). More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as randomized trials in MEDLINE. These are now easily identifiable in CENTRAL, in The Cochrane Library. Cumulative sensitivity ranged from 0.1% to 60% and cumulative precision ranged from 8% to 61%. The truncated term 'random$' identified 60% of the total number of reports of trials but only 35% of the more than 130

Electronic prompts significantly increase response rates to postal questionnaires: a randomized trial within a randomized trial and meta-analysis.

PubMed

Clark, Laura; Ronaldson, Sarah; Dyson, Lisa; Hewitt, Catherine; Torgerson, David; Adamson, Joy

2015-12-01

To assess the effectiveness of sending electronic prompts to randomized controlled trial participants to return study questionnaires. A "trial within a trial" embedded within a study determining the effectiveness of chronic obstructive pulmonary disease (DOC) screening on smoking cessation. Those participants taking part in DOC who provided a mobile phone number and/or an electronic mail address were randomized to either receive an electronic prompt or no electronic prompt to return a study questionnaire. The results were combined with two previous studies in a meta-analysis. A total of 437 participants were randomized: 226 to the electronic prompt group and 211 to the control group. A total of 285 (65.2%) participants returned the follow-up questionnaire: 157 (69.5%) in the electronic prompt group and 128 (60.7%) in the control group [difference 8.8%; 95% confidence interval (CI): -0.11%, 17.7%; P = 0.05]. The mean time to response was 23 days in the electronic prompt group and 33 days in the control group (hazard ratio = 1.27; 95% CI: 1.105, 1.47). The meta-analysis of all three studies showed an increase in response rate of 7.1% (95% CI: 0.8%, 13.3%). The use of electronic prompts increased response rates and reduces the time to response. Copyright © 2015 Elsevier Inc. All rights reserved.

The relaxation exercise and social support trial-resst: study protocol for a randomized community based trial

PubMed Central

2011-01-01

Background Studies suggests a possible link between vaginal discharge and common mental distress, as well as highlight the implications of the subjective burden of disease and its link with mental health. Methods/Design This is a community-based intervention trial that aims to evaluate the impact of a psycho-social intervention on medically unexplained vaginal discharge (MUVD) in a group of married, low-income Lebanese women, aged 18-49, and suffering from low to moderate levels of anxiety and/or depression. The intervention consisted of 12 sessions of structured social support, problem solving techniques, group discussions and trainer-supervised relaxation exercises (twice per week over six weeks). Women were recruited from Hey el Selloum, a southern disadvantaged suburb of Beirut, Lebanon, during an open recruitment campaign. The primary outcome was self-reported MUVD, upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Intent to treat analysis will be used. Discussion The results will indicate whether the proposed psychosocial intervention was effective in reducing MUVD (possibly mediated by common mental distress). Trial Registration The trial is registered at the Wellcome Trust Registry, ISRCTN assigned: ISRCTN: ISRCTN98441241 PMID:21864414

Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

PubMed

Free, Caroline; Hoile, Elizabeth; Robertson, Steven; Knight, Rosemary

2010-06-01

Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. Single blind controlled trials with allocation concealment. Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial

DTIC Science & Technology

2016-03-01

AWARD NUMBER: W81XWH-11-2-0123 TITLE: Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial PRINCIPAL INVESTIGATOR: Dr...Caring Letters for Military Suicide Prevention: A Randomized 5a. CONTRACT NUMBER Controlled Trial 5b. GRANT NUMBER W81XWH-11-2-0123 5c. PROGRAM...determine if the intervention is effective in preventing suicide and suicidal behaviors among Service Members and Veterans. The “caring letters

Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial

DTIC Science & Technology

2017-03-01

AWARD NUMBER: W81XWH-11-2-0123 TITLE: Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial PRINCIPAL INVESTIGATOR: Dr...Caring Letters for Military Suicide Prevention: A Randomized 5a. CONTRACT NUMBER Controlled Trial 5b. GRANT NUMBER W81XWH-11-2-0123 5c. PROGRAM...determine if the intervention is effective in preventing suicide and suicidal behaviors among Service Members and Veterans. The “caring letters” concept

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Rosenblat, Joshua D; Kakar, Ron

2016-01-01

Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

PubMed

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of beta-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of beta-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

PubMed Central

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction. PMID:11806769

A randomized trial of enhanced HIV risk reduction and vaccine trial education interventions among HIV-negative, high-risk women who use non-injection drugs: The UNITY Study

PubMed Central

Koblin, Beryl A.; Bonner, Sebastian; Hoover, Donald R.; Xu, Guozhen; Lucy, Debbie; Fortin, Princess; Putnam, Sara; Latka, Mary H.

2014-01-01

Background Limited data are available on interventions to reduce sexual risk behaviors and increase knowledge of HIV vaccine trial concepts in high risk populations eligible to participate in HIV vaccine efficacy trials. Methods The UNITY Study was a two-arm randomized trial to determine the efficacy of enhanced HIV risk reduction and vaccine trial education interventions to reduce the occurrence of unprotected vaginal sex acts and increase HIV vaccine trial knowledge among 311 HIV-negative non-injection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk reduction counseling consisting of three one-on-one counseling sessions were compared to standard conditions. Follow-up visits at one week and one, six and twelve months after randomization included HIV testing and assessment of outcomes. Results During follow up, the percent of women reporting sexual risk behaviors declined significantly, but did not differ significantly by study arm. Knowledge of HIV vaccine trial concepts significantly increased but did not significantly differ by study arm. Concepts about HIV vaccine trials not adequately addressed by either condition included those related to testing a vaccine for both efficacy and safety, guarantees about participation in future vaccine trials, assurances of safety, medical care, and assumptions about any protective effect of a test vaccine. Conclusions Further research is needed to boost educational efforts and strengthen risk reduction counseling among high-risk non-injection drug using women. PMID:20190585

Physical activity as an aid to smoking cessation during pregnancy (LEAP) trial: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Many women try to stop smoking in pregnancy but fail. One difficulty is that there is insufficient evidence that medications for smoking cessation are effective and safe in pregnancy and thus many women prefer to avoid these. Physical activity (PA) interventions may assist cessation; however, trials examining these interventions have been too small to detect or exclude plausible beneficial effects. The London Exercise And Pregnant smokers (LEAP) trial is investigating whether a PA intervention is effective and cost-effective when used for smoking cessation by pregnant women, and will be the largest study of its kind to date. Methods/design The LEAP study is a pragmatic, multi-center, two-arm, randomized, controlled trial that will target pregnant women who smoke at least one cigarette a day (and at least five cigarettes a day before pregnancy), and are between 10 and 24 weeks pregnant. Eligible patients are individually randomized to either usual care (that is, behavioral support for smoking cessation) or usual care plus a intervention (entailing supervised exercise on a treadmill plus PA consultations). The primary outcome of the trial is self-reported and biochemically validated continuous abstinence from smoking between a specified quit date and the end of pregnancy. The secondary outcomes, measured at 1 and 4 weeks after the quit date, and at the end of pregnancy and 6 months after childbirth, are PA levels, depression, self-confidence, and cigarette withdrawal symptoms. Smoking status will also be self-reported at 6 months after childbirth. In addition, perinatal measures will be collected, including antenatal complications, duration of labor, mode of delivery, and birth and placental weight. Outcomes will be analyzed on an intention-to-treat basis, and logistic regression models used to compare treatment effects on the primary outcome. Discussion This trial will assess whether a PA intervention is effective when used for smoking cessation during

A Fully Automated Diabetes Prevention Program, Alive-PD: Program Design and Randomized Controlled Trial Protocol

PubMed Central

Azar, Kristen MJ; Block, Torin J; Romanelli, Robert J; Carpenter, Heather; Hopkins, Donald; Palaniappan, Latha; Block, Clifford H

2015-01-01

Background In the United States, 86 million adults have pre-diabetes. Evidence-based interventions that are both cost effective and widely scalable are needed to prevent diabetes. Objective Our goal was to develop a fully automated diabetes prevention program and determine its effectiveness in a randomized controlled trial. Methods Subjects with verified pre-diabetes were recruited to participate in a trial of the effectiveness of Alive-PD, a newly developed, 1-year, fully automated behavior change program delivered by email and Web. The program involves weekly tailored goal-setting, team-based and individual challenges, gamification, and other opportunities for interaction. An accompanying mobile phone app supports goal-setting and activity planning. For the trial, participants were randomized by computer algorithm to start the program immediately or after a 6-month delay. The primary outcome measures are change in HbA1c and fasting glucose from baseline to 6 months. The secondary outcome measures are change in HbA1c, glucose, lipids, body mass index (BMI), weight, waist circumference, and blood pressure at 3, 6, 9, and 12 months. Randomization and delivery of the intervention are independent of clinic staff, who are blinded to treatment assignment. Outcomes will be evaluated for the intention-to-treat and per-protocol populations. Results A total of 340 subjects with pre-diabetes were randomized to the intervention (n=164) or delayed-entry control group (n=176). Baseline characteristics were as follows: mean age 55 (SD 8.9); mean BMI 31.1 (SD 4.3); male 68.5%; mean fasting glucose 109.9 (SD 8.4) mg/dL; and mean HbA1c 5.6 (SD 0.3)%. Data collection and analysis are in progress. We hypothesize that participants in the intervention group will achieve statistically significant reductions in fasting glucose and HbA1c as compared to the control group at 6 months post baseline. Conclusions The randomized trial will provide rigorous evidence regarding the efficacy of

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

PubMed

Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

PubMed Central

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

Are outcomes reported in surgical randomized trials patient-important? A systematic review and meta-analysis

PubMed Central

Adie, Sam; Harris, Ian A.; Naylor, Justine M.; Mittal, Rajat

2017-01-01

Background The dangers of using surrogate outcomes are well documented. They may have little or no association with their patient-important correlates, leading to the approval and use of interventions that lack efficacy. We sought to assess whether primary outcomes in surgical randomized controlled trials (RCTs) are more likely to be patient-important outcomes than surrogate or laboratory-based outcomes. Methods We reviewed RCTs assessing an operative intervention published in 2008 and 2009 and indexed in MEDLINE, EMBASE or the Cochrane Central Register of Controlled Trials. After a pilot of the selection criteria, 1 reviewer selected trials and another reviewer checked the selection. We extracted information on outcome characteristics (patient-important, surrogate, or laboratory-based outcome) and whether they were primary or secondary outcomes. We calculated odds ratios (OR) and pooled in random-effects meta-analysis to obtain an overall estimate of the association between patient importance and primary outcome specification. Results In 350 included RCTs, a total of 8258 outcomes were reported (median 18 per trial. The mean proportion (per trial) of patient-important outcomes was 60%, and 66% of trials specified a patient-important primary outcome. The most commonly reported patient-important primary outcomes were morbid events (41%), intervention outcomes (11%), function (11%) and pain (9%). Surrogate and laboratory-based primary outcomes were reported in 33% and 8% of trials, respectively. Patient-important outcomes were not associated with primary outcome status (OR 0.82, 95% confidence interval 0.63–1.1, I2 = 21%). Conclusion A substantial proportion of surgical RCTs specify primary outcomes that are not patient-important. Authors, journals and trial funders should insist that patient-important outcomes are the focus of study. PMID:28234219

Weight management for overweight and obese men delivered through professional football clubs: a pilot randomized trial

PubMed Central

2013-01-01

Background The prevalence of male obesity is increasing, but men are less likely than women to attend existing weight management programmes. We have taken a novel approach to reducing perceived barriers to weight loss for men by using professional football (soccer) clubs to encourage participation in a weight management group programme, gender-sensitised in content and style of delivery. Football Fans in Training (FFIT) provides 12 weeks of weight loss, physical activity and healthy eating advice at top professional football clubs in Scotland. This pilot randomized trial explored the feasibility of using these clubs as a setting for a randomized controlled trial of 12 month weight loss following men’s participation in FFIT. Methods A two-arm pilot trial at two Scottish Premier League football clubs (one large, one smaller), with 103 men (aged 35–65, body mass index (BMI) ≥27 kg/m2) individually randomized to the intervention (n=51, received the pilot programme (p-FFIT) immediately) and waitlist comparison (n=52, received p-FFIT after four months) groups. Feasibility of recruitment, randomization, data collection and retention were assessed. Objective physical measurements (weight, waist circumference, blood pressure, body composition) and questionnaires (self-reported physical activity, diet, alcohol consumption, psychological outcomes) were obtained from both groups by fieldworkers trained to standard protocols at baseline and 12 weeks, and from the intervention group at 6 and 12 months. Qualitative methods elicited men’s experiences of participation in the pilot trial. Results Following a short recruitment period, the recruitment target was achieved at the large, but not smaller, club. Participants’ mean age was 47.1±8.4 years; mean BMI 34.5±5.0 kg/m2. Retention through the trial was good (>80% at 12 weeks and 6 months; >75% at 12 months), and 76% attended at least 80% of available programme delivery sessions. At 12 weeks, the intervention group lost

Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: results from a randomized controlled trial

PubMed Central

2013-01-01

Background Hypertension can be prevented by adopting healthy dietary patterns. Our aim was to assess the 4-year effect on blood pressure (BP) control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern. Methods The PREDIMED primary prevention trial is a randomized, single-blinded, controlled trial conducted in Spanish primary healthcare centers. We recruited 7,447 men (aged 55 to 80 years) and women (aged 60 to 80 years) who had high risk for cardiovascular disease. Participants were assigned to a control group or to one of two Mediterranean diets. The control group received education on following a low-fat diet, while the groups on Mediterranean diets received nutritional education and also free foods; either extra virgin olive oil, or nuts. Trained personnel measured participants’ BP at baseline and once yearly during a 4-year follow-up. We used generalized estimating equations to assess the differences between groups during the follow-up. Results The percentage of participants with controlled BP increased in all three intervention groups (P-value for within-group changes: P<0.001). Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group (−1.53 mmHg (95% confidence interval (CI) −2.01 to −1.04) for the Mediterranean diet supplemented with extra virgin olive oil, and −0.65 mmHg (95% CI -1.15 to −0.15) mmHg for the Mediterranean diet supplemented with nuts). No between-group differences in changes of systolic BP were seen. Conclusions Both the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP. However, we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group. Trial registration Current Controlled Trials ISRCTN35739639 PMID:24050803

Review of Recent Methodological Developments in Group-Randomized Trials: Part 1—Design

PubMed Central

Li, Fan; Gallis, John A.; Prague, Melanie; Murray, David M.

2017-01-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis. PMID:28426295

Micro-Randomized Trials: An Experimental Design for Developing Just-in-Time Adaptive Interventions

PubMed Central

Klasnja, Predrag; Hekler, Eric B.; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

Objective This paper presents an experimental design, the micro-randomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals’ health behaviors. Micro-randomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. Methods The paper describes the micro-randomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Results Micro-randomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Conclusions Micro-randomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions’ effects, enabling creation of more effective JITAIs. PMID:26651463

Reporting Randomized Controlled Trials in Education

ERIC Educational Resources Information Center

Mayo-Wilson, Evan; Grant, Sean; Montgomery, Paul

2014-01-01

Randomized controlled trials (RCTs) are increasingly used to evaluate programs and interventions in order to inform education policy and practice. High quality reports of these RCTs are needed for interested readers to understand the rigor of the study, the interventions tested, and the context in which the evaluation took place (Mayo-Wilson et…

Nurse-Moderated Internet-Based Support for New Mothers: Non-Inferiority, Randomized Controlled Trial

PubMed Central

Reece, Christy E; Bowering, Kerrie; Jeffs, Debra; Sawyer, Alyssa C P; Mittinty, Murthy; Lynch, John W

2017-01-01

Background Internet-based interventions moderated by community nurses have the potential to improve support offered to new mothers, many of whom now make extensive use of the Internet to obtain information about infant care. However, evidence from population-based randomized controlled trials is lacking. Objective The aim of this study was to test the non-inferiority of outcomes for mothers and infants who received a clinic-based postnatal health check plus nurse-moderated, Internet-based group support when infants were aged 1-7 months as compared with outcomes for those who received standard care consisting of postnatal home-based support provided by a community nurse. Methods The design of the study was a pragmatic, preference, non-inferiority randomized control trial. Participants were recruited from mothers contacted for their postnatal health check, which is offered to all mothers in South Australia. Mothers were assigned either (1) on the basis of their preference to clinic+Internet or home-based support groups (n=328), or (2) randomly assigned to clinic+Internet or home-based groups if they declared no strong preference (n=491). The overall response rate was 44.8% (819/1827). The primary outcome was parenting self-competence, as measured by the Parenting Stress Index (PSI) Competence subscale, and the Karitane Parenting Confidence Scale scores. Secondary outcome measures included PSI Isolation, Interpersonal Support Evaluation List–Short Form, Maternal Support Scale, Ages and Stages Questionnaire–Social-Emotional and MacArthur Communicative Development Inventory (MCDI) scores. Assessments were completed offline via self-assessment questionnaires at enrolment (mean child age=4.1 weeks, SD 1.3) and again when infants were aged 9, 15, and 21 months. Results Generalized estimating equations adjusting for post-randomization baseline imbalances showed that differences in outcomes between mothers in the clinic+Internet and home-based support groups did not

Effects of interpretive nutrition labels on consumer food purchases: the Starlight randomized controlled trial.

PubMed

Ni Mhurchu, Cliona; Volkova, Ekaterina; Jiang, Yannan; Eyles, Helen; Michie, Jo; Neal, Bruce; Blakely, Tony; Swinburn, Boyd; Rayner, Mike

2017-03-01

Background: Nutrition labeling is a prominent policy to promote healthy eating. Objective: We aimed to evaluate the effects of 2 interpretive nutrition labels compared with a noninterpretive label on consumer food purchases. Design: In this parallel-group randomized controlled trial, we enrolled household shoppers across New Zealand who owned smartphones and were aged ≥18 y. Eligible participants were randomly assigned (1:1:1) to receive either traffic light labels (TLLs), Health Star Rating labels (HSRs), or a control [nutrition information panel (NIP)]. Smartphone technology allowed participants to scan barcodes of packaged foods and to receive allocated labels on their smartphone screens. The primary outcome was the mean healthiness of all packaged food purchases over the 4-wk intervention period, which was measured by using the Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC). Results: Between October 2014 and November 2015, 1357 eligible shoppers were randomly assigned to TLL ( n = 459), HSR ( n = 443), or NIP ( n = 455) labels. Overall difference in the mean transformed NPSC score for the TLL group compared with the NIP group was -0.20 (95% CI: -0.94, 0.54; P = 0.60). The corresponding difference for HSR compared with NIP was -0.60 (95% CI: -1.35, 0.15; P = 0.12). In an exploratory per-protocol analysis of participants who used the labeling intervention more often than average ( n = 423, 31%), those who were assigned to TLL and HSR had significantly better NPSC scores [TLL compared with NIP: -1.33 (95% CI: -2.63, -0.04; P = 0.04); HSR compared with NIP: -1.70 (95% CI: -2.97, -0.43; P = 0.01)]. Shoppers who were randomly assigned to HSR and TLL also found the labels significantly more useful and easy to understand than the NIP (all P values <0.001). Conclusions: At the relatively low level of use observed in this trial, interpretive nutrition labels had no significant effect on food purchases. However, shoppers who used

Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Garbutt, James C; Kampov-Polevoy, Alexei B; Gallop, Robert; Kalka-Juhl, Linda; Flannery, Barbara A.

2010-01-01

Background Recent clinical trials and case-reports indicate that baclofen, a GABAB agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol dependent individuals in two placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States. Methods The study was a double-blind, placebo-controlled, randomized study comparing 30 mg per day of baclofen to placebo over 12 weeks of treatment and utilizing eight sessions of BRENDA, a low-intensity psychosocial intervention. 121 subjects were screened to yield 80 randomized subjects (44 male) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined. Results 76% of subjects completed the study. No difference by drug condition was seen in % heavy drinking days where on-average rates were 25.5% (± 23.6%) for placebo and 25.9% (± 23.2%) for baclofen during treatment (t(73)=0.59, p=0.56). Similarly, no differences were seen by drug condition in % days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F(1,73)=5.39, p=0.02). Baclofen was well tolerated with only two individuals stopping baclofen because of adverse events. There were no serious adverse events. Conclusions Baclofen, a GABAB agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study)

PubMed Central

2014-01-01

Background There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Methods Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. Results We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Conclusions Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial

The Pittsburgh Randomized Trial of Tacrolimus Compared to Cyclosporine for Hepatic Transplantation

PubMed Central

Fung, John J.; Eliasziw, Michael; Todo, Satoru; Jain, Ashok; Demetris, Anthony J.; McMichael, John P.; Starzl, Thomas E.; Meier, Paul; Donner, Allan

2009-01-01

Background Tacrolimus (formerly FK 506) was first used clinically in 1989 to successfully replace cyclosporine in hepatic transplant recipients who were experiencing intractable rejection or as the baseline drug from the time of operation. After extensive pilot experience, an institutional review board-mandated clinical trial comparing cyclosporine with tacrolimus was performed. Study Design From February 16, 1990 to December 26, 1991, 154 patients were recruited. The competing drugs were combined with equal induction doses of prednisone in both arms of the study for the first 81 patients and with subsequently higher doses of prednisone in the remaining 35 patients who received cyclosporine and were entered into the trial. Drug crossover was permitted for lack of efficacy or adverse events. End points were rejection confirmed by biopsy and treatment failure leading to retransplantation or death. Results Seventy-nine patients were randomized to the tacrolimus arm and 75 to the cyclosporine arm during 1990 and 1991. All patients were available for follow-up throughout the trial, which terminated on May 30, 1995. The mean duration of follow-up was four years. Patients randomized to the tacrolimus arm were less likely to experience acute rejection than were those receiving cyclosporine, with 36.2 percent of the patients receiving tacrolimus and 16.8 percent of the patients receiving cyclosporine showing freedom from rejection at one year (p=0.003, likelihood ratio test). Survival of patients over the course of the study was virtually the same in the two groups. Conclusions Tacrolimus was more effective than cyclosporine in preventing acute rejection. PMID:8696542

Acupuncture for alcohol withdrawal: a randomized controlled trial.

PubMed

Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

2003-01-01

Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

Randomized trials published in Chinese or Western journals: comparative empirical analysis.

PubMed

Purgato, Marianna; Cipriani, Andrea; Barbui, Corrado

2012-06-01

A major concern to the inclusion in systematic reviews of studies originating in China and published in Chinese journals refers to the quality of study reporting. In this systematic survey of randomized trials, we compared the characteristics of studies published in Chinese journals with those of studies published in Western journals. We included 69 studies comparing citalopram with other antidepressant drugs in the treatment of major depression. Of these, 37 (54%) were published in Chinese journals. The standard of reporting was generally poor in both Western and Chinese studies. In some Chinese studies, the generation of the randomization sequence raised concern about their experimental nature, and in almost all included studies, the concealment of allocation was not properly described. Blinding was seldom adopted in Chinese studies, and the risk of sponsorship bias was uncertain because Chinese studies did not report any financial support. In most Western studies, outcome data were selectively and incompletely reported. Pooling together all trials revealed that citalopram was similarly effective in comparison with all other antidepressant drugs both in Western studies (standardized mean difference, -0.04; 95% confidence interval, -0.15 to 0.06) and in Chinese studies (standardized mean difference, -0.08, 95% confidence interval, -0.18 to 0.02). Randomized controlled trials published in Chinese journals represent most of the studies included in this review. This suggests that omitting to search biomedical databases originating from China would systematically exclude a relevant proportion of randomized trials published in Chinese journals, with a risk of random error or bias. The increasing inclusion of Chinese studies in systematic reviews reinforces the need to check the quality of randomized trials that are meta-analyzed.

A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection

PubMed Central

2016-01-01

BACKGROUND Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD). METHODS Beginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days. RESULTS A total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, −15 percentage points; 95% confidence interval, −36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups. CONCLUSIONS In this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified

Recruiting Participants for Randomized Controlled Trials

ERIC Educational Resources Information Center

Gallagher, H. Alix; Roschelle, Jeremy; Feng, Mingyu

2014-01-01

The objective of this study was to look across strategies used in a wide range of studies to build a framework for researchers to use in conceptualizing the recruitment process. This paper harvests lessons learned across 19 randomized controlled trials in K-12 school settings conducted by a leading research organization to identify strategies that…

Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2011-12-01

Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

PubMed Central

2011-01-01

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

A multicenter, randomized controlled trial of immediate total-body CT scanning in trauma patients (REACT-2)

PubMed Central

2012-01-01

Background Computed tomography (CT) scanning has become essential in the early diagnostic phase of trauma care because of its high diagnostic accuracy. The introduction of multi-slice CT scanners and infrastructural improvements made total-body CT scanning technically feasible and its usage is currently becoming common practice in several trauma centers. However, literature provides limited evidence whether immediate total-body CT leads to better clinical outcome then conventional radiographic imaging supplemented with selective CT scanning in trauma patients. The aim of the REACT-2 trial is to determine the value of immediate total-body CT scanning in trauma patients. Methods/design The REACT-2 trial is an international, multicenter randomized clinical trial. All participating trauma centers have a multi-slice CT scanner located in the trauma room or at the Emergency Department (ED). All adult, non-pregnant, severely injured trauma patients according to predefined criteria will be included. Patients in whom direct scanning will hamper necessary cardiopulmonary resuscitation or who require an immediate operation because of imminent death (both as judged by the trauma team leader) are excluded. Randomization will be computer assisted. The intervention group will receive a contrast-enhanced total-body CT scan (head to pelvis) during the primary survey. The control group will be evaluated according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be in-hospital mortality. Secondary outcomes are differences in mortality and morbidity during the first year post trauma, several trauma work-up time intervals, radiation exposure, general health and quality of life at 6 and 12 months post trauma and cost-effectiveness. Discussion The REACT-2 trial is a multicenter randomized clinical trial that will provide evidence on the value of immediate total-body CT scanning during the primary

Random forests of interaction trees for estimating individualized treatment effects in randomized trials.

PubMed

Su, Xiaogang; Peña, Annette T; Liu, Lei; Levine, Richard A

2018-04-29

Assessing heterogeneous treatment effects is a growing interest in advancing precision medicine. Individualized treatment effects (ITEs) play a critical role in such an endeavor. Concerning experimental data collected from randomized trials, we put forward a method, termed random forests of interaction trees (RFIT), for estimating ITE on the basis of interaction trees. To this end, we propose a smooth sigmoid surrogate method, as an alternative to greedy search, to speed up tree construction. The RFIT outperforms the "separate regression" approach in estimating ITE. Furthermore, standard errors for the estimated ITE via RFIT are obtained with the infinitesimal jackknife method. We assess and illustrate the use of RFIT via both simulation and the analysis of data from an acupuncture headache trial. Copyright © 2018 John Wiley & Sons, Ltd.

Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

PubMed

Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

2012-06-01

Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

Insufflation with Humidified and Heated Carbon Dioxide in Short-Term Laparoscopy: A Double-Blinded Randomized Controlled Trial

PubMed Central

Herrmann, Anja; De Wilde, Rudy Leon

2015-01-01

Background. We tested the hypothesis that warm-humidified carbon dioxide (CO2) insufflation would reduce postoperative pain and morphine requirement compared to cold-dry CO2 insufflation. Methods. A double-blinded, randomized, controlled trial was conducted to compare warm, humidified CO2 and cold-dry CO2. Patients with benign uterine diseases were randomized to either treatment (n = 48) or control (n = 49) group during laparoscopically assisted vaginal hysterectomy. Primary endpoints of the study were rest pain, movement pain, shoulder-tip pain, and cough pain at 2, 4, 6, 24, and 48 hours postoperatively, measured by visual analogue scale. Secondary outcomes were morphine consumption, rejected boli, temperature change, recovery room stay, and length of hospital stay. Results. There were no significant differences in all baseline characteristics. Shoulder-tip pain at 6 h postoperatively was significantly reduced in the intervention group. Pain at rest, movement pain, and cough pain did not differ. Total morphine consumption and rejected boli at 24 h postoperatively were significantly higher in the control group. Temperature change, recovery room stay, and length of hospital were similar. Conclusions. Warm, humidified insufflation gas significantly reduces postoperative shoulder-tip pain as well as morphine demand. This trial is registered with Clinical Trial Registration Number   DRKS00003853 (German Clinical Trials Register (DRKS)). PMID:25722977

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

PubMed Central

Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

2015-01-01

Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis

Implementation research design: integrating participatory action research into randomized controlled trials

PubMed Central

Leykum, Luci K; Pugh, Jacqueline A; Lanham, Holly J; Harmon, Joel; McDaniel, Reuben R

2009-01-01

Background A gap continues to exist between what is known to be effective and what is actually delivered in the usual course of medical care. The goal of implementation research is to reduce this gap. However, a tension exists between the need to obtain generalizeable knowledge through implementation trials, and the inherent differences between healthcare organizations that make standard interventional approaches less likely to succeed. The purpose of this paper is to explore the integration of participatory action research and randomized controlled trial (RCT) study designs to suggest a new approach for studying interventions in healthcare settings. Discussion We summarize key elements of participatory action research, with particular attention to its collaborative, reflective approach. Elements of participatory action research and RCT study designs are discussed and contrasted, with a complex adaptive systems approach used to frame their integration. Summary The integration of participatory action research and RCT design results in a new approach that reflects not only the complex nature of healthcare organizations, but also the need to obtain generalizeable knowledge regarding the implementation process. PMID:19852784

Whole body vibration for older persons: an open randomized, multicentre, parallel, clinical trial

PubMed Central

2011-01-01

Background Institutionalized older persons have a poor functional capacity. Including physical exercise in their routine activities decreases their frailty and improves their quality of life. Whole-body vibration (WBV) training is a type of exercise that seems beneficial in frail older persons to improve their functional mobility, but the evidence is inconclusive. This trial will compare the results of exercise with WBV and exercise without WBV in improving body balance, muscle performance and fall prevention in institutionalized older persons. Methods/Design An open, multicentre and parallel randomized clinical trial with blinded assessment. 160 nursing home residents aged over 65 years and of both sexes will be identified to participate in the study. Participants will be centrally randomised and allocated to interventions (vibration or exercise group) by telephone. The vibration group will perform static/dynamic exercises (balance and resistance training) on a vibratory platform (Frequency: 30-35 Hz; Amplitude: 2-4 mm) over a six-week training period (3 sessions/week). The exercise group will perform the same exercise protocol but without a vibration stimuli platform. The primary outcome measure is the static/dynamic body balance. Secondary outcomes are muscle strength and, number of new falls. Follow-up measurements will be collected at 6 weeks and at 6 months after randomization. Efficacy will be analysed on an intention-to-treat (ITT) basis and 'per protocol'. The effects of the intervention will be evaluated using the "t" test, Mann-Witney test, or Chi-square test, depending on the type of outcome. The final analysis will be performed 6 weeks and 6 months after randomization. Discussion This study will help to clarify whether WBV training improves body balance, gait mobility and muscle strength in frail older persons living in nursing homes. As far as we know, this will be the first study to evaluate the efficacy of WBV for the prevention of falls. Trial

[Lower Uterine Segment Trial: A pragmatic open multicenter randomized trial].

PubMed

Rozenberg, P; Deruelle, P; Sénat, M-V; Desbrière, R; Winer, N; Simon, E; Ville, Y; Kayem, G; Boutron, I

2018-04-01

The data from literature show that trial of labor and elective repeat cesarean delivery after a prior cesarean delivery both present significant risks and benefits, and these risks and benefits differ for the woman and her fetus. The benefits to the woman can be at the expense of her fetus and vice-versa. This uncertainty is compounded by the scarcity of high-level evidence that preclude accurate quantification of the risks and benefits that could help provide a fair counseling about a trial of labor and elective repeat cesarean delivery. An interesting way of research is to evaluate the potential benefits of a decision rule associated to the ultrasound measurement of the lower uterine segment (LUS). Indeed, ultrasonography may be helpful in determining a specific risk for a given patient by measuring the thickness of the LUS, i,e, the thickness of the cesarean delivery scar area. Although only small and often methodologically biased data have been published, they look promising as their results are concordant: ultrasonographic measurements of the LUS thickness is highly correlated with the intraoperative findings at cesarean delivery. Furthermore, the thinner the LUS becomes on ultrasound, the higher the likelihood of a defect in the LUS. Finally, ultrasound assessment of LUS has an excellent negative predictive value for the risk of uterine defect. Therefore, this exam associated with a rule of decision could help to reduce the rate of elective repeat cesarean delivery and especially to reduce the fetal and maternal mortality and morbidity related to trial of labor after a prior cesarean delivery. This is a pragmatic open multicenter randomized trial with two parallel arms. Randomization will be centralized and computerized. Since blindness is impossible, an adjudication committee will evaluate the components of the primary composite outcome in order to avoid evaluation bias. An interim analysis will be planned mid-strength of the trial. Ultrasound will be

Intention-to-treat analysis and accounting for missing data in orthopaedic randomized clinical trials.

PubMed

Herman, Amir; Botser, Itamar Busheri; Tenenbaum, Shay; Chechick, Ahron

2009-09-01

The intention-to-treat principle implies that all patients who are randomized in a clinical trial should be analyzed according to their original allocation. This means that patients crossing over to another treatment group and patients lost to follow-up should be included in the analysis as a part of their original group. This principle is important for preserving the randomization scheme, which is the basis for correct inference in any randomized trial. In this study, we examined the use of the intention-to-treat principle in recently published orthopaedic clinical trials. We surveyed eight leading orthopaedic journals for randomized clinical trials published between January 2005 and August 2008. We determined whether the intention-to-treat principle was implemented and, if so, how it was used in each trial. Specifically, we ascertained which methods were used to account for missing data. Our search yielded 274 randomized clinical trials, and the intention-to-treat principle was used in ninety-six (35%) of them. There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; this practice was most notable in studies of surgical interventions. The most popular method of adjusting for missing data was the "last observation carried forward" technique. In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission might introduce bias to

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

PubMed

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

2017-01-01

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

Sino-implant (II) - a levonorgestrel-releasing two-rod implant: systematic review of the randomized controlled trials

PubMed Central

Steiner, Markus J.; Lopez, Laureen M.; Grimes, David A.; Cheng, Linan; Shelton, Jim; Trussell, James; Farley, Timothy M.M.; Dorflinger, Laneta

2013-01-01

Background Sino-implant (II) is a subdermal contraceptive implant manufactured in China. This two-rod levonorgestrel-releasing implant has the same amount of active ingredient (150 mg levonorgestrel) and mechanism of action as the widely available contraceptive implant Jadelle. We examined randomized controlled trials of Sino-implant (II) for effectiveness and side effects. Study design We searched electronic databases for studies of Sino-implant (II), and then restricted our review to randomized controlled trials. The primary outcome of this review was pregnancy. Results Four randomized trials with a total of 15,943 women assigned to Sino-implant (II) had first-year probabilities of pregnancy ranging from 0.0% to 0.1%. Cumulative probabilities of pregnancy during the four years of the product's approved duration of use were 0.9% and 1.06% in the two trials that presented date for four-year use. Five-year cumulative probabilities of pregnancy ranged from 0.7% to 2.1%. In one trial, the cumulative probability of pregnancy more than doubled during the fifth year (from 0.9% to 2.1%), which may be why the implant is approved for four years of use in China. Five-year cumulative probabilities of discontinuation due to menstrual problems ranged from 12.5% to 15.5% for Sino-implant (II). Conclusions Sino-implant (II) is one of the most effective contraceptives available today. These available clinical data, combined with independent laboratory testing, and the knowledge that 7 million women have used this method since 1994, support the safety and effectiveness of Sino-implant (II). The lower cost of Sino-implant (II) compared with other subdermal implants could improve access to implants in resource-constrained settings. PMID:20159174

Alternatives to the Randomized Controlled Trial

PubMed Central

West, Stephen G.; Duan, Naihua; Pequegnat, Willo; Gaist, Paul; Des Jarlais, Don C.; Holtgrave, David; Szapocznik, José; Fishbein, Martin; Rapkin, Bruce; Clatts, Michael; Mullen, Patricia Dolan

2008-01-01

Public health researchers are addressing new research questions (e.g., effects of environmental tobacco smoke, Hurricane Katrina) for which the randomized controlled trial (RCT) may not be a feasible option. Drawing on the potential outcomes framework (Rubin Causal Model) and Campbellian perspectives, we consider alternative research designs that permit relatively strong causal inferences. In randomized encouragement designs, participants are randomly invited to participate in one of the treatment conditions, but are allowed to decide whether to receive treatment. In quantitative assignment designs, treatment is assigned on the basis of a quantitative measure (e.g., need, merit, risk). In observational studies, treatment assignment is unknown and presumed to be nonrandom. Major threats to the validity of each design and statistical strategies for mitigating those threats are presented. PMID:18556609

Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial

PubMed Central

2011-01-01

Background There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. Methods/Design In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. Discussion The result of this trial will assess the efficacy of using

Carotid artery stenting vs. carotid endarterectomy in the management of carotid artery stenosis: Lessons learned from randomized controlled trials

PubMed Central

Salem, Mohamed M.; Alturki, Abdulrahman Y.; Fusco, Matthew R.; Thomas, Ajith J.; Carter, Bob S.; Chen, Clark C.; Kasper, Ekkehard M.

2018-01-01

Background: Carotid artery stenosis, both symptomatic and asymptomatic, has been well studied with several multicenter randomized trials. The superiority of carotid endarterectomy (CEA) to medical therapy alone in both symptomatic and asymptomatic carotid artery stenosis has been well established in previous trials in the 1990s. The consequent era of endovascular carotid artery stenting (CAS) has offered another option for treating carotid artery stenosis. A series of randomized trials have now been conducted to compare CEA and CAS in the treatment of carotid artery disease. The large number of similar trials has created some confusion due to inconsistent results. Here, the authors review the trials that compare CEA and CAS in the management of carotid artery stenosis. Methods: The PubMed database was searched systematically for randomized controlled trials published in English that compared CEA and CAS. Only human studies on adult patients were assessed. The references of identified articles were reviewed for additional manuscripts to be included if inclusion criteria were met. The following terms were used during search: carotid stenosis, endarterectomy, stenting. Retrospective or single-center studies were excluded from the review. Results: Thirteen reports of seven large-scale prospective multicenter studies, comparing both interventions for symptomatic or asymptomatic extracranial carotid artery stenosis, were identified. Conclusions: While the superiority of intervention to medical management for symptomatic patients has been well established in the literatures, careful selection of asymptomatic patients for intervention should be undertaken and only be pursued after institution of appropriate medical therapy until further reports on trials comparing medical therapy to intervention in this patient group are available. PMID:29740506

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials.

PubMed

Salinas, R; Counsell, C; Prasad, K; Gelband, H; Garner, P

1999-11-01

To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.

Non-pharmacological care for patients with generalized osteoarthritis: design of a randomized clinical trial

PubMed Central

2010-01-01

Background Non-pharmacological treatment (NPT) is a useful treatment option in the management of hip or knee osteoarthritis. To our knowledge however, no studies have investigated the effect of NPT in patients with generalized osteoarthritis (GOA). The primary aim of this study is to compare the effectiveness of two currently existing health care programs with different intensity and mode of delivery on daily functioning in patients with GOA. The secondary objective is to compare the cost-effectiveness of both interventions. Methods/Design In this randomized, single blind, clinical trial with active controls, we aim to include 170 patients with GOA. The experimental intervention consist of six self-management group sessions provided by a multi-disciplinary team (occupational therapist, physiotherapist, dietician and specialized nurse). The active control group consists of two group sessions and four sessions by telephone, provided by a specialized nurse and physiotherapist. Both therapies last six weeks. Main study outcome is daily functioning during the first year after the treatment, assessed on the Health Assessment Questionnaire. Secondary outcomes are health related quality of life, specific complaints, fatigue, and costs. Illness cognitions, global perceived effect and self-efficacy, will also be assessed for a responder analysis. Outcome assessments are performed directly after the intervention, after 26 weeks and after 52 weeks. Discussion This article describes the design of a randomized, single blind, clinical trial with a one year follow up to compare the costs and effectiveness of two non-pharmacological interventions with different modes of delivery for patients with GOA. Trial registration Dutch Trial Register NTR2137 PMID:20594308

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

DTIC Science & Technology

2017-10-01

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

Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available.

PubMed

Hernán, Miguel A; Robins, James M

2016-04-15

Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Empirical likelihood inference in randomized clinical trials.

PubMed

Zhang, Biao

2017-01-01

In individually randomized controlled trials, in addition to the primary outcome, information is often available on a number of covariates prior to randomization. This information is frequently utilized to undertake adjustment for baseline characteristics in order to increase precision of the estimation of average treatment effects; such adjustment is usually performed via covariate adjustment in outcome regression models. Although the use of covariate adjustment is widely seen as desirable for making treatment effect estimates more precise and the corresponding hypothesis tests more powerful, there are considerable concerns that objective inference in randomized clinical trials can potentially be compromised. In this paper, we study an empirical likelihood approach to covariate adjustment and propose two unbiased estimating functions that automatically decouple evaluation of average treatment effects from regression modeling of covariate-outcome relationships. The resulting empirical likelihood estimator of the average treatment effect is as efficient as the existing efficient adjusted estimators 1 when separate treatment-specific working regression models are correctly specified, yet are at least as efficient as the existing efficient adjusted estimators 1 for any given treatment-specific working regression models whether or not they coincide with the true treatment-specific covariate-outcome relationships. We present a simulation study to compare the finite sample performance of various methods along with some results on analysis of a data set from an HIV clinical trial. The simulation results indicate that the proposed empirical likelihood approach is more efficient and powerful than its competitors when the working covariate-outcome relationships by treatment status are misspecified.

The prompted optional randomization trial: a new design for comparative effectiveness research.

PubMed

Flory, James; Karlawish, Jason

2012-12-01

Randomized controlled trials are the gold standard for medical evidence because randomization provides the best-known protection against confounding of results. Randomization has practical and ethical problems that limit the number of trials that can be conducted, however. A different method for collecting clinical data retains the statistically useful properties of randomization without incurring its practical and ethical challenges. A computerized prompt introduces a random element into clinical decision-making that can be instantly overridden if it conflicts with optimal patient care. This creates a weak form of randomization that still eliminates the effect of all confounders, can be carried out without disturbing routine clinical care, and arguably will not require research-grade informed consent.

Delivering successful randomized controlled trials in surgery: Methods to optimize collaboration and study design.

PubMed

Blencowe, Natalie S; Cook, Jonathan A; Pinkney, Thomas; Rogers, Chris; Reeves, Barnaby C; Blazeby, Jane M

2017-04-01

Randomized controlled trials in surgery are notoriously difficult to design and conduct due to numerous methodological and cultural challenges. Over the last 5 years, several UK-based surgical trial-related initiatives have been funded to address these issues. These include the development of Surgical Trials Centers and Surgical Specialty Leads (individual surgeons responsible for championing randomized controlled trials in their specialist fields), both funded by the Royal College of Surgeons of England; networks of research-active surgeons in training; and investment in methodological research relating to surgical randomized controlled trials (to address issues such as recruitment, blinding, and the selection and standardization of interventions). This article discusses these initiatives more in detail and provides exemplar cases to illustrate how the methodological challenges have been tackled. The initiatives have surpassed expectations, resulting in a renaissance in surgical research throughout the United Kingdom, such that the number of patients entering surgical randomized controlled trials has doubled.

The effects of reducing worry in patients with persecutory delusions: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Our approach to advancing the treatment of psychosis is to focus on key single symptoms and develop interventions that target the mechanisms that maintain them. In our theoretical research we have found worry to be an important factor in the development and maintenance of persecutory delusions. Worry brings implausible ideas to mind, keeps them there, and makes the experience distressing. Therefore the aim of the trial is to test the clinical efficacy of a cognitive-behavioral intervention for worry for patients with persecutory delusions and determine how the worry treatment might reduce delusions. Methods/Design An explanatory randomized controlled trial - called the Worry Intervention Trial (WIT) - with 150 patients with persecutory delusions will be carried out. Patients will be randomized to the worry intervention in addition to standard care or to standard care. Randomization will be carried out independently, assessments carried out single-blind, and therapy competence and adherence monitored. The study population will be individuals with persecutory delusions and worry in the context of a schizophrenia spectrum diagnosis. They will not have responded adequately to previous treatment. The intervention is a six-session cognitive-behavioral treatment provided over eight weeks. The control condition will be treatment as usual, which is typically antipsychotic medication and regular appointments. The principal hypotheses are that a worry intervention will reduce levels of worry and that it will also reduce the persecutory delusions. Assessments will be carried out at 0 weeks (baseline), 8 weeks (post treatment) and 24 weeks (follow-up). The statistical analysis strategy will follow the intention-to-treat principle and involve the use of linear mixed models to evaluate and estimate the relevant between- and within-subjects effects (allowing for the possibility of missing data). Both traditional regression and newer instrumental variables analyses will

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

PubMed

Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

2017-07-01

Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Efficacy of smoking prevention program 'Smoke-free Kids': study protocol of a randomized controlled trial

PubMed Central

2009-01-01

Background A strong increase in smoking is noted especially among adolescents. In the Netherlands, about 5% of all 10-year olds, 25% of all 13-year olds and 62% of all 17-year olds report ever smoking. In the U.S., an intervention program called 'Smoke-free Kids' was developed to prevent children from smoking. The present study aims to assess the effects of this home-based smoking prevention program in the Netherlands. Methods/Design A randomized controlled trial is conducted among 9 to 11-year old children of primary schools. Participants are randomly assigned to the intervention and control conditions. The intervention program consists of five printed activity modules designed to improve parenting skills specific to smoking prevention and parent-child communication regarding smoking. These modules will include additional sheets with communication tips. The modules for the control condition will include solely information on smoking and tobacco use. Initiation of cigarette smoking (first instance of puffing on a lighted cigarette), susceptibility to cigarette smoking, smoking-related cognitions, and anti-smoking socialization will be the outcome measures. To collect the data, telephone interviews with mothers as well as with their child will be conducted at baseline. Only the children will be examined at post-intervention follow-ups (6, 12, 24, and 36 months after the baseline). Discussion This study protocol describes the design of a randomized controlled trial that will evaluate the effectiveness of a home-based smoking prevention program. We expect that a significantly lower number of children will start smoking in the intervention condition compared to control condition as a direct result of this intervention. If the program is effective, it is applicable in daily live, which will facilitate implementation of the prevention protocol. Trial registration Netherlands Trial Register NTR1465 PMID:20025727

HIV salvage therapy does not require nucleoside reverse transcriptase inhibitors: a randomized trial

PubMed Central

Tashima, Karen T; Smeaton, Laura M; Fichtenbaum, Carl J; Andrade, Adriana; Eron, Joseph J; Gandhi, Rajesh T; Johnson, Victoria A; Klingman, Karin L; Ritz, Justin; Hodder, Sally; Santana, Jorge L; Wilkin, Timothy; Haubrich, Richard H

2015-01-01

Background Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral (ARV) regimens in treatment-experienced patients in the absence of data from randomized trials. Objective To compare treatment success between participants who omit versus Add NRTIs to an optimized ARV regimen of three or more agents. Design Multisite, randomized, controlled trial. Setting Outpatient HIV clinics. Participants HIV-infected patients with three-class ARV experience and/or viral resistance. Intervention Open-label optimized regimens (not including NRTIs) were selected based upon treatment history and susceptibility testing. Participants were randomized to Omit or Add NRTIs. Measurements The primary efficacy outcome was regimen failure through week 48, using a non-inferiority margin of 15%. The primary safety outcome was time to initial episode of severe sign/symptom or laboratory abnormality prior to discontinuation of NRTI assignment. Results 360 participants were randomized and 93% completed a week 48 visit. The cumulative probability of regimen failure was 29.8% in the Omit NRTI arm versus 25.9% in the Add NRTI arm (difference= 3.2%: 95% CI, −6.1 to 12.5). There were no significant differences in the primary safety endpoints or the proportion of participants with HIV RNA <50 copies/mL between arms. No deaths occurred in the Omit NRTIs arm, compared with 7 deaths in the Add NRTIs arm. Limitations Non-blinded study design and may not be applicable to resource poor settings. Conclusion HIV-infected treatment-experienced patients starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population. PMID:26595748

Web-Based Mindfulness Intervention in Heart Disease: A Randomized Controlled Trial

PubMed Central

Younge, John O.; Wery, Machteld F.; Gotink, Rinske A.; Utens, Elisabeth M. W. J.; Michels, Michelle; Rizopoulos, Dimitris; van Rossum, Elisabeth F. C.

2015-01-01

Background Evidence is accumulating that mindfulness training has favorable effects on psychological outcomes, but studies on physiological outcomes are limited. Patients with heart disease have a high incidence of physiological and psychological problems and may benefit from mindfulness training. Our aim was to determine the beneficial physiological and psychological effects of online mindfulness training in patients with heart disease. Methods The study was a pragmatic randomized controlled single-blind trial. Between June 2012 and April 2014 we randomized 324 patients (mean age 43.2 years, 53.7% male) with heart disease in a 2:1 ratio (n = 215 versus n = 109) to a 12-week online mindfulness training in addition to usual care (UC) compared to UC alone. The primary outcome was exercise capacity measured with the 6 minute walk test (6MWT). Secondary outcomes were other physiological parameters (heart rate, blood pressure, respiratory rate, and NT-proBNP), subjective health status (SF-36), perceived stress (PSS), psychological well-being (HADS), social support (PSSS12) and a composite endpoint (all-cause mortality, heart failure, symptomatic arrhythmia, cardiac surgery, and percutaneous cardiac intervention). Linear mixed models were used to evaluate differences between groups on the repeated outcome measures. Results Compared to UC, mindfulness showed a borderline significant improved 6MWT (effect size, meters: 13.2, 95%CI: -0.02; 26.4, p = 0.050). There was also a significant lower heart rate in favor of the mindfulness group (effect size, beats per minute: -2.8, 95%CI: -5.4;-0.2, p = 0.033). No significant differences were seen on other outcomes. Conclusions Mindfulness training showed positive effects on the physiological parameters exercise capacity and heart rate and it might therefore be a useful adjunct to current clinical therapy in patients with heart disease. Trial Registration Dutch Trial Register 3453 PMID:26641099

Methodological quality of randomized trials published in the Journal of the American Podiatric Medical Association, 1999-2013.

PubMed

Landorf, Karl B; Menz, Hylton B; Armstrong, David G; Herbert, Robert D

2015-07-01

Randomized trials must be of high methodological quality to yield credible, actionable findings. The main aim of this project was to evaluate whether there has been an improvement in the methodological quality of randomized trials published in the Journal of the American Podiatric Medical Association (JAPMA). Randomized trials published in JAPMA during a 15-year period (January 1999 to December 2013) were evaluated. The methodological quality of randomized trials was evaluated using the PEDro scale (scores range from 0 to 10, with 0 being lowest quality). Linear regression was used to assess changes in methodological quality over time. A total of 1,143 articles were published in JAPMA between January 1999 and December 2013. Of these, 44 articles were reports of randomized trials. Although the number of randomized trials published each year increased, there was only minimal improvement in their methodological quality (mean rate of improvement = 0.01 points per year). The methodological quality of the trials studied was typically moderate, with a mean ± SD PEDro score of 5.1 ± 1.5. Although there were a few high-quality randomized trials published in the journal, most (84.1%) scored between 3 and 6. Although there has been an increase in the number of randomized trials published in JAPMA, there is substantial opportunity for improvement in the methodological quality of trials published in the journal. Researchers seeking to publish reports of randomized trials should seek to meet current best-practice standards in the conduct and reporting of their trials.

Effective Recruitment of Schools for Randomized Clinical Trials: Role of School Nurses.

PubMed

Petosa, R L; Smith, L

2017-01-01

In school settings, nurses lead efforts to improve the student health and well-being to support academic success. Nurses are guided by evidenced-based practice and data to inform care decisions. The randomized controlled trial (RCT) is considered the gold standard of scientific rigor for clinical trials. RCTs are critical to the development of evidence-based health promotion programs in schools. The purpose of this article is to present practical solutions to implementing principles of randomization to RCT trials conducted in school settings. Randomization is a powerful sampling method used to build internal and external validity. The school's daily organization and educational mission provide several barriers to randomization. Based on the authors' experience in conducting school-based RCTs, they offer a host of practical solutions to working with schools to successfully implement randomization procedures. Nurses play a critical role in implementing RCTs in schools to promote rigorous science in support of evidence-based practice.

Clinical Trial: High-Dose Acid Suppression for Chronic Cough: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Shaheen, Nicholas J.; Crockett, Seth D.; Bright, Stephanie D.; Madanick, Ryan D.; Buckmire, Robert; Couch, Marion; Dellon, Evan S.; Galanko, Joseph A.; Sharpless, Ginny; Morgan, Douglas R.; Spacek, Melissa B.; Heidt-Davis, Paris; Henke, David

2011-01-01

Summary Background Cough may be a manifestation of gastro-esophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. Aim To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Methods Subjects were non-smokers without history of asthma, with chronic cough for > 8 weeks. All subjects underwent a baseline 24 hr pH/impedance study, methacholine challenge test (MCT), and laryngoscopy. Subjects were randomized to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores, and change in laryngeal findings. Results 40 subjects were randomized (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8, vs. 5.9 in placebo, p = 0.3), or Fisman Cough Severity/Frequency scores. The proportion of patients who improved by >1 standard deviation on the CQLQ was 27.8% (5/18) and 31.8% (7/22) in the placebo and PPI groups respectively. Conclusions In subjects with chronic cough and rare or no heartburn, high-dose PPI did not improve cough-related quality of life or symptoms in this randomized controlled trial. PMID:21083673

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

PubMed

Epperson, C Neill; Terman, Michael; Terman, Jiuan Su; Hanusa, Barbara H; Oren, Dan A; Peindl, Kathleen S; Wisner, Katherine L

2004-03-01

Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery

PubMed Central

Seiler, CM; Fröhlich, BE; Veit, JA; Gazyakan, E; Wente, MN; Wollermann, C; Deckert, A; Witte, S; Victor, N; Buchler, MW; Knaebel, HP

2006-01-01

Background Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. Methods/design CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. Discussion As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice. PMID:16948853

Experiences of randomization: interviews with patients and clinicians in the SPCG-IV trial.

PubMed

Bill-Axelson, Anna; Christensson, Anna; Carlsson, Marianne; Norlén, Bo Johan; Holmberg, Lars

2008-01-01

Recruitment of both patients and clinicians to randomized trials is difficult. Low participation carries the risk of terminating studies early and making them invalid owing to insufficient statistical power. This study investigated patients' and clinicians' experiences of randomization with the aim of facilitating trial participation in the future. This was a qualitative study using content analysis. Patients offered to participate in a randomized trial and randomizing clinicians were interviewed. Five participants, four non-participants and five randomizing clinicians were interviewed, 2-8 years from randomization. Clinicians used strategies in interaction with the patients to facilitate decision making. Patients' attitudes differed and experiences of relatives or friends were often stated as reasons for treatment preferences. Patients described that letting chance decide treatment was a difficult barrier to overcome for randomization. The clinicians used a number of different strategies perceived to make randomization more acceptable to their patients. The clinicians' own motivation for randomizing patients for trials depended on the medical relevance of the study question and the clinicians' major obstacle was to maintain equipoise over time. Regular meetings with the study group helped to maintain equipoise and motivation. To establish a good platform for randomization the clinician needs to know about the patient's treatment preferences and the patient's attitude concerning the role of the clinician to facilitate decision making. The strategies used by the clinicians were perceived as helpful and could be tested in an intervention study.

Diarrhea and dengue control in rural primary schools in Colombia: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Diarrheal diseases and dengue fever are major global health problems. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Poor household water management and sanitation are therefore potential determinants of both diseases. Little is known of the role of stored water for the combined risk of diarrhea and dengue, yet a joint role would be important for developing integrated control and management efforts. Even less is known of the effect of integrating control of these diseases in school settings. The objective of this trial was to investigate whether interventions against diarrhea and dengue will significantly reduce diarrheal disease and dengue entomological risk factors in rural primary schools. Methods/design This is a 2×2 factorial cluster randomized controlled trial. Eligible schools were rural primary schools in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Eligible pupils were school children in grades 0 to 5. Schools were randomized to one of four study arms: diarrhea interventions (DIA); dengue interventions (DEN); combined diarrhea and dengue interventions (DIADEN); and control (C). Schools were allocated publicly in each municipality (strata) at the start of the trial, obviating the need for allocation concealment. The primary outcome for diarrhea is incidence rate of diarrhea in school children and for dengue it is density of adult female Aedes aegypti per school. Approximately 800 pupils from 34 schools were enrolled in the trial with eight schools in the DIA arm, nine in the DEN, eight in the DIADEN, and nine in the control arms. The trial status as of June 2012 was: completed baseline data collections; enrollment, randomization, and allocation of schools. The trial was funded by the Research Council of Norway and the Lazos de Calandaima Foundation

Resistant hypertension optimal treatment trial: a randomized controlled trial.

PubMed

Krieger, Eduardo M; Drager, Luciano F; Giorgi, Dante Marcelo Artigas; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Barreto-Filho, José Augusto Soares; da Rocha Nogueira, Armando; Mill, José Geraldo

2014-01-01

The prevalence of resistant hypertension (ReHy) is not well established. Furthermore, diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and calcium channel blockers are largely used as the first 3-drug combinations for treating ReHy. However, the fourth drug to be added to the triple regimen is still controversial and guided by empirical choices. We sought (1) to determine the prevalence of ReHy in patients with stage II hypertension; (2) to compare the effects of spironolactone vs clonidine, when added to the triple regimen; and (3) to evaluate the role of measuring sympathetic and renin-angiotensin-aldosterone activities in predicting blood pressure response to spironolactone or clonidine. The Resistant Hypertension Optimal Treatment (ReHOT) study (ClinicalTrials.gov NCT01643434) is a prospective, multicenter, randomized trial comprising 26 sites in Brazil. In step 1, 2000 patients will be treated according to hypertension guidelines for 12 weeks, to detect the prevalence of ReHy. Medical therapy adherence will be checked by pill count monitoring. In step 2, patients with confirmed ReHy will be randomized to an open label 3-month treatment with spironolactone (titrating dose, 12.5-50 mg once daily) or clonidine (titrating dose, 0.1-0.3 mg twice daily). The primary endpoint is the effective control of blood pressure after a 12-week randomized period of treatment. The ReHOT study will disseminate results about the prevalence of ReHy in stage II hypertension and the comparison of spironolactone vs clonidine for blood pressure control in patients with ReHy under 3-drug standard regimen. © 2013 Wiley Periodicals, Inc.

Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women’s Health Initiative Randomized Clinical Trial

PubMed Central

Ritenbaugh, Cheryl; Stanford, Janet L.; Wu, LieLing; Shikany, James M.; Schoen, Robert E.; Stefanick, Marcia L.; Taylor, Vicky; Garland, Cedric; Frank, Gail; Lane, Dorothy; Mason, Ellen; McNeeley, S. Gene; Ascensao, Joao; Chlebowski, Rowan T.

2010-01-01

Background In separate Women’s Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine survival of women following colorectal cancer diagnosis in the latter trial. Participants and Methods 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/day) or matching placebo. Colorectal cancer incidence was a component of the study’s monitoring global index but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined but information on their use was collected. Results After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group (hazard ratio [HR] 1.12, 95% Confidence Interval [CI] 0.77–1.63). Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34 % compared to 30 % in the placebo group (HR 1.34, 95% CI 0.58–3.19). Conclusions In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis. PMID:18829444

In Defense of the Randomized Controlled Trial for Health Promotion Research

PubMed Central

Rosen, Laura; Manor, Orly; Engelhard, Dan; Zucker, David

2006-01-01

The overwhelming evidence about the role lifestyle plays in mortality, morbidity, and quality of life has pushed the young field of modern health promotion to center stage. The field is beset with intense debate about appropriate evaluation methodologies. Increasingly, randomized designs are considered inappropriate for health promotion research. We have reviewed criticisms against randomized trials that raise philosophical and practical issues, and we will show how most of these criticisms can be overcome with minor design modifications. By providing rebuttal to arguments against randomized trials, our work contributes to building a sound methodological base for health promotion research. PMID:16735622

[Report quality of randomized controlled trials of moxibustion for knee osteoarthritis based on CONSORT and STRICTOM].

PubMed

Xiong, Jun; Zhu, Daocheng; Chen, Rixin; Ye, Wenguo

2015-08-01

The report quality of randomized controlled trials (RCTs) of moxibustion for knee osteoarthritis (KOA) in China was evaluated by Consolidated Standards for Reporting of Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Moxibustion (STRICTOM). Computer and manual retrieval was used. Four databases of China National Knowledge Infrastructure (CNKD, China Biomedicine (CBM), VIP and WNFANG were searched in combination with manual retrieval for relevant journals to screen the literature that: met the inclusive criteria, and CONSORT and STRICTOM were used to assess the report quality. A total of 52 RCTs were included. It was found that unclear description of random methods, low use of blind methods, no allocation concealment, no sample size calculation, no intention-to-treat analysis,inadequate report of moxibustion details and no mention of practitioners background existed in the majority of the RCTs. Although the quality of RCTs of moxibustion for KOA was generally low, reducing the reliability and homogeneous comparability of the reports ,the quality of heat-sensitive moxibustion RCTs was high. It was believed that in order to improve the reliability and quality of RCTs of moxibustion, CONSORT and STRICTOM should be introduced into the RCT design of moxibustion and be strictly performed.

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

PubMed Central

2012-01-01

Background Caregivers of relatives with Alzheimer’s disease are highly stressed and at risk for physical and psychiatric conditions. Interventions are usually focused on providing caregivers with knowledge of dementia, skills, and/or support, to help them cope with the stress. This model, though true to a certain extent, ignores how caregiver stress is construed in the first place. Besides burden, caregivers also report rewards, uplifts, and gains, such as a sense of purpose and personal growth. Finding benefits through positive reappraisal may offset the effect of caregiving on caregiver outcomes. Design Two randomized controlled trials are planned. They are essentially the same except that Trial 1 is a cluster trial (that is, randomization based on groups of participants) whereas in Trial 2, randomization is based on individuals. Participants are randomized into three groups - benefit finding, psychoeducation, and simplified psychoeducation. Participants in each group receive a total of approximately 12 hours of training either in group or individually at home. Booster sessions are provided at around 14 months after the initial treatment. The primary outcomes are caregiver stress (subjective burden, role overload, and cortisol), perceived benefits, subjective health, psychological well-being, and depression. The secondary outcomes are caregiver coping, and behavioral problems and functional impairment of the care-recipient. Outcome measures are obtained at baseline, post-treatment (2 months), and 6, 12, 18 and 30 months. Discussion The emphasis on benefits, rather than losses and difficulties, provides a new dimension to the way interventions for caregivers can be conceptualized and delivered. By focusing on the positive, caregivers may be empowered to sustain caregiving efforts in the long term despite the day-to-day challenges. The two parallel trials will provide an assessment of whether the effectiveness of the intervention depends on the mode of

A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania Major Infection

DTIC Science & Technology

2010-01-01

A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania major...United States of America Abstract Background: Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan...with other species of Leishmania , or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two

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

PubMed Central

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

2017-01-01

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

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)

PubMed Central

Briel, Matthias; Lane, Melanie; Montori, Victor M; Bassler, Dirk; Glasziou, Paul; Malaga, German; Akl, Elie A; Ferreira-Gonzalez, Ignacio; Alonso-Coello, Pablo; Urrutia, Gerard; Kunz, Regina; Culebro, Carolina Ruiz; da Silva, Suzana Alves; Flynn, David N; Elamin, Mohamed B; Strahm, Brigitte; Murad, M Hassan; Djulbegovic, Benjamin; Adhikari, Neill KJ; Mills, Edward J; Gwadry-Sridhar, Femida; Kirpalani, Haresh; Soares, Heloisa P; Elnour, Nisrin O Abu; You, John J; Karanicolas, Paul J; Bucher, Heiner C; Lampropulos, Julianna F; Nordmann, Alain J; Burns, Karen EA; Mulla, Sohail M; Raatz, Heike; Sood, Amit; Kaur, Jagdeep; Bankhead, Clare R; Mullan, Rebecca J; Nerenberg, Kara A; Vandvik, Per Olav; Coto-Yglesias, Fernando; Schünemann, Holger; Tuche, Fabio; Chrispim, Pedro Paulo M; Cook, Deborah J; Lutz, Kristina; Ribic, Christine M; Vale, Noah; Erwin, Patricia J; Perera, Rafael; Zhou, Qi; Heels-Ansdell, Diane; Ramsay, Tim; Walter, Stephen D; Guyatt, Gordon H

2009-01-01

Background Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation. Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed

Increasing response rates to follow-up questionnaires in health intervention research: Randomized controlled trial of a gift card prize incentive.

PubMed

Morgan, Amy J; Rapee, Ronald M; Bayer, Jordana K

2017-08-01

Background/aims Achieving a high response rate to follow-up questionnaires in randomized controlled trials of interventions is important for study validity. Few studies have tested the value of incentives in increasing response rates to online questionnaires in clinical trials of health interventions. This study evaluated the effect of a gift card prize-draw incentive on response rates to follow-up questionnaires within a trial of an online health intervention. Method The study was embedded in a host randomized controlled trial of an online parenting program for child anxiety. A total of 433 participants were randomly allocated to one of two groups: (1) being informed that they would enter a gift card prize-draw if they completed the final study questionnaire (24-week follow-up) and (2) not informed about the prize-draw. All participants had a 1 in 20 chance of winning an AUD50 gift card after they completed the online questionnaire. Results The odds of the informed group completing the follow-up questionnaire were significantly higher than the uninformed group, (79.6% vs 68.5%, odds ratio = 1.79, 95% confidence interval = 1.15-2.79). This response rate increase of 11.1% (95% confidence interval = 2.8-19.1) occurred in both intervention and control groups in the host randomized controlled trial. The incentive was also effective in increasing questionnaire commencement (84.6% vs 75.9%, odds ratio = 1.74, 95% confidence interval = 1.07-2.84) and reducing the delay in completing the questionnaire (19.9 vs 22.6 days, hazard ratio = 1.34, 95% confidence interval = 1.07-1.67). Conclusion This study adds to evidence for the effectiveness of incentives to increase response rates to follow-up questionnaires in health intervention trials.

Patient Satisfaction with Different Interpreting Methods: A Randomized Controlled Trial

PubMed Central

Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C.; Changrani, Jyotsna

2007-01-01

Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. Methods 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. Results 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (β 0.10, 95% CI 0.02–0.18, scale 0–1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. Conclusions While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged

EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines. In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet. Methods/Design This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge. Discussion Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome

The NordICC Study: Rationale and design of a randomized trial on colonoscopy screening for colorectal cancer

PubMed Central

F.Kaminski, Michal; Bretthauer, Michael; Zauber, Ann G.; Kuipers, Ernst J.; Adami, Hans-Olov; van Ballegooijen, Marjolein; Regula, Jaroslaw; van Leerdam, Monique; Stefansson, Tryggvi; Påhlman, Lars; Dekker, Evelien; Hernán, Miguel A.; Garborg, Kjetil; Hoff, Geir

2017-01-01

Background While colonoscopy screening is widely used in several European countries and the United States, no randomised trials exist to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on CRC incidence and mortality. This paper describes the rationale and design of the NordICC trial. Material and methods Men and women age 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. Results The primary endpoints of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow up. We hypothesize a 50% CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50% compliance, yielding a 25% mortality reduction among those invited to screening. For 90% power and a two-sided alpha level of 0.05, using a 2:1 randomisation, 45,600 individuals will be randomised to control, and 22,800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10 years follow-up. Conclusions The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population. PMID:22723185

Bayesian randomized clinical trials: From fixed to adaptive design.

PubMed

Yin, Guosheng; Lam, Chi Kin; Shi, Haolun

2017-08-01

Randomized controlled studies are the gold standard for phase III clinical trials. Using α-spending functions to control the overall type I error rate, group sequential methods are well established and have been dominating phase III studies. Bayesian randomized design, on the other hand, can be viewed as a complement instead of competitive approach to the frequentist methods. For the fixed Bayesian design, the hypothesis testing can be cast in the posterior probability or Bayes factor framework, which has a direct link to the frequentist type I error rate. Bayesian group sequential design relies upon Bayesian decision-theoretic approaches based on backward induction, which is often computationally intensive. Compared with the frequentist approaches, Bayesian methods have several advantages. The posterior predictive probability serves as a useful and convenient tool for trial monitoring, and can be updated at any time as the data accrue during the trial. The Bayesian decision-theoretic framework possesses a direct link to the decision making in the practical setting, and can be modeled more realistically to reflect the actual cost-benefit analysis during the drug development process. Other merits include the possibility of hierarchical modeling and the use of informative priors, which would lead to a more comprehensive utilization of information from both historical and longitudinal data. From fixed to adaptive design, we focus on Bayesian randomized controlled clinical trials and make extensive comparisons with frequentist counterparts through numerical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

A Cluster Randomized Trial of Tailored Breastfeeding Support for Women with Gestational Diabetes

PubMed Central

Bonuck, Karen; Adatorwovor, Reuben; Schwartz, Todd A.; Berry, Diane C.

2016-01-01

Abstract Background: Women with gestational diabetes mellitus (GDM) and their infants are at increased risk of developing metabolic disease; however, longer breastfeeding is associated with a reduction in these risks. We tested an intervention to increase breastfeeding duration among women with GDM. Materials and Methods: We conducted a cluster randomized trial to determine the efficacy of a breastfeeding education and support program for women with GDM. Women were enrolled between 22 and 36 weeks of pregnancy and cluster randomized to an experimental lifestyle intervention or wait-list control group. Breastfeeding duration and intensity were prespecified secondary outcomes of the trial. Duration of exclusive and any breastfeeding was assessed at 6 weeks and at 4, 7, and 10 months postpartum. We quantified differences in breastfeeding rates using Kaplan–Meier estimates, log-rank tests, and Cox regression models. Results: We enrolled 100 women, of whom 52% were African American, 31% non-Hispanic white, 11% Hispanic, 9% American Indian or Alaskan Native, 2% Asian, 2% other, and 4% more than one race. In models accounting for within-cluster correlation and adjusted for study site, breastfeeding intention, and African American race, women allocated to the intervention group were less likely to stop breastfeeding (adjusted hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.21–0.74) or to introduce formula (adjusted HR 0.50, 95% CI 0.34–0.72). Conclusion: Our results suggest that targeted breastfeeding education for women with GDM is feasible and efficacious. Clinical Trials Registration: http://clinicaltrials.gov/ct2/show/NCT01809431 PMID:27782758

Moving a Randomized Clinical Trial into an Observational Cohort

PubMed Central

Goodman, Phyllis J.; Hartline, Jo Ann; Tangen, Catherine M.; Crowley, John J.; Minasian, Lori M.; Klein, Eric A.; Cook, Elise D.; Darke, Amy K.; Arnold, Kathryn B.; Anderson, Karen; Yee, Monica; Meyskens, Frank L.; Baker, Laurence H.

2013-01-01

Background The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo. The independent Data and Safety Monitoring Committee recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. Purpose A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-up (CFU) study. Methods The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures

The effect of primary delivery of the anterior compared with the posterior shoulder on perineal trauma: a study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Approximately 85% of vaginal deliveries are accompanied by perineal trauma. The objective of this trial is to compare the incidence and degree of perineal trauma after primary delivery of the anterior compared with the posterior shoulder during vaginal birth. The hypothesis is that primary delivery of the posterior shoulder reduces the rate and degree of perineal trauma. Methods/design This is a single-centre, randomized controlled trial, with computer-generated randomization in a 1:1 allocation ratio. Women planning their first vaginal delivery (n = 650) are randomized to primary delivery of either the anterior or posterior shoulder. The primary outcome is any perineal trauma. Additional outcomes are the perineal injury subtypes, postpartum bleeding, umbilical artery pH, Apgar score at 5 minutes and any neonatal birth trauma. Perineal trauma is assessed by a midwife or doctor blinded to the method of shoulder delivery. All midwives are trained in the two methods of shoulder delivery and in the grading of perineal tears. The trial is being undertaken at a Danish community hospital with 1,600 yearly deliveries. Data will be analyzed according to the intention-to-treat principle. Recruitment started in January 2013 and the trial is planned to proceed for 24 months. Discussion Most delivery assistance techniques are based on tradition and heritage and lack objective evidence. This trial provides an example of how vaginal delivery techniques can be evaluated in a randomized controlled trial. The results of this trial will clarify the role that delivery of the shoulders has on perineal trauma and thereby provide knowledge to recommendations on birthing technique. Trial registration ClinicalTrials.gov: NCT01937546. PMID:25047001

Chinese herbal medicine for the treatment of recurrent miscarriage: a systematic review of randomized clinical trials

PubMed Central

2013-01-01

Background Traditional Chinese medicine has been widely used for the treatment of recurrent miscarriage in China and other Asian countries for long time. We conducted this review to systematically summarize the evidences of Chinese herbal medicine (CHM) for the prevention and treatment of recurrent miscarriage in randomized trials, and evaluate the effectiveness and safety of CHM compared with placebo or conventional medicine. Methods We searched studies in PubMed, ClinicalTrials, the Cochrane Library, CNKI, SinoMed and VIP databases until December, 2012. Randomized trials on CHM alone or in combination with conventional medicine for recurrent miscarriage compared with placebo or conventional medicine were included. We evaluated the methodological quality of each included trials using the Cochrane risk of bias tool. Results A total of 41 RCTs (3660 participants) were included. The majority of trials had a high or unclear risk of bias. CHM used alone or plus progesterone-based treatment showed superior effect over progesterone-based treatment in improving live birth rate and embryonic developmental state (measured by B ultrasound). However, there is substantial heterogeneity within each subgroup analysis (I2 ranging from 35% to 71%). CHM plus progesterone and hCG-based treatment was superior to progesterone and hCG-based treatment in improving the embryonic developmental state, but not live birth rate. No severe adverse events were reported in relation to CHM. Conclusions Some Chinese herbal medicines or in combination with progesterone-based treatment demonstrated potentially beneficial effect in improving live birth rate and embryonic developmental state for women with recurrent miscarriage. However, due to the substantial heterogeneity among the herbal interventions and limitations of methodological quality of the included trials, it is not possible to recommend any specific CHMs for recurrent miscarriage. Further rigorous clinical trials are warranted to

Randomized Trial of Thymectomy in Myasthenia Gravis

PubMed Central

Wolfe, G.I.; Kaminski, H.J.; Aban, I.B.; Minisman, G.; Kuo, H.-C.; Marx, A.; Ströbel, P.; Mazia, C.; Oger, J.; Cea, J.G.; Heckmann, J.M.; Evoli, A.; Nix, W.; Ciafaloni, E.; Antonini, G.; Witoonpanich, R.; King, J.O.; Beydoun, S.R.; Chalk, C.H.; Barboi, A.C.; Amato, A.A.; Shaibani, A.I.; Katirji, B.; Lecky, B.R.F.; Buckley, C.; Vincent, A.; Dias-Tosta, E.; Yoshikawa, H.; Waddington-Cruz, M.; Pulley, M.T.; Rivner, M.H.; Kostera-Pruszczyk, A.; Pascuzzi, R.M.; Jackson, C.E.; Ramos, G.S. Garcia; Verschuuren, J.J.G.M.; Massey, J.M.; Kissel, J.T.; Werneck, L.C.; Benatar, M.; Barohn, R.J.; Tandan, R.; Mozaffar, T.; Conwit, R.; Odenkirchen, J.; Sonett, J.R.; Jaretzki, A.; Newsom-Davis, J.; Cutter, G.R.

2016-01-01

BACKGROUND Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS Thymectomy improved

A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function

PubMed Central

2012-01-01

Background Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. Methods/Design This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. Discussion This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span. The study is IRB approved and the number is: PRO08080012 ClinicalTrials.gov Identifier: NCT01443455 PMID:22672287

Using a partially randomized patient preference study design to evaluate the therapeutic effect of acupuncture and cupping therapy for fibromyalgia: study protocol for a partially randomized controlled trial

PubMed Central

2014-01-01

Background Conducting randomized controlled trials on traditional Chinese non-drug therapies has been limited by factors such as patient preference to specific treatment modality. The aim of this study is to investigate the feasibility of applying a partially randomized patient preference (PRPP) trial model in evaluating the efficacy of two types of traditional Chinese medicine therapies, acupuncture and cupping, for fibromyalgia while accounting for patients’ preference of either therapeutic modality. Methods This protocol was approved by the Institutional Ethics Committee of affiliated Dongfang Hospital, Beijing University of Chinese Medicine (approval number: 2013052104-2). One hundred participants with fibromyalgia will be included in this study. Diagnosis of fibromyalgia will be based on the American College of Rheumatology criteria. Before treatment, participants will be interviewed for their preference toward acupuncture or cupping therapy. Fifty participants with no preference will be randomly assigned to one of the two groups and another 50 participants with strong preference to either acupuncture or cupping will receive what they choose. For acupuncture and cupping therapy, the main acupoints used will be tender points (Ashi). Treatment will be three times a week for 5 consecutive weeks with a follow-up period of 12 weeks. Outcome measures will be qualitative (patient expectation and satisfaction) and quantitative (pain intensity, quality of life, depression assessment). Trial registration number NCT01869712 (in clinicaltrials.gov, on 22nd May 2013). PMID:25012121

The use of propensity scores to assess the generalizability of results from randomized trials

PubMed Central

Stuart, Elizabeth A.; Cole, Stephen R.; Bradshaw, Catherine P.; Leaf, Philip J.

2014-01-01

Randomized trials remain the most accepted design for estimating the effects of interventions, but they do not necessarily answer a question of primary interest: Will the program be effective in a target population in which it may be implemented? In other words, are the results generalizable? There has been very little statistical research on how to assess the generalizability, or “external validity,” of randomized trials. We propose the use of propensity-score-based metrics to quantify the similarity of the participants in a randomized trial and a target population. In this setting the propensity score model predicts participation in the randomized trial, given a set of covariates. The resulting propensity scores are used first to quantify the difference between the trial participants and the target population, and then to match, subclassify, or weight the control group outcomes to the population, assessing how well the propensity score-adjusted outcomes track the outcomes actually observed in the population. These metrics can serve as a first step in assessing the generalizability of results from randomized trials to target populations. This paper lays out these ideas, discusses the assumptions underlying the approach, and illustrates the metrics using data on the evaluation of a schoolwide prevention program called Positive Behavioral Interventions and Supports. PMID:24926156

Treatment of Subacromial Impingement Syndrome: Platelet-Rich Plasma or Exercise Therapy? A Randomized Controlled Trial

PubMed Central

Nejati, Parisa; Ghahremaninia, Armita; Naderi, Farrokh; Gharibzadeh, Safoora; Mazaherinezhad, Ali

2017-01-01

Background: Subacromial impingement syndrome (SAIS) is the most common disorder of the shoulder. The evidence for the effectiveness of treatment options is inconclusive and limited. Therefore, there is a need for more evidence in this regard, particularly for long-term outcomes. Hypothesis: Platelet-rich plasma (PRP) would be an effective method in treating subacromial impingement. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a single-blinded randomized clinical trial with 1-, 3-, and 6-month follow-up. Sixty-two patients were randomly placed into 2 groups, receiving either PRP or exercise therapy. The outcome parameters were pain, shoulder range of motion (ROM), muscle force, functionality, and magnetic resonance imaging findings. Results: Both treatment options significantly reduced pain and increased shoulder ROM compared with baseline measurements. Both treatments also significantly improved functionality. However, the treatment choices were not significantly effective in improving muscle force. Trend analysis revealed that in the first and third months, exercise therapy was superior to PRP in pain, shoulder flexion and abduction, and functionality. However, in the sixth month, only shoulder abduction and total Western Ontario Rotator Cuff score were significantly different between the 2 groups. Conclusion: Both PRP injection and exercise therapy were effective in reducing pain and disability in patients with SAIS, with exercise therapy proving more effective. PMID:28567426

A randomized, controlled trial of oral propranolol in infantile hemangioma.

PubMed

Léauté-Labrèze, Christine; Hoeger, Peter; Mazereeuw-Hautier, Juliette; Guibaud, Laurent; Baselga, Eulalia; Posiunas, Gintas; Phillips, Roderic J; Caceres, Hector; Lopez Gutierrez, Juan Carlos; Ballona, Rosalia; Friedlander, Sheila Fallon; Powell, Julie; Perek, Danuta; Metz, Brandie; Barbarot, Sebastien; Maruani, Annabel; Szalai, Zsuzsanna Zsofia; Krol, Alfons; Boccara, Olivia; Foelster-Holst, Regina; Febrer Bosch, Maria Isabel; Su, John; Buckova, Hana; Torrelo, Antonio; Cambazard, Frederic; Grantzow, Rainer; Wargon, Orli; Wyrzykowski, Dariusz; Roessler, Jochen; Bernabeu-Wittel, Jose; Valencia, Adriana M; Przewratil, Przemyslaw; Glick, Sharon; Pope, Elena; Birchall, Nicholas; Benjamin, Latanya; Mancini, Anthony J; Vabres, Pierre; Souteyrand, Pierre; Frieden, Ilona J; Berul, Charles I; Mehta, Cyrus R; Prey, Sorilla; Boralevi, Franck; Morgan, Caroline C; Heritier, Stephane; Delarue, Alain; Voisard, Jean-Jacques

2015-02-19

Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by

Treating major depression with yoga: A prospective, randomized, controlled pilot trial

PubMed Central

Rivera, Renee; Cochran, Ashly; Tungol, Jose Gabriel; Fayazmanesh, Nima; Weinmann, Eva

2017-01-01

Background Conventional pharmacotherapies and psychotherapies for major depression are associated with limited adherence to care and relatively low remission rates. Yoga may offer an alternative treatment option, but rigorous studies are few. This randomized controlled trial with blinded outcome assessors examined an 8-week hatha yoga intervention as mono-therapy for mild-to-moderate major depression. Methods Investigators recruited 38 adults in San Francisco meeting criteria for major depression of mild-to-moderate severity, per structured psychiatric interview and scores of 14–28 on Beck Depression Inventory-II (BDI). At screening, individuals engaged in psychotherapy, antidepressant pharmacotherapy, herbal or nutraceutical mood therapies, or mind-body practices were excluded. Participants were 68% female, with mean age 43.4 years (SD = 14.8, range = 22–72), and mean BDI score 22.4 (SD = 4.5). Twenty participants were randomized to 90-minute hatha yoga practice groups twice weekly for 8 weeks. Eighteen participants were randomized to 90-minute attention control education groups twice weekly for 8 weeks. Certified yoga instructors delivered both interventions at a university clinic. Primary outcome was depression severity, measured by BDI scores every 2 weeks from baseline to 8 weeks. Secondary outcomes were self-efficacy and self-esteem, measured by scores on the General Self-Efficacy Scale (GSES) and Rosenberg Self-Esteem Scale (RSES) at baseline and at 8 weeks. Results In intent-to-treat analysis, yoga participants exhibited significantly greater 8-week decline in BDI scores than controls (p-value = 0.034). In sub-analyses of participants completing final 8-week measures, yoga participants were more likely to achieve remission, defined per final BDI score ≤ 9 (p-value = 0.018). Effect size of yoga in reducing BDI scores was large, per Cohen’s d = -0.96 [95%CI, -1.81 to -0.12]. Intervention groups did not differ significantly in 8-week change scores for

A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

PubMed Central

Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S.

2011-01-01

Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale–cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. PMID:21795660

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

The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

2016-01-01

Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

Improving practice in community-based settings: a randomized trial of supervision – study protocol

PubMed Central

2013-01-01

Background Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes ‘gold standard’ supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. Methods/Design The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. Discussion This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will

Randomized trials are frequently fragmented in multiple secondary publications.

PubMed

Ebrahim, Shanil; Montoya, Luis; Kamal El Din, Mostafa; Sohani, Zahra N; Agarwal, Arnav; Bance, Sheena; Saquib, Juliann; Saquib, Nazmus; Ioannidis, John P A

2016-11-01

To assess the frequency and features of secondary publications of randomized controlled trials (RCTs). For 191 RCTs published in high-impact journals in 2009, we searched for secondary publications coauthored by at least one same author of the primary trial publication. We evaluated the probability of having secondary publications, characteristics of the primary trial publication that predict having secondary publications, types of secondary analyses conducted, and statistical significance of those analyses. Of 191 primary trials, 88 (46%) had a total of 475 secondary publications by 2/2014. Eight trials had >10 (up to 51) secondary publications each. In multivariable modeling, the risk of having subsequent secondary publications increased 1.32-fold (95% CI 1.05-1.68) per 10-fold increase in sample size, and 1.71-fold (95% CI 1.19-2.45) in the presence of a design article. In a sample of 197 secondary publications examined in depth, 193 tested different hypotheses than the primary publication. Of the 193, 43 tested differences between subgroups, 85 assessed predictive factors associated with an outcome of interest, 118 evaluated different outcomes than the original article, 71 had differences in eligibility criteria, and 21 assessed different durations of follow-up; 176 (91%) presented at least one analysis with statistically significant results. Approximately half of randomized trials in high-impact journals have secondary publications published with a few trials followed by numerous secondary publications. Almost all of these publications report some statistically significant results. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral isoflavone supplementation on endometrial thickness: a meta-analysis of randomized placebo-controlled trials

PubMed Central

Liu, Jie; Yuan, Feixiang; Gao, Jian; Shan, Boer; Ren, Yulan; Wang, Huaying; Gao, Ying

2016-01-01

Background Isoflavone from soy and other plants modulate hormonal effects in women, and the hormone disorder might result in different caners including endometrial cancer. However, it's effect on the risk of endometrial cancer is still inconclusive. We aimed to assess the effects of isoflavone on endometrial thickness, a risk factor of endometrial cancer in peri- and post-menopausal women. Methods A meta-analysis of randomized controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endometrial thickness in peri- and post-menopausal women. Electronic searches were performed on the PubMed, Embase, the Cochrane Library, web of science, CINAHL, and WHO ICTRP to August 1st, 2015. Reviews and reference lists of relevant articles were also searched to identify more studies. Summary estimates of standard mean differences (SMD's) and 95%CIs were obtained with random-effects models. Heterogeneity was evaluated with meta-regression and stratified analyses. Results A total of 23 trials were included in the current analysis. The overall results did not show significant change of endometrial thickness after oral isoflavone supplementation (23 studies, 2167subjects; SMD:-0.05; 95%CI:-0.23, 0.13; P=0.60). Stratified analysis suggested that a daily dose of more than 54mg could decrease the endometrial thickness for 0.26mm (10 trials, 984subjects; SMD:-0.26; 95%CI:-0.45, −0.07; P=0.007). Furthermore, isoflavone supplementation significantly decrease the endometrial thickness for 0.23mm in North American studies (7 trials, 726 subjects; SMD:-0.23; 95%CI:-0.44, −0.01; P=0.04), but it suggested an increase for 0.23mm in Asian studies (3 trials, 224 subjects; SMD: 0.23; 95%CI:-0.04, 0.50; P=0.10). Conclusion Oral isoflavone supplementation might have different effects in different populations and at different daily doses. Multiple-centre, larger, and long-term trials are deserved to further evaluate its effect. PMID:26967050

The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

ERIC Educational Resources Information Center

Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

2015-01-01

In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

Leveraging contact network structure in the design of cluster randomized trials.

PubMed

Harling, Guy; Wang, Rui; Onnela, Jukka-Pekka; De Gruttola, Victor

2017-02-01

In settings like the Ebola epidemic, where proof-of-principle trials have provided evidence of efficacy but questions remain about the effectiveness of different possible modes of implementation, it may be useful to conduct trials that not only generate information about intervention effects but also themselves provide public health benefit. Cluster randomized trials are of particular value for infectious disease prevention research by virtue of their ability to capture both direct and indirect effects of intervention, the latter of which depends heavily on the nature of contact networks within and across clusters. By leveraging information about these networks-in particular the degree of connection across randomized units, which can be obtained at study baseline-we propose a novel class of connectivity-informed cluster trial designs that aim both to improve public health impact (speed of epidemic control) and to preserve the ability to detect intervention effects. We several designs for cluster randomized trials with staggered enrollment, in each of which the order of enrollment is based on the total number of ties (contacts) from individuals within a cluster to individuals in other clusters. Our designs can accommodate connectivity based either on the total number of external connections at baseline or on connections only to areas yet to receive the intervention. We further consider a "holdback" version of the designs in which control clusters are held back from re-randomization for some time interval. We investigate the performance of these designs in terms of epidemic control outcomes (time to end of epidemic and cumulative incidence) and power to detect intervention effect, by simulating vaccination trials during an SEIR-type epidemic outbreak using a network-structured agent-based model. We compare results to those of a traditional Stepped Wedge trial. In our simulation studies, connectivity-informed designs lead to a 20% reduction in cumulative incidence

Examination of Cognitive Function During Six Months of Calorie Restriction: Results of a Randomized Controlled Trial

PubMed Central

Martin, Corby K.; Anton, Stephen D.; Han, Hongmei; York-Crowe, Emily; Redman, Leanne M.; Ravussin, Eric; Williamson, Donald A.

2009-01-01

Background Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested. Methods Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined. Results No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance. Conclusions This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases. PMID:17518698

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2016-10-01

subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO...within the proposed time frame. 15. SUBJECT TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY...propose a randomized controlled trial to test that promise. There is compelling epidemiologic, in-vitro, and in-vivo, evidence of aspirin’s potential

A multiple imputation strategy for sequential multiple assignment randomized trials

PubMed Central

Shortreed, Susan M.; Laber, Eric; Stroup, T. Scott; Pineau, Joelle; Murphy, Susan A.

2014-01-01

Sequential multiple assignment randomized trials (SMARTs) are increasingly being used to inform clinical and intervention science. In a SMART, each patient is repeatedly randomized over time. Each randomization occurs at a critical decision point in the treatment course. These critical decision points often correspond to milestones in the disease process or other changes in a patient’s health status. Thus, the timing and number of randomizations may vary across patients and depend on evolving patient-specific information. This presents unique challenges when analyzing data from a SMART in the presence of missing data. This paper presents the first comprehensive discussion of missing data issues typical of SMART studies: we describe five specific challenges, and propose a flexible imputation strategy to facilitate valid statistical estimation and inference using incomplete data from a SMART. To illustrate these contributions, we consider data from the Clinical Antipsychotic Trial of Intervention and Effectiveness (CATIE), one of the most well-known SMARTs to date. PMID:24919867

High-intensity training enhances executive function in children in a randomized, placebo-controlled trial

PubMed Central

Moreau, David; Kirk, Ian J; Waldie, Karen E

2017-01-01

Background: Exercise-induced cognitive improvements have traditionally been observed following aerobic exercise interventions; that is, sustained sessions of moderate intensity. Here, we tested the effect of a 6 week high-intensity training (HIT) regimen on measures of cognitive control and working memory in a multicenter, randomized (1:1 allocation), placebo-controlled trial. Methods: 318 children aged 7-13 years were randomly assigned to a HIT or an active control group matched for enjoyment and motivation. In the primary analysis, we compared improvements on six cognitive tasks representing two cognitive constructs (N = 305). Secondary outcomes included genetic data and physiological measurements. Results: The 6-week HIT regimen resulted in improvements on measures of cognitive control [BFM = 3.38, g = 0.31 (0.09, 0.54)] and working memory [BFM = 5233.68, g = 0.54 (0.31, 0.77)], moderated by BDNF genotype, with met66 carriers showing larger gains post-exercise than val66 homozygotes. Conclusion: This study suggests a promising alternative to enhance cognition, via short and potent exercise regimens. Clinical Trial Registration: Protocol #015078, University of Auckland. Funding: Centre for Brain Research: David Moreau and Karen E Waldie (9133-3706255). DOI: http://dx.doi.org/10.7554/eLife.25062.001 PMID:28825973

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

PubMed

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

2014-01-01

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

Comparison of Time-to-First Event and Recurrent Event Methods in Randomized Clinical Trials.

PubMed

Claggett, Brian; Pocock, Stuart; Wei, L J; Pfeffer, Marc A; McMurray, John J V; Solomon, Scott D

2018-03-27

Background -Most Phase-3 trials feature time-to-first event endpoints for their primary and/or secondary analyses. In chronic diseases where a clinical event can occur more than once, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared to conventional "time-to-first" methods. Methods -To better characterize factors that influence statistical properties of recurrent-events and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active vs control therapy, with true patient-level risk reduction of 20% (i.e. RR=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied a) the degree of between-patient heterogeneity of risk and b) the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results -As the degree of between-patient heterogeneity of risk was increased, both time-to-first and recurrent-events methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-events analyses continued to estimate the true RR=0.80 as heterogeneity increased, while the Cox model produced estimates that were attenuated. The power of recurrent-events methods declined as the rate of study drug discontinuation post-event increased. Recurrent-events methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% following a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials in chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-events methods

Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized trial

PubMed Central

2014-01-01

Background Despite significant increases in global health investment and the availability of low-cost, efficacious interventions to prevent mother-to-child HIV transmission (pMTCT) in low- and middle-income countries with high HIV burden, the translation of scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. A five-step, facility-level systems analysis and improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT service provision by improving understanding of inefficiencies (step one: cascade analysis), guiding identification and prioritization of low-cost workflow modifications (step two: value stream mapping), and iteratively testing and redesigning these modifications (steps three through five). This protocol describes the SAIA intervention and methods to evaluate the intervention’s impact on reducing drop-offs along the pMTCT cascade. Methods This study employs a two-arm, longitudinal cluster randomized trial design. The unit of randomization is the health facility. A total of 90 facilities were identified in Côte d’Ivoire, Kenya and Mozambique (30 per country). A subset was randomly selected and assigned to intervention and comparison arms, stratified by country and service volume, resulting in 18 intervention and 18 comparison facilities across all three countries, with six intervention and six comparison facilities per country. The SAIA intervention will be implemented for six months in the 18 intervention facilities. Primary trial outcomes are designed to assess improvements in the pMTCT service cascade, and include the percentage of pregnant women being tested for HIV at the first antenatal care visit, the percentage of HIV-infected pregnant women receiving adequate prophylaxis or combination antiretroviral therapy in pregnancy, and the percentage of newborns exposed to HIV in pregnancy receiving an HIV diagnosis eight

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

Key Items to Get Right When Conducting a Randomized Controlled Trial in Education

ERIC Educational Resources Information Center

Coalition for Evidence-Based Policy, 2005

2005-01-01

This is a checklist of key items to get right when conducting a randomized controlled trial to evaluate an educational program or practice ("intervention"). It is intended as a practical resource for researchers and sponsors of research, describing items that are often critical to the success of a randomized controlled trial. A significant…

Asthma Self-Management Model: Randomized Controlled Trial

ERIC Educational Resources Information Center

Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

2016-01-01

Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

ADAPTIVE MATCHING IN RANDOMIZED TRIALS AND OBSERVATIONAL STUDIES

PubMed Central

van der Laan, Mark J.; Balzer, Laura B.; Petersen, Maya L.

2014-01-01

SUMMARY In many randomized and observational studies the allocation of treatment among a sample of n independent and identically distributed units is a function of the covariates of all sampled units. As a result, the treatment labels among the units are possibly dependent, complicating estimation and posing challenges for statistical inference. For example, cluster randomized trials frequently sample communities from some target population, construct matched pairs of communities from those included in the sample based on some metric of similarity in baseline community characteristics, and then randomly allocate a treatment and a control intervention within each matched pair. In this case, the observed data can neither be represented as the realization of n independent random variables, nor, contrary to current practice, as the realization of n/2 independent random variables (treating the matched pair as the independent sampling unit). In this paper we study estimation of the average causal effect of a treatment under experimental designs in which treatment allocation potentially depends on the pre-intervention covariates of all units included in the sample. We define efficient targeted minimum loss based estimators for this general design, present a theorem that establishes the desired asymptotic normality of these estimators and allows for asymptotically valid statistical inference, and discuss implementation of these estimators. We further investigate the relative asymptotic efficiency of this design compared with a design in which unit-specific treatment assignment depends only on the units’ covariates. Our findings have practical implications for the optimal design and analysis of pair matched cluster randomized trials, as well as for observational studies in which treatment decisions may depend on characteristics of the entire sample. PMID:25097298

Hospital Inpatient versus HOme-based rehabilitation after knee arthroplasty (The HIHO study): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Formal rehabilitation programs are often assumed to be required after total knee arthroplasty to optimize patient recovery. Inpatient rehabilitation is a costly rehabilitation option after total knee arthroplasty and, in Australia, is utilized most frequently for privately insured patients. With the exception of comparisons with domiciliary services, no randomized trial has compared inpatient rehabilitation to any outpatient based program. The Hospital Inpatient versus HOme (HIHO) study primarily aims to determine whether 10 days of post-acute inpatient rehabilitation followed by a hybrid home program provides superior recovery of functional mobility on the 6-minute walk test (6MWT) compared to a hybrid home program alone following total knee arthroplasty. Secondarily, the trial aims to determine whether inpatient rehabilitation yields superior recovery in patient-reported function. Methods/Design This is a two-arm parallel randomized controlled trial (RCT), with a third, non-randomized, observational group. One hundred and forty eligible, consenting participants who have undergone a primary total knee arthroplasty at a high-volume joint replacement center will be randomly allocated when cleared for discharge from acute care to either 10 days of inpatient rehabilitation followed by usual care (a 6-week hybrid home program) or to usual care. Seventy participants in each group (140 in total) will provide 80% power at a significance level of 5% to detect an increase in walking capacity from 400 m to 460 m between the Home and Inpatient groups, respectively, in the 6MWT at 6 months post-surgery, assuming a SD of 120 m and a drop-out rate of <10%. The outcome assessor will assess participants at 10, 26 and 52 weeks post-operatively, and will remain blind to group allocation for the duration of the study, as will the statistician. Participant preference for rehabilitation mode stated prior to randomization will be accounted for in the analysis together

Best (but oft-forgotten) practices: designing, analyzing, and reporting cluster randomized controlled trials.

PubMed

Brown, Andrew W; Li, Peng; Bohan Brown, Michelle M; Kaiser, Kathryn A; Keith, Scott W; Oakes, J Michael; Allison, David B

2015-08-01

Cluster randomized controlled trials (cRCTs; also known as group randomized trials and community-randomized trials) are multilevel experiments in which units that are randomly assigned to experimental conditions are sets of grouped individuals, whereas outcomes are recorded at the individual level. In human cRCTs, clusters that are randomly assigned are typically families, classrooms, schools, worksites, or counties. With growing interest in community-based, public health, and policy interventions to reduce obesity or improve nutrition, the use of cRCTs has increased. Errors in the design, analysis, and interpretation of cRCTs are unfortunately all too common. This situation seems to stem in part from investigator confusion about how the unit of randomization affects causal inferences and the statistical procedures required for the valid estimation and testing of effects. In this article, we provide a brief introduction and overview of the importance of cRCTs and highlight and explain important considerations for the design, analysis, and reporting of cRCTs by using published examples. © 2015 American Society for Nutrition.

Surgical Mask to Prevent Influenza Transmission in Households: A Cluster Randomized Trial

PubMed Central

Canini, Laetitia; Andréoletti, Laurent; Ferrari, Pascal; D'Angelo, Romina; Blanchon, Thierry; Lemaitre, Magali; Filleul, Laurent; Ferry, Jean-Pierre; Desmaizieres, Michel; Smadja, Serge; Valleron, Alain-Jacques; Carrat, Fabrice

2010-01-01

Background Facemasks and respirators have been stockpiled during pandemic preparedness. However, data on their effectiveness for limiting transmission are scarce. We evaluated the effectiveness of facemask use by index cases for limiting influenza transmission by large droplets produced during coughing in households. Methodology and Principal Findings A cluster randomized intervention trial was conducted in France during the 2008–2009 influenza season. Households were recruited during a medical visit of a household member with a positive rapid influenza A test and symptoms lasting less than 48 hours. Households were randomized either to the mask or control group for 7 days. In the intervention arm, the index case had to wear a surgical mask from the medical visit and for a period of 5 days. The trial was initially intended to include 372 households but was prematurely interrupted after the inclusion of 105 households (306 contacts) following the advice of an independent steering committee. We used generalized estimating equations to test the association between the intervention and the proportion of household contacts who developed an influenza-like illness during the 7 days following the inclusion. Influenza-like illness was reported in 24/148 (16.2%) of the contacts in the intervention arm and in 25/158 (15.8%) of the contacts in the control arm and the difference between arms was 0.40% (95%CI: −10% to 11%, P = 1.00). We observed a good adherence to the intervention. In various sensitivity analyses, we did not identify any trend in the results suggesting effectiveness of facemasks. Conclusion This study should be interpreted with caution since the lack of statistical power prevents us to draw formal conclusion regarding effectiveness of facemasks in the context of a seasonal epidemic. Trial Registration clinicaltrials.gov NCT00774774 PMID:21103330

Testing use of payers to facilitate evidence-based practice adoption: protocol for a cluster-randomized trial

PubMed Central

2013-01-01

Background More effective methods are needed to implement evidence-based findings into practice. The Advancing Recovery Framework offers a multi-level approach to evidence-based practice implementation by aligning purchasing and regulatory policies at the payer level with organizational change strategies at the organizational level. Methods The Advancing Recovery Buprenorphine Implementation Study is a cluster-randomized controlled trial designed to increase use of the evidence-based practice buprenorphine medication to treat opiate addiction. Ohio Alcohol, Drug Addiction, and Mental Health Services Boards (ADAMHS), who are payers, and their addiction treatment organizations were recruited for a trial to assess the effects of payer and treatment organization changes (using the Advancing Recovery Framework) versus treatment organization changes alone on the use of buprenorphine. A matched-pair randomization, based on county characteristics, was applied, resulting in seven county ADAMHS boards and twenty-five treatment organizations in each arm. Opioid dependent patients are nested within cluster (treatment organization), and treatment organization clusters are nested within ADAMHS county board. The primary outcome is the percentage of individuals with an opioid dependence diagnosis who use buprenorphine during the 24-month intervention period and the 12-month sustainability period. The trial is currently in the baseline data collection stage. Discussion Although addiction treatment providers are under increasing pressure to implement evidence-based practices that have been proven to improve patient outcomes, adoption of these practices lags, compared to other areas of healthcare. Reasons frequently cited for the slow adoption of EBPs in addiction treatment include, regulatory issues, staff, or client resistance and lack of resources. Yet the way addiction treatment is funded, the payer’s role—has not received a lot of attention in research on EBP adoption. This

A random walk model for evaluating clinical trials involving serial observations.

PubMed

Hopper, J L; Young, G P

1988-05-01

For clinical trials where the variable of interest is ordered and categorical (for example, disease severity, symptom scale), and where measurements are taken at intervals, it might be possible to achieve a greater discrimination between the efficacy of treatments by modelling each patient's progress as a stochastic process. The random walk is a simple, easily interpreted model that can be fitted by maximum likelihood using a maximization routine with inference based on standard likelihood theory. In general the model can allow for randomly censored data, incorporates measured prognostic factors, and inference is conditional on the (possibly non-random) allocation of patients. Tests of fit and of model assumptions are proposed, and application to two therapeutic trials of gastroenterological disorders are presented. The model gave measures of the rate of, and variability in, improvement for patients under different treatments. A small simulation study suggested that the model is more powerful than considering the difference between initial and final scores, even when applied to data generated by a mechanism other than the random walk model assumed in the analysis. It thus provides a useful additional statistical method for evaluating clinical trials.

Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized, Controlled Trials

PubMed Central

Sun, Zikai; Fu, Qiang; Cao, Longxing; Jin, Wen; Cheng, LingLing; Li, Zhiliang

2013-01-01

Background Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media. Study Design Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed. Results Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I2 = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics. Conclusion This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different

A randomized trial comparing digital and live lecture formats [ISRCTN40455708

PubMed Central

Solomon, David J; Ferenchick, Gary S; Laird-Fick, Heather S; Kavanaugh, Kevin

2004-01-01

Background Medical education is increasingly being conducted in community-based teaching sites at diverse locations, making it difficult to provide a consistent curriculum. We conducted a randomized trial to assess whether students who viewed digital lectures would perform as well on a measure of cognitive knowledge as students who viewed live lectures. Students' perceptions of the digital lecture format and their opinion as whether a digital lecture format could serve as an adequate replacement for live lectures was also assessed. Methods Students were randomized to either attend a lecture series at our main campus or view digital versions of the same lectures at community-based teaching sites. Both groups completed the same examination based on the lectures, and the group viewing the digital lectures completed a feedback form on the digital format. Results There were no differences in performance as measured by means or average rank. Despite technical problems, the students who viewed the digital lectures overwhelmingly felt the digital lectures could replace live lectures. Conclusions This study provides preliminary evidence digital lectures can be a viable alternative to live lectures as a means of delivering didactic presentations in a community-based setting. PMID:15569389

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

PubMed Central

Cao, Huijuan; Zhu, Chenjun; Liu, Jianping

2011-01-01

Background Wet cupping is a traditional Chinese medicine therapy commonly used in treating herpes zoster in China, and clinical studies have shown that wet cupping may have beneficial effect on herpes zoster compared with western medication. Methods We included randomized controlled trials on wet cupping for herpes zoster. We searched PubMed, the Cochrane Library (Issue 3, 2008), China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wan Fang Database. All searches ended in February 2009. Two authors extracted data and assessed the trials quality independently. RevMan 5.0.18 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). Results 8 RCTs involving 651 patients were included, and the methodological quality of trials was generally fair in terms of randomization, blinding and intention-to-treat analysis. Meta-analyses showed wet cupping was superior to medications regarding the number of cured patients (RR 2.49, 95%CI 1.91 to 3.24, p<0.00001), the number of patients with improved symptoms (RR 1.15, 95%CI 1.05 to 1.26, p=0.003), and reducing the incidence rate of postherpetic neuralgia (RR 0.06, 95%CI 0.02 to 0.25, p=0.0001). Wet cupping plus medications was significantly better than medications alone on number of cured patients (RR 1.93, 95%CI 1.23 to 3.04, p=0.005), but no difference in symptom improvement (RR 1.00, 95%CI 0.92 to 1.08, p=0.98). There were no serious adverse effects with related to wet cupping therapy in the included trials. Conclusions Wet cupping appears to be effective in treatment of herpes zoster. However, further large, rigorous designed trials are warranted. PMID:21280462

A Data Management System Integrating Web-based Training and Randomized Trials: Requirements, Experiences and Recommendations.

PubMed

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance of web-course-trained participants (intervention group) and printed-manual-trained participants (comparison group) to determine the effectiveness of the web-course in teaching CBT skills. A single DMS was needed to support all aspects of the study: web-course delivery and management, as well as randomized trial management. The authors briefly reviewed several other systems that were described as built either to handle randomized trials or to deliver and evaluate web-based training. However it was clear that these systems fell short of meeting our needs for simultaneous, coordinated management of the web-course and the randomized trial. New England Research Institute's (NERI) proprietary Advanced Data Entry and Protocol Tracking (ADEPT) system was coupled with the web-programmed course and customized for our purposes. This article highlights the requirements for a DMS that operates at the intersection of web-based course management systems and randomized clinical trial systems, and the extent to which the coupled, customized ADEPT satisfied those requirements. Recommendations are included for institutions and individuals considering conducting randomized trials and web-based training programs, and seeking a DMS that can meet similar requirements.

Sample Size Calculations for Micro-randomized Trials in mHealth

PubMed Central

Liao, Peng; Klasnja, Predrag; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

The use and development of mobile interventions are experiencing rapid growth. In “just-in-time” mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions “in the moment,” and thus have a proximal, near future impact. Currently the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we propose a “micro-randomized” trial design for this purpose. In a micro-randomized trial, treatments are sequentially randomized throughout the conduct of the study, with the result that each participant may be randomized at the 100s or 1000s of occasions at which a treatment might be provided. Further, we develop a test statistic for assessing the proximal effect of a treatment as well as an associated sample size calculator. We conduct simulation evaluations of the sample size calculator in various settings. Rules of thumb that might be used in designing a micro-randomized trial are discussed. This work is motivated by our collaboration on the HeartSteps mobile application designed to increase physical activity. PMID:26707831

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

PubMed

Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

2016-11-30

Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant

China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China

PubMed Central

Gao, Peng; Zhao, Zhenwei; Wang, Daming; Wu, Jian; Cai, Yiling; Li, Tianxiao; Wu, Wei; Shi, Huaizhang; He, Weiwen; Zhu, Fengshui; Ling, Feng

2015-01-01

Background Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. Methods The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%–99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. Conclusion In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The

Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram

PubMed Central

Lavretsky, H.; Siddarth, P.; Irwin, M. R.

2009-01-01

Background This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blind trial. Methods Forty family caregivers (43–91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer’s disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient’s cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale (HDRS) scores at baseline ranged between 10–28. The groups were stratified by the diagnosis of major and minor depression. Results Most outcomes favored escitalopram over placebo. The severity of depression improved and the remission rate was greater with the drug compared to placebo. Measures of anxiety, resilience, burden and distress improved on escitalopram compared to placebo. Discussion Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample. PMID:20104071

Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

PubMed

NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

2017-08-01

Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

Urn models for response-adaptive randomized designs: a simulation study based on a non-adaptive randomized trial.

PubMed

Ghiglietti, Andrea; Scarale, Maria Giovanna; Miceli, Rosalba; Ieva, Francesca; Mariani, Luigi; Gavazzi, Cecilia; Paganoni, Anna Maria; Edefonti, Valeria

2018-03-22

Recently, response-adaptive designs have been proposed in randomized clinical trials to achieve ethical and/or cost advantages by using sequential accrual information collected during the trial to dynamically update the probabilities of treatment assignments. In this context, urn models-where the probability to assign patients to treatments is interpreted as the proportion of balls of different colors available in a virtual urn-have been used as response-adaptive randomization rules. We propose the use of Randomly Reinforced Urn (RRU) models in a simulation study based on a published randomized clinical trial on the efficacy of home enteral nutrition in cancer patients after major gastrointestinal surgery. We compare results with the RRU design with those previously published with the non-adaptive approach. We also provide a code written with the R software to implement the RRU design in practice. In detail, we simulate 10,000 trials based on the RRU model in three set-ups of different total sample sizes. We report information on the number of patients allocated to the inferior treatment and on the empirical power of the t-test for the treatment coefficient in the ANOVA model. We carry out a sensitivity analysis to assess the effect of different urn compositions. For each sample size, in approximately 75% of the simulation runs, the number of patients allocated to the inferior treatment by the RRU design is lower, as compared to the non-adaptive design. The empirical power of the t-test for the treatment effect is similar in the two designs.

Saving and Empowering Young Lives in Europe (SEYLE): a randomized controlled trial

PubMed Central

2010-01-01

Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior, and, in most of those studies, the target populations were primarily adults, whereas few focused on adolescents. Essentially, there have been no randomized controlled studies comparing the efficacy, cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools. There is also a lack of information on whether suicide-preventive interventions can, in addition to preventing suicide, reduce risk behaviors and promote healthier ones as well as improve young people's mental health. The aim of the SEYLE project, which is funded by the European Union under the Seventh Framework Health Program, is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological database; testing, in a randomized controlled trial, three different suicide-preventive interventions; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors. Methods and design The study comprises 11,000 adolescents emitted from randomized schools in 11 European countries: Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the scientific coordinating center. Each country performs three active interventions and one minimal intervention as a control group. The active interventions include gatekeeper training (QPR), awareness training on mental health promotion for adolescents, and screening for at-risk adolescents by health professionals. Structured questionnaires are utilized at baseline, 3- and 12-month follow-ups in order to assess changes. Discussion Although it has been reported that suicide

Implementation of a Manualized Communication Intervention for School-Aged Children with Pragmatic and Social Communication Needs in a Randomized Controlled Trial: The Social Communication Intervention Project

ERIC Educational Resources Information Center

Adams, Catherine; Lockton, Elaine; Gaile, Jacqueline; Earl, Gillian; Freed, Jenny

2012-01-01

Background: Speech-language interventions are often complex in nature, involving multiple observations, variable outcomes and individualization in treatment delivery. The accepted procedure associated with randomized controlled trials (RCT) of such complex interventions is to develop and implement a manual of intervention in order that reliable…

Antibiotics for human toxoplasmosis: a systematic review of randomized trials

PubMed Central

Rajapakse, Senaka; Chrishan Shivanthan, Mitrakrishnan; Samaranayake, Nilakshi; Rodrigo, Chaturaka; Deepika Fernando, Sumadhya

2013-01-01

The efficacy of different treatment regimens in clinical syndromes of toxoplasmosis were assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE, EMBASE, and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on the clinical entity of toxoplasmosis. Risk of bias was evaluated and quality of evidence was graded. Fourteen randomized trials were included of which one was a non-comparative study. One well-designed trial showed that trimethoprim-sulphamethoxazole was more effective than placebo for clinical recovery of toxoplasmic lymphadenopathy in immunocompetent hosts. For toxoplasmic encephalopathy, efficacy of pyrimethamine+sulphadiazine and trimethoprim+sulphamethoxazole were similar, whereas pyrimethamine+sulphadiazine versus pyrimathamine+clindamycin showed no difference, irrespective of the outcome. Intravitreal clindamycin+dexamethasone and conventional treatment with oral pyrimethamine+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with pyrimethamine+sulphadiazine. Most trials for encephalitis and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. Pyrimethamine+sulphadiazine is an effective therapy for treatment of toxoplasmic encephalitis; trimethoprim+sulphamethoxazole and pyrimethamine+clindamycin are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis. Overall, trial evidence for the efficacy of these drugs for toxoplasmosis is poor, and further well-designed trials are needed. PMID:23816507

Randomized Trial of Interventions to Improve Childhood Asthma in Homes with Wood-burning Stoves

PubMed Central

Semmens, Erin O.; Smith, Paul; Harrar, Solomon W.; Montrose, Luke; Weiler, Emily; McNamara, Marcy; Ward, Tony J.

2017-01-01

Background: Household air pollution due to biomass combustion for residential heating adversely affects vulnerable populations. Randomized controlled trials to improve indoor air quality in homes of children with asthma are limited, and no such studies have been conducted in homes using wood for heating. Objectives: Our aims were to test the hypothesis that household-level interventions, specifically improved-technology wood-burning appliances or air-filtration devices, would improve health measures, in particular Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores, relative to placebo, among children living with asthma in homes with wood-burning stoves. Methods: A three-arm placebo-controlled randomized trial was conducted in homes with wood-burning stoves among children with asthma. Multiple preintervention and postintervention data included PAQLQ (primary outcome), peak expiratory flow (PEF) monitoring, diurnal peak flow variability (dPFV, an indicator of airway hyperreactivity) and indoor particulate matter (PM) PM2.5. Results: Relative to placebo, neither the air filter nor the woodstove intervention showed improvement in quality-of-life measures. Among the secondary outcomes, dPFV showed a 4.1 percentage point decrease in variability [95% confidence interval (CI)=−7.8 to −0.4] for air-filtration use in comparison with placebo. The air-filter intervention showed a 67% (95% CI: 50% to 77%) reduction in indoor PM2.5, but no change was observed with the improved-technology woodstove intervention. Conclusions: Among children with asthma and chronic exposure to woodsmoke, an air-filter intervention that improved indoor air quality did not affect quality-of-life measures. Intent-to-treat analysis did show an improvement in the secondary measure of dPFV. Trial registration: ClincialTrials.gov NCT00807183. https://doi.org/10.1289/EHP849 PMID:28935614

10-year trend in quantity and quality of pediatric randomized controlled trials published in mainland China: 2002–2011

PubMed Central

2013-01-01

Background Quality assessment of pediatric randomized controlled trials (RCTs) in China is limited. The aim of this study was to evaluate the quantitative trends and quality indicators of RCTs published in mainland China over a recent 10-year period. Methods We individually searched all 17 available pediatric journals published in China from January 1, 2002 to December 30, 2011 to identify RCTs of drug treatment in participants under the age of 18 years. The quality was evaluated according to the Cochrane quality assessment protocol. Results Of 1287 journal issues containing 44398 articles, a total of 2.4% (1077/44398) articles were included in the analysis. The proportion of RCTs increased from 0.28% in 2002 to 0.32% in 2011. Individual sample sizes ranged from 10 to 905 participants (median 81 participants); 2.3% of the RCTs were multiple center trials; 63.9% evaluated Western medicine, 32.5% evaluated traditional Chinese medicine; 15% used an adequate method of random sequence generation; and 10.4% used a quasi-random method for randomization. Only 1% of the RCTs reported adequate allocation concealment and 0.6% reported the method of blinding. The follow-up period was from 7 days to 96 months, with a median of 7.5 months. There was incomplete outcome data reported in 8.3%, of which 4.5% (4/89) used intention-to-treat analysis. Only 0.4% of the included trials used adequate random sequence allocation, concealment and blinding. The articles published from 2007 to 2011 revealed an improvement in the randomization method compared with articles published from 2002 to 2006 (from 2.7% to 23.6%, p = 0.000). Conclusions In mainland China, the quantity of RCTs did not increase in the pediatric population, and the general quality was relatively poor. Quality improvements were suboptimal in the later 5 years. PMID:23914882

Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

PubMed Central

2011-01-01

Background Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. Methods A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). Results There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. Conclusions Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means. PMID:21299861

A Randomized Pilot Trial of Remote Ischemic Preconditioning in Heart Failure with Reduced Ejection Fraction

PubMed Central

McDonald, Michael A.; Braga, Juarez R.; Li, Jing; Manlhiot, Cedric; Ross, Heather J.; Redington, Andrew N.

2014-01-01

Background Remote ischemic preconditioning (RIPC) induced by transient limb ischemia confers multi-organ protection and improves exercise performance in the setting of tissue hypoxia. We aimed to evaluate the effect of RIPC on exercise capacity in heart failure patients. Methods We performed a randomized crossover trial of RIPC (4×5-minutes limb ischemia) compared to sham control in heart failure patients undergoing exercise testing. Patients were randomly allocated to either RIPC or sham prior to exercise, then crossed over and completed the alternate intervention with repeat testing. The primary outcome was peak VO2, RIPC versus sham. A mechanistic substudy was performed using dialysate from study patient blood samples obtained after sham and RIPC. This dialysate was used to test for a protective effect of RIPC in a mouse heart Langendorff model of infarction. Mouse heart infarct size with RIPC or sham dialysate exposure was also compared with historical control data. Results Twenty patients completed the study. RIPC was not associated with improvements in peak VO2 (15.6+/−4.2 vs 15.3+/−4.6 mL/kg/min; p = 0.53, sham and RIPC, respectively). In our Langendorff sub-study, infarct size was similar between RIPC and sham dialysate groups from our study patients, but was smaller than expected compared to healthy controls (29.0%, 27.9% [sham, RIPC] vs 51.2% [controls]. We observed less preconditioning among the subgroup of patients with increased exercise performance following RIPC (p<0.04). Conclusion In this pilot study of RIPC in heart failure patients, RIPC was not associated with improvements in exercise capacity overall. However, the degree of effect of RIPC may be inversely related to the degree of baseline preconditioning. These data provide the basis for a larger randomized trial to test the potential benefits of RIPC in patients with heart failure. Trial Registration ClinicalTrials.gov +++++NCT01128790 PMID:25181050

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

Estimation of treatment efficacy with complier average causal effects (CACE) in a randomized stepped wedge trial.

PubMed

Gruber, Joshua S; Arnold, Benjamin F; Reygadas, Fermin; Hubbard, Alan E; Colford, John M

2014-05-01

Complier average causal effects (CACE) estimate the impact of an intervention among treatment compliers in randomized trials. Methods used to estimate CACE have been outlined for parallel-arm trials (e.g., using an instrumental variables (IV) estimator) but not for other randomized study designs. Here, we propose a method for estimating CACE in randomized stepped wedge trials, where experimental units cross over from control conditions to intervention conditions in a randomized sequence. We illustrate the approach with a cluster-randomized drinking water trial conducted in rural Mexico from 2009 to 2011. Additionally, we evaluated the plausibility of assumptions required to estimate CACE using the IV approach, which are testable in stepped wedge trials but not in parallel-arm trials. We observed small increases in the magnitude of CACE risk differences compared with intention-to-treat estimates for drinking water contamination (risk difference (RD) = -22% (95% confidence interval (CI): -33, -11) vs. RD = -19% (95% CI: -26, -12)) and diarrhea (RD = -0.8% (95% CI: -2.1, 0.4) vs. RD = -0.1% (95% CI: -1.1, 0.9)). Assumptions required for IV analysis were probably violated. Stepped wedge trials allow investigators to estimate CACE with an approach that avoids the stronger assumptions required for CACE estimation in parallel-arm trials. Inclusion of CACE estimates in stepped wedge trials with imperfect compliance could enhance reporting and interpretation of the results of such trials.

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial.

PubMed

Demaerschalk, Bart M; Brown, Robert D; Roubin, Gary S; Howard, Virginia J; Cesko, Eldina; Barrett, Kevin M; Longbottom, Mary E; Voeks, Jenifer H; Chaturvedi, Seemant; Brott, Thomas G; Lal, Brajesh K; Meschia, James F; Howard, George

2017-09-01

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217. © 2017

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

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

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

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

Effect of Oral Carbohydrate Intake on Labor Progress: Randomized Controlled Trial

PubMed Central

Rahmani, R; Khakbazan, Z; Yavari, P; Granmayeh, M; Yavari, L

2012-01-01

Background Lack of information regarding biochemical changes in women during labor and its outcomes on maternal and neonatal health still is an unanswered question. This study aims to explore the effectiveness of oral carbohydrate intake during labor on the duration of the active phase and other maternal and neonatal outcomes. Methods: A parallel prospective randomized controlled trial, conducted at the University Affiliated Teaching Hospital in Gonabad. Totally, 190 women were randomly assigned to an intervention (N=87) or control (N=90) group. Inclusion criteria were low-risk women with singleton cephalic presentation; and cervical dilatation 3–4 cm. Randomization was used by random number generator on every day. Odd numbers was used for intervention and even numbers for control group. Intervention was based on the preferences between: 3 medium dates plus 110 ml water; 3 dates plus 110 ml light tea without sugar; or 110 ml orange juice. The protocol is only run once but women ate and drank gradually before second stage of labor. Control group were fasted as routine practice. Neither participants nor care givers or staff could be blinded to group allocation. Differences between duration of the active phase of labor were assessed as primary outcome measure. Results: There was significant difference in the length of second stage of labor (P <.05). The effect size for this variable was 0.48. There were no significant differences in other maternal and neonatal outcomes. Conclusions: Oral intake of carbohydrate was an effective method for shortening the duration of second stage of labor in low-risk women. PMID:23304677

Confidence intervals for a difference between lognormal means in cluster randomization trials.

PubMed

Poirier, Julia; Zou, G Y; Koval, John

2017-04-01

Cluster randomization trials, in which intact social units are randomized to different interventions, have become popular in the last 25 years. Outcomes from these trials in many cases are positively skewed, following approximately lognormal distributions. When inference is focused on the difference between treatment arm arithmetic means, existent confidence interval procedures either make restricting assumptions or are complex to implement. We approach this problem by assuming log-transformed outcomes from each treatment arm follow a one-way random effects model. The treatment arm means are functions of multiple parameters for which separate confidence intervals are readily available, suggesting that the method of variance estimates recovery may be applied to obtain closed-form confidence intervals. A simulation study showed that this simple approach performs well in small sample sizes in terms of empirical coverage, relatively balanced tail errors, and interval widths as compared to existing methods. The methods are illustrated using data arising from a cluster randomization trial investigating a critical pathway for the treatment of community acquired pneumonia.

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

ERIC Educational Resources Information Center

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

2017-01-01

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

Levofloxacin-Based First-Line Therapy versus Standard First-Line Therapy for Helicobacter pylori Eradication: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Peedikayil, Musthafa Chalikandy; AlSohaibani, Fahad Ibrahim; Alkhenizan, Abdullah Hamad

2014-01-01

Background First-line levofloxacin-based treatments eradicate Helicobacter pylori with varying success. We examined the efficacy and safety of first-line levofloxacin-based treatment in comparison to standard first-line therapy for H pylori eradication. Materials and Methods We searched literature databases from Medline, EMBASE, and the Cochrane Register of Randomized Controlled Trials through March 2013 for randomized controlled trials comparing first-line levofloxacin and standard therapy. We included randomized controlled trials conducted only on naïve H pylori infected patients in adults. A systematic review was conducted. Meta-analysis was performed with Review Manager 5.2. Treatment effect was determined by relative risk with a random or fixed model by the Mantel-Haenszel method. Results Seven trials were identified with 888 patients receiving 7 days of first-line levofloxacin and 894 treated with standard therapy (Amoxicillin, Clarithromycin and proton pump inhibitor) for 7 days. The overall crude eradication rate in the Levofloxacin group was 79.05% versus 81.4% in the standard group (risk ratio 0.97; 95% CI; 0.93, 1.02). The overall dropout was 46 (5.2%) in the levofloxacin group and 52 (5.8%) for standard therapy. The dizziness was more common among group who took Levofloxacin based treatment and taste disturbance was more common among group who took standard therapy. Meta-analysis of overall adverse events were similar between the two groups with a relative risk of 1.06 (95% CI 0.72, 1.57). Conclusion Helicobacter pylori eradication with 7 days of Levofloxacin-based first line therapy was safe and equal compared to 7 days of standard first-line therapy. PMID:24465624

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

The role of gender in a smoking cessation intervention: a cluster randomized clinical trial

PubMed Central

2011-01-01

Background The prevalence of smoking in Spain is high in both men and women. The aim of our study was to evaluate the role of gender in the effectiveness of a specific smoking cessation intervention conducted in Spain. Methods This study was a secondary analysis of a cluster randomized clinical trial in which the randomization unit was the Basic Care Unit (family physician and nurse who care for the same group of patients). The intervention consisted of a six-month period of implementing the recommendations of a Clinical Practice Guideline. A total of 2,937 current smokers at 82 Primary Care Centers in 13 different regions of Spain were included (2003-2005). The success rate was measured by a six-month continued abstinence rate at the one-year follow-up. A logistic mixed-effects regression model, taking Basic Care Units as random-effect parameter, was performed in order to analyze gender as a predictor of smoking cessation. Results At the one-year follow-up, the six-month continuous abstinence quit rate was 9.4% in men and 8.5% in women (p = 0.400). The logistic mixed-effects regression model showed that women did not have a higher odds of being an ex-smoker than men after the analysis was adjusted for confounders (OR adjusted = 0.9, 95% CI = 0.7-1.2). Conclusions Gender does not appear to be a predictor of smoking cessation at the one-year follow-up in individuals presenting at Primary Care Centers. ClinicalTrials.gov Identifier NCT00125905. PMID:21605389

Lumbar Imaging with Reporting of Epidemiology (LIRE)- Protocol for a Pragmatic Cluster Randomized Trial

PubMed Central

Jarvik, Jeffrey G.; Comstock, Bryan A.; James, Kathryn T.; Avins, Andrew L.; Bresnahan, Brian W.; Deyo, Richard A.; Luetmer, Patrick H.; Friedly, Janna L.; Meier, Eric N.; Cherkin, Daniel C.; Gold, Laura S.; Rundell, Sean D.; Halabi, Safwan S.; Kallmes, David F.; Tan, Katherine W.; Turner, Judith A.; Kessler, Larry G.; Lavallee, Danielle C.; Stephens, Kari A.; Heagerty, Patrick J.

2015-01-01

Background Diagnostic imaging is often the first step in evaluating patients with back pain and likely functions as a “gateway” to a subsequent cascade of interventions. However, lumbar spine imaging frequently reveals incidental findings among normal, pain-free individuals suggesting that treatment of these “abnormalities” may not be warranted. Our prior work suggested that inserting the prevalence of imaging findings in patients without back pain into spine imaging reports may reduce subsequent interventions. We are now conducting a pragmatic cluster randomized clinical trial to test the hypothesis that inserting this prevalence data into lumbar spine imaging reports for studies ordered by primary care providers will reduce subsequent spine-related interventions. Methods/Design We are using a stepped wedge design that sequentially randomizes 100 primary care clinics at four health systems to receive either standard lumbar spine imaging reports, or reports containing prevalence data for common imaging findings in patients without back pain. We capture all outcomes passively through the electronic medical record. Our primary outcome is spine-related intervention intensity based on Relative Value Units (RVUs) during the following year. Secondary outcomes include subsequent prescriptions for opioid analgesics and cross-sectional lumbar spine re-imaging. Discussion If our study shows that adding prevalence data to spine imaging reports decreases subsequent back-related RVUs, this intervention could be easily generalized and applied to other kinds of testing, as well as other conditions where incidental findings may be common. Our study also serves as a model for cluster randomized trials that are minimal risk and highly pragmatic. PMID:26493088

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

PubMed

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles

Assessments of the quality of randomized controlled trials published in International Journal of Urology from 1994 to 2011.

PubMed

Cho, Hee Ju; Chung, Jae Hoon; Jo, Jung Ki; Kang, Dong Hyuk; Cho, Jeong Man; Yoo, Tag Keun; Lee, Seung Wook

2013-12-01

Randomized controlled trials are one of the most reliable resources for assessing the effectiveness and safety of medical treatments. Low quality randomized controlled trials carry a large bias that can ultimately impair the reliability of their conclusions. The present study aimed to evaluate the quality of randomized controlled trials published in International Journal of Urology by using multiple quality assessment tools. Randomized controlled trials articles published in International Journal of Urology were found using the PubMed MEDLINE database, and qualitative analysis was carried out with three distinct assessment tools: the Jadad scale, the van Tulder scale and the Cochrane Collaboration Risk of Bias Tool. The quality of randomized controlled trials was analyzed by publication year, type of subjects, intervention, presence of funding and whether an institutional review board reviewed the study. A total of 68 randomized controlled trial articles were published among a total of 1399 original articles in International Journal of Urology. Among these randomized controlled trials, 10 (2.70%) were from 1994 to 1999, 23 (4.10%) were from 2000 to 2005 and 35 (4.00%) were from 2006 to 2011 (P = 0.494). On the assessment with the Jadad and van Tulder scale, the numbers and percentage of high quality randomized controlled trials increased over time. The studies that had institutional review board reviews, funding resources or that were carried out in multiple institutions had an increased percentage of high quality articles. The numbers and percentage of high-quality randomized controlled trials published in International Journal of Urology have increased over time. Furthermore, randomized controlled trials with funding resources, institutional review board reviews or carried out in multiple institutions have been found to be of higher quality compared with others not presenting these features. © 2013 The Japanese Urological Association.

A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain

PubMed Central

Watson, C Peter N; Gilron, Ian; Sawynok, Jana

2010-01-01

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID:20577657

Leveraging prognostic baseline variables to gain precision in randomized trials

PubMed Central

Colantuoni, Elizabeth; Rosenblum, Michael

2015-01-01

We focus on estimating the average treatment effect in a randomized trial. If baseline variables are correlated with the outcome, then appropriately adjusting for these variables can improve precision. An example is the analysis of covariance (ANCOVA) estimator, which applies when the outcome is continuous, the quantity of interest is the difference in mean outcomes comparing treatment versus control, and a linear model with only main effects is used. ANCOVA is guaranteed to be at least as precise as the standard unadjusted estimator, asymptotically, under no parametric model assumptions and also is locally semiparametric efficient. Recently, several estimators have been developed that extend these desirable properties to more general settings that allow any real-valued outcome (e.g., binary or count), contrasts other than the difference in mean outcomes (such as the relative risk), and estimators based on a large class of generalized linear models (including logistic regression). To the best of our knowledge, we give the first simulation study in the context of randomized trials that compares these estimators. Furthermore, our simulations are not based on parametric models; instead, our simulations are based on resampling data from completed randomized trials in stroke and HIV in order to assess estimator performance in realistic scenarios. We provide practical guidance on when these estimators are likely to provide substantial precision gains and describe a quick assessment method that allows clinical investigators to determine whether these estimators could be useful in their specific trial contexts. PMID:25872751

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women’s Health Initiative Randomized Trial

PubMed Central

Anderson, G. L.; Sarto, G. E.; Haque, R.; Runowicz, C. D.; Aragaki, A. K.; Thomson, C. A.; Howard, B. V.; Wactawski-Wende, J.; Chen, C.; Rohan, T. E.; Simon, M. S.; Reed, S. D.; Manson, J. E.

2016-01-01

Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women’s Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results: After 5.6 years’ median intervention and 13 years’ median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. PMID:26668177

The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions

PubMed Central

Esserman, Denise; Allore, Heather G.; Travison, Thomas G.

2016-01-01

Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters. PMID:27478520

Study Design and Rationale of "A Multicenter, Open-Labeled, Randomized Controlled Trial Comparing MIdazolam Versus MOrphine in Acute Pulmonary Edema": MIMO Trial.

PubMed

Dominguez-Rodriguez, Alberto; Burillo-Putze, Guillermo; Garcia-Saiz, Maria Del Mar; Aldea-Perona, Ana; Harmand, Magali González-Colaço; Mirò, Oscar; Abreu-Gonzalez, Pedro

2017-04-01

Morphine has been used for several decades in cases of acute pulmonary edema (APE) due to the anxiolytic and vasodilatory properties of the drug. The non-specific depression of the central nervous system is probably the most significant factor for the changes in hemodynamics in APE. Retrospective studies have shown both negative and neutral effects in patients with APE and therefore some authors have suggested benzodiazepines as an alternative treatment. The use of intravenous morphine in the treatment of APE remains controversial. The MIdazolan versus MOrphine in APE trial (MIMO) is a multicenter, prospective, open-label, randomized study designed to evaluate the efficacy and safety of morphine in patients with APE. The MIMO trial will evaluate as a primary endpoint whether intravenous morphine administration improves clinical outcomes defined as in-hospital mortality. Secondary endpoint evaluation will be mechanical ventilation, cardiopulmonary resuscitation, intensive care unit admission rate, intensive care unit length of stay, and hospitalization length. In the emergency department, morphine is still used for APE in spite of poor scientific background data. The data from the MIMO trial will establish the effect-and especially the risk-when using morphine for APE.

Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial.

PubMed

Maruani, Annabel; Boutron, Isabelle; Baron, Gabriel; Ravaud, Philippe

2014-09-19

To evaluate the impact of sending an email to responsible parties of completed trials that do not comply with the Food and Drug Administration Amendments Act 801 legislation, to remind them of the legal requirement to post results. Cohort embedded pragmatic randomized controlled trial. Trials registered on ClinicalTrials.gov. 190 out of 379 trials randomly selected by computer generated randomization list to receive the intervention (personalized emails structured as a survey and sent by one of us to responsible parties of the trials, indirectly reminding them of the legal requirement and potential penalties for non-compliance). The primary outcome was the proportion of results posted on ClinicalTrials.gov at three months. The secondary outcome was the proportion posted at six months. In a second step, two assessors blinded to the intervention group collected the date of the first results being received on ClinicalTrials.gov. A post hoc sensitivity analysis excluding trials wrongly included was performed. Among 379 trials included, 190 were randomized to receive the email intervention. The rate of posting of results did not differ at three months between trials with or without the intervention: 36/190 (19%) v 24/189 (13%), respectively (relative risk 1.5, 95% confidence interval 0.9 to 2.4, P=0.096) but did at six months: 46/190 (24%) v 27/189 (14%), 1.7, 1.1 to 2.6, P=0.014. In the sensitivity analysis, which excluded 48/379 trials (13%), 26/190 (14%) and 22/189 (12%), respectively, results were significant at three months (relative risk 5.1, 1.1 to 22.9, P=0.02) and at six months (4.1, 1.3 to 10.6, P=0.001). Sending email reminders about the FDA's legal requirement to post results at ClinicalTrials.gov improved significantly the posting rate at six months but not at three months.Trial registration ClinicalTrials.gov NCT01658254. © Maruani et al 2014.

Widespread sucralose exposure in a randomized clinical trial in healthy young adults.

PubMed

Sylvetsky, Allison C; Walter, Peter J; Garraffo, H Martin; Robien, Kim; Rother, Kristina I

2017-04-01

Background : Low-calorie sweeteners (LCSs) are found in many foods and beverages, but consumers may not realize their presence, and their role in appetite, weight, and health is controversial. Although consumption limits based on toxicologic safety are well established, the threshold required to exert clinically relevant metabolic effects is unknown. Objectives: This study aimed to determine whether individuals who do not report consumption of LCSs can be correctly characterized as "unexposed" and to investigate whether instructions to avoid LCSs are effective in minimizing exposure. Design: Eighteen healthy 18- to 35-y-old "nonconsumers" (<1 food or beverage with LCSs/mo) enrolled in a 2-wk trial designed to evaluate the effects of LCSs on the gut microbiota. The trial consisted of 3 visits. At baseline, participants were counseled extensively about avoiding LCSs. After the run-in, participants were randomly assigned to consume diet soda containing sucralose or carbonated water (control) 3 times/d for 1 wk. Food diaries were maintained throughout the study, and a spot urine sample was collected at each visit. Results: At baseline, 8 participants had sucralose in their urine (29.9-239.0 ng/mL; mean ± SD: 111.4 ± 91.5 ng/mL). After the run-in, sucralose was found in 8 individuals (2 of whom did not have detectable sucralose at baseline) and ranged from 25.0 to 1062.0 ng/mL (mean ± SD: 191.7 ± 354.2 ng/mL). Only 1 participant reported consumption of an LCS-containing food before her visit. After the intervention, sucralose was detected in 3 individuals randomly assigned to receive carbonated water (26-121 ng/mL; mean ± SD: 60.7 ± 52.4 ng/mL). Conclusions: Despite the selection of healthy volunteers with minimal reported LCS consumption, more than one-third were exposed to sucralose at baseline and/or before randomization, and nearly half were exposed after assignment to the control. This shows that instructions to avoid LCSs are not effective and that

A randomized physiotherapy trial in patients with fecal incontinence: design of the PhysioFIT-study

PubMed Central

Bols, Esther MJ; Berghmans, Bary CM; Hendriks, Erik JM; de Bie, Rob A; Melenhorst, Jarno; van Gemert, Wim G; Baeten, Cor GMI

2007-01-01

Background Fecal incontinence (FI) is defined as the recurrent involuntary excretion of feces in inappropriate places or at inappropriate times. It is a major and highly embarrassing health care problem which affects about 2 to 24% of the adult population. The prevalence increases with age in both men and women. Physiotherapy interventions are often considered a first-line approach due to its safe and non-invasive nature when dietary and pharmaceutical treatment fails or in addition to this treatment regime. Two physiotherapy interventions, rectal balloon training (RBT) and pelvic floor muscle training (PFMT) are widely used in the management of FI. However, their effectiveness remains uncertain since well-designed trials on the effectiveness of RBT and PFMT versus PFMT alone in FI have never been published. Methods/Design A two-armed randomized controlled clinical trial will be conducted. One hundred and six patients are randomized to receive either PFMT combined with RBT or PFMT alone. Physicians in the University Hospital Maastricht include eligible participants. Inclusion criteria are (1) adults (aged ≥ 18 years), (2) with fecal incontinence complaints due to different etiologies persisting for at least six months, (3) having a Vaizey incontinence score of at least 12, (4) and failure of conservative treatment (including dietary adaptations and pharmacological agents). Baseline measurements consist of the Vaizey incontinence score, medical history, physical examination, medication use, anorectal manometry, rectal capacity measurement, anorectal sensation, anal endosonography, defecography, symptom diary, Fecal Incontinence Quality of Life scale (FIQL) and the PREFAB-score. Follow-up measurements are scheduled at three, six and 12 months after inclusion. Skilled and registered physiotherapists experienced in women's health perform physiotherapy treatment. Twelve sessions are administered during three months according to a standardized protocol. Discussion This

A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

PubMed Central

Lapidus, Kyle A.B.; Levitch, Cara F.; Perez, Andrew M.; Brallier, Jess W.; Parides, Michael K.; Soleimani, Laili; Feder, Adriana; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.

2014-01-01

Background The N-methyl-d-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods Twenty patients with major depression were randomized and 18 completed two treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized, double-blind, crossover study. The primary efficacy outcome measure was change in depression severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results Patients showed significant improvement in depressive symptoms at 24 hours following ketamine compared to placebo [t=4.39, p<0.001; estimated mean MADRS score difference of 7.6 ± 3.7 (95% CI: 3.9 – 11.3)]. Eight of 18 patients (44%) met response criteria 24 hours following ketamine administration, compared to 1 of 18 (6%) following placebo (p=0.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. Trial Registration clinicaltrials.gov identifier NCT01304147 PMID:24821196

A cluster-randomized, placebo-controlled, maternal vitamin a or beta-carotene supplementation trial in bangladesh: design and methods

PubMed Central

2011-01-01

Background We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field. Methods This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies. Results The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant

Immigrant family skills-building to prevent tobacco use in Latino youth: study protocol for a community-based participatory randomized controlled trial

PubMed Central

2012-01-01

Background Despite declines over recent years, youth tobacco and other substance use rates remain high. Latino youth are at equal or increased risk for lifetime tobacco, alcohol, marijuana, and other illicit drug use compared with their white peers. Family plays an important and influential role in the lives of youth, and longitudinal research suggests that improving parenting skills may reduce youth substance use. However, few interventions are oriented towards immigrant Latino families, and none have been developed and evaluated using a community-based participatory research (CBPR) process that may increase the effectiveness and sustainability of such projects. Therefore, using CBPR principles, we developed a randomized clinical trial to assess the efficacy of a family-skills training intervention to prevent tobacco and other substance use intentions in Latino youth. Methods/Design In collaboration with seven Latino community-serving agencies, we will recruit and randomize 336 immigrant families, into intervention or delayed treatment conditions. The primary outcome is youth intention to smoke 6 months post intervention. The intervention consists of eight parent and four youth sessions targeting parenting skills and parent–youth relational factors associated with lower smoking and other substance use in youth. Discussion We present the study protocol for a family intervention using a CBPR randomized clinical trial to prevent smoking among Latino youth. The results of this trial will contribute to the limited information on effective and sustainable primary prevention programs for tobacco and other substance use directed at the growing US Latino communities. Trial registration ClinicalTrials.gov: NCT01442753 PMID:23253201

Randomized Control Trials on the Dynamic Geometry Approach

ERIC Educational Resources Information Center

Jiang, Zhonghong; White, Alexander; Rosenwasser, Alana

2011-01-01

The project reported here is conducting repeated randomized control trials of an approach to high school geometry that utilizes Dynamic Geometry (DG) software to supplement ordinary instructional practices. It compares effects of that intervention with standard instruction that does not make use of computer drawing/exploration tools. The basic…

A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization.

PubMed

Brown, Alexandra R; Gajewski, Byron J; Aaronson, Lauren S; Mudaranthakam, Dinesh Pal; Hunt, Suzanne L; Berry, Scott M; Quintana, Melanie; Pasnoor, Mamatha; Dimachkie, Mazen M; Jawdat, Omar; Herbelin, Laura; Barohn, Richard J

2016-08-31

In the last few decades, the number of trials using Bayesian methods has grown rapidly. Publications prior to 1990 included only three clinical trials that used Bayesian methods, but that number quickly jumped to 19 in the 1990s and to 99 from 2000 to 2012. While this literature provides many examples of Bayesian Adaptive Designs (BAD), none of the papers that are available walks the reader through the detailed process of conducting a BAD. This paper fills that gap by describing the BAD process used for one comparative effectiveness trial (Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations) that can be generalized for use by others. A BAD was chosen with efficiency in mind. Response-adaptive randomization allows the potential for substantially smaller sample sizes, and can provide faster conclusions about which treatment or treatments are most effective. An Internet-based electronic data capture tool, which features a randomization module, facilitated data capture across study sites and an in-house computation software program was developed to implement the response-adaptive randomization. A process for adapting randomization with minimal interruption to study sites was developed. A new randomization table can be generated quickly and can be seamlessly integrated in the data capture tool with minimal interruption to study sites. This manuscript is the first to detail the technical process used to evaluate a multisite comparative effectiveness trial using adaptive randomization. An important opportunity for the application of Bayesian trials is in comparative effectiveness trials. The specific case study presented in this paper can be used as a model for conducting future clinical trials using a combination of statistical software and a web-based application. ClinicalTrials.gov Identifier: NCT02260388 , registered on 6 October 2014.

Health education for microcredit clients in Peru: a randomized controlled trial

PubMed Central

2011-01-01

Background Poverty, lack of female empowerment, and lack of education are major risk factors for childhood illness worldwide. Microcredit programs, by offering small loans to poor individuals, attempt to address the first two of these risk factors, poverty and gender disparity. They provide clients, usually women, with a means to invest in their businesses and support their families. This study investigates the health effects of also addressing the remaining risk factor, lack of knowledge about important health issues, through randomization of members of a microcredit organization to receive a health education module based on the World Health Organization's Integrated Management of Childhood Illness (IMCI) community intervention. Methods Baseline data were collected in February 2007 from clients of a microcredit organization in Pucallpa, Peru (n = 1,855) and their children (n = 598). Loan groups, consisting of 15 to 20 clients, were then randomly assigned to receive a health education intervention involving eight monthly 30-minute sessions given by the organization's loan officers at monthly loan group meetings. In February 2008, follow-up data were collected, and included assessments of sociodemographic information, knowledge of child health issues, and child health status (including child height, weight, and blood hemoglobin levels). To explore the effects of treatment (i.e., participation in the health education sessions) on the key outcome variables, multivariate regressions were implemented using ordinary least squares. Results Individuals in the IMCI treatment arm demonstrated more knowledge about a variety of issues related to child health, but there were no changes in anthropometric measures or reported child health status. Conclusions Microcredit clients randomized to an IMCI educational intervention showed greater knowledge about child health, but no differences in child health outcomes compared to controls. These results imply that the intervention did

Cluster randomized trials in comparative effectiveness research: randomizing hospitals to test methods for prevention of healthcare-associated infections.

PubMed

Platt, Richard; Takvorian, Samuel U; Septimus, Edward; Hickok, Jason; Moody, Julia; Perlin, Jonathan; Jernigan, John A; Kleinman, Ken; Huang, Susan S

2010-06-01

The need for evidence about the effectiveness of therapeutics and other medical practices has triggered new interest in methods for comparative effectiveness research. Describe an approach to comparative effectiveness research involving cluster randomized trials in networks of hospitals, health plans, or medical practices with centralized administrative and informatics capabilities. We discuss the example of an ongoing cluster randomized trial to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection in intensive care units (ICUs). The trial randomizes 45 hospitals to: (a) screening cultures of ICU admissions, followed by Contact Precautions if MRSA-positive, (b) screening cultures of ICU admissions followed by decolonization if MRSA-positive, or (c) universal decolonization of ICU admissions without screening. All admissions to adult ICUs. The primary outcome is MRSA-positive clinical cultures occurring >or=2 days following ICU admission. Secondary outcomes include blood and urine infection caused by MRSA (and, separately, all pathogens), as well as the development of resistance to decolonizing agents. Recruitment of hospitals is complete. Data collection will end in Summer 2011. This trial takes advantage of existing personnel, procedures, infrastructure, and information systems in a large integrated hospital network to conduct a low-cost evaluation of prevention strategies under usual practice conditions. This approach is applicable to many comparative effectiveness topics in both inpatient and ambulatory settings.

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

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

Yamoah, Kosj; Showalter, Timothy N.; Ohri, Nitin, E-mail: ohri.nitin@gmail.com

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: Inmore » primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.« less

Using Minitel Network and New Software Engineering Techniques for Randomized Clinical Trials Management

PubMed Central

Lepage, E.; Tavernier, H.; Bouhaddou, O.; Jais, JP.; Gisselbrecht, C.; Aurengo, A.; Boiron, M.

1989-01-01

The usual Randomized Clinical Trials (RCT) management using an anachronic procedure involving a flowsheet exchange between the remote centers and the coordinating center presents a number of inadequacies. Eligibility criteria are not always verified by the coordinating center before inclusion in the trial and randomization. Laboratory tests and therapeutic adjustments are frequently decided from memory by the clinician which often leads to data oversight and variability of therapeutic decisions. This results in protocol deviations and alteration of the efficiency of the RCT. HICREN is a medical consultation system designed to take into account the different difficulties encountered during RCT driving. The system integrates a clinical database with artificial intelligence technics to manage clinical trial data on non-expensive and widely available Minitel® terminals. Randomization is then possible, after eligibility criteria are satisfied, anytime and anywhere in France through the national telematic network. HICREN also includes an intuitive graphic interface to increase physician's compliance: a user friendly dialogue manager supports on line data entry with multi-windowing facilities and pull down menus. Interactive data validation is achieved through an interface to dedicated C programs. Patient follow up is achieved by an expert system that proposes appropriate dose of treatment according to the rules defined in the trial. At present, HICREN is implemented on the CISARC system for conducting three randomized clinical trials and one epidemiologic study.

Review of Randomized Controlled Trials of Massage in Preterm Infants

PubMed Central

Niemi, Anna-Kaisa

2017-01-01

Preterm birth affects about 10% of infants born in the United States. Massage therapy is being used in some neonatal intensive care units for its potential beneficial effects on preterm infants. This article reviews published randomized controlled trials on the effects of massage in preterm infants. Most studies evaluating the effect of massage in weight gain in premature infants suggest a positive effect on weight gain. Increase in vagal tone has been reported in infants who receive massage and has been suggested as a possible mechanism for improved weight gain. More studies are needed on the underlying mechanisms of the effects of massage therapy on weight gain in preterm infants. While some trials suggest improvements in developmental scores, decreased stress behavior, positive effects on immune system, improved pain tolerance and earlier discharge from the hospital, the number of such studies is small and further evidence is needed. Further studies, including randomized controlled trials, are needed on the effects of massage in preterm infants. PMID:28368368

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

PubMed Central

Viguiliouk, Effie; Kendall, Cyril W. C.; Blanco Mejia, Sonia; Cozma, Adrian I.; Ha, Vanessa; Mirrahimi, Arash; Jayalath, Viranda H.; Augustin, Livia S. A.; Chiavaroli, Laura; Leiter, Lawrence A.; de Souza, Russell J.; Jenkins, David J. A.; Sievenpiper, John L.

2014-01-01

Background Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent. Objective To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes. Data Sources MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014. Study Selection Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR. Data Extraction and Synthesis Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2). Results Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts. Limitations Majority of trials were of short duration and poor quality. Conclusions Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates. Trial Registration ClinicalTrials.gov NCT01630980 PMID:25076495

Automatic generation of randomized trial sequences for priming experiments.

PubMed

Ihrke, Matthias; Behrendt, Jörg

2011-01-01

In most psychological experiments, a randomized presentation of successive displays is crucial for the validity of the results. For some paradigms, this is not a trivial issue because trials are interdependent, e.g., priming paradigms. We present a software that automatically generates optimized trial sequences for (negative-) priming experiments. Our implementation is based on an optimization heuristic known as genetic algorithms that allows for an intuitive interpretation due to its similarity to natural evolution. The program features a graphical user interface that allows the user to generate trial sequences and to interactively improve them. The software is based on freely available software and is released under the GNU General Public License.

Sexual assault resistance education for university women: study protocol for a randomized controlled trial (SARE trial)

PubMed Central

2013-01-01

Background More than one in six women will be sexually assaulted in their lifetimes, most by men they know. The situation on university campuses is even more startling, with as many as 1 in 4 female students being victims of rape or attempted rape. The associated physical and mental health effects are extensive and the social and economic costs are staggering. The aim of this randomized controlled trial is to determine whether a novel, small-group sexual assault resistance education program can reduce the incidence of sexual assault among university-attending women, when compared to current university practice of providing informational brochures. Methods/Design The trial will evaluate a theoretically and empirically sound four-unit, 12-hour education program that has been demonstrated in pilot studies to have short-term efficacy. Three of the four units provide information, skills, and practice aimed at decreasing the time needed for women to assess situations with elevated risk of acquaintance sexual assault as dangerous and to take action, reducing emotional obstacles to taking action, and increasing the use of the most effective methods of verbal and physical self-defense. The fourth unit focuses on facilitating a stronger positive sexuality from which women may resist sexual coercion by male intimates more successfully. The trial will extend the pilot evaluations by expanding the participant pool and examining the long term efficacy of the program. A total of 1716 first-year female students (age 17 to 24 years) from three Canadian universities will be enrolled. The primary outcome is completed sexual assault, measured by The Sexual Experiences Survey - Short Form Victimization instrument. Secondary outcomes include changes in knowledge, attitudes, and skills related to the process of sexual assault resistance. Outcomes will be measured at baseline, 1 week, 6, 12, 18, and 24 months. Discussion The results of the trial will be used to produce a maximally

Comparing Two Web-Based Smoking Cessation Programs: Randomized Controlled Trial

PubMed Central

McKay, H Garth; Seeley, John R; Lichtenstein, Edward; Gau, Jeff M

2008-01-01

Background Smoking cessation remains a significant public health problem. Innovative interventions that use the Internet have begun to emerge that offer great promise in reaching large numbers of participants and encouraging widespread behavior change. To date, the relatively few controlled trials of Web-based smoking cessation programs have been limited by short follow-up intervals. Objective We describe the 6-month follow-up results of a randomized controlled trial in which participants recruited online were randomly assigned to either a Web-based smoking cessation program (Quit Smoking Network; QSN) or a Web-based exercise enhancement program (Active Lives) adapted somewhat to encourage smoking cessation. Methods The study was a two-arm randomized controlled trial that compared two Web-based smoking cessation programs: (1) the QSN intervention condition presented cognitive-behavioral strategies, and (2) the Active Lives control condition provided participants with guidance in developing a physical activity program to assist them with quitting. The QSN condition provided smoking cessation information and behavior change strategies while the Active Lives condition provided participants with physical activity recommendations and goal setting. The QSN condition was designed to be more engaging (eg, it included multimedia components) and to present much greater content than is typically found in smoking cessation programs. Results Contrary to our hypotheses, no between-condition differences in smoking abstinence were found at 3- and 6-month follow-up assessments. While participants in the QSN intervention condition spent more time than controls visiting the online program, the median number of 1.0 visit in each condition and the substantial attrition (60.8% at the 6-month follow-up) indicate that participants were not as engaged as we had expected. Conclusions Contrary to our hypothesis, our test of two Web-based smoking cessation conditions, an intervention and an

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

PubMed Central

2013-01-01

Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed

Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH): A randomized controlled trial study protocol

PubMed Central

2011-01-01

Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33%) do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention) or control (no change). At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI) and standardized body mass index (zBMI). Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous), Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight management programs. Trial

Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial

PubMed Central

2013-01-01

Background Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship. Methods In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance. Results Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA. Conclusions In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD. Trial registration ClinicalTrials.gov identifier: NCT01136564 PMID:23889806

Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction.

PubMed

Penny, William F; Hammond, H Kirk

2017-05-01

Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart failure with reduced ejection fraction (HFrEF) have been published. Each enrolled patients with stable symptomatic HFrEF and used either intracoronary delivery of a virus vector or endocardial injection of a plasmid. The initial CUPID trial randomized 14 subjects to placebo and 25 subjects to escalating doses of adeno-associated virus type 1 encoding sarcoplasmic reticulum calcium ATPase (AAV1.SERCA2a). AAV1.SERCA2a was well tolerated, and the high-dose group met a 6 month composite endpoint. In the subsequent CUPID-2 study, 243 subjects received either placebo or the high dose of AAV1.SERCA2a. AAV1.SERCA2a administration, while safe, failed to meet the primary or any secondary endpoints. STOP-HF used plasmid endocardial injection of stromal cell-derived factor-1 to promote stem-cell recruitment. In a 93-subject trial of patients with ischemic etiology heart failure, the primary endpoint (symptoms and 6 min walk distance) failed, but subgroup analyses showed improvements in subjects with the lowest ejection fractions. A fourth trial randomized 14 subjects to placebo and 42 subjects to escalating doses of adenovirus-5 encoding adenylyl cyclase 6 (Ad5.hAC6). There were no safety concerns, and patients in the two highest dose groups (combined) showed improvements in left ventricular function (left ventricular ejection fraction and -dP/dt). The safety data from four randomized clinical trials of gene transfer in patients with symptomatic HFrEF suggest that this approach can be conducted with acceptable risk, despite invasive delivery techniques in a high-risk population. Additional trials are necessary before the approach can be endorsed for clinical

Financial management of a large multisite randomized clinical trial.

PubMed

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial

PubMed Central

Cheung, Angela M; Tile, Lianne; Lee, Yuna; Tomlinson, George; Hawker, Gillian; Scher, Judy; Hu, Hanxian; Vieth, Reinhold; Thompson, Lilian; Jamal, Sophie; Josse, Robert

2008-01-01

Background Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures. Methods and Findings This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0

A Multicenter, Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

PubMed Central

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D’Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D’Incecco, Carmine; Barlafante, Gina

2015-01-01

Background Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. Materials and Methods The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. Results A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Conclusions Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. PMID:25974071

Moxibustion for pain relief in patients with primary dysmenorrhea: A randomized controlled trial

PubMed Central

Bo, Linna; Lao, Lixing; Chen, Jiao; Yu, Siyi; Yu, Zheng; Tang, Hongzhi; Yi, Ling; Wu, Xi; Yang, Jie; Liang, Fanrong

2017-01-01

Background Though moxibustion is frequently used to treat primary dysmenorrhea in China, relevant evidence supporting its effectiveness is still scanty. Methods This study was a pragmatic randomized, conventional drug controlled, open-labeled clinical trial. After initial screen, 152 eligible participants were averagely randomized to receive two different treatment strategies: Moxibustion and conventional drugs. Participants and practitioners were not blinded in this study. The duration of each treatment was 3 months. The primary outcome was pain relief measured by the Visual Analogue Scale. The menstrual pain severity was recorded in a menstrual pain diary. Results 152 eligible patients were included but only 133 of them eventually completed the whole treatment course. The results showed that the menstrual pain intensity in experimental group and control group was reduced from 6.38±1.28 and 6.41±1.29, respectively, at baseline, to 2.54±1.41 and 2.47±1.29 after treatment. The pain reduction was not significantly different between these two groups (P = 0.76), however; the pain intensity was significantly reduced relative to baseline for each group (P<0.01). Three months after treatment, the effectiveness of moxibustion sustained and started to be superior to the drug’s effect (-0.87, 95%CI -1.32 to -0.42, P<0.01). Secondary outcome analyses showed that moxibustion was as effective as drugs in alleviating menstrual pain-related symptoms. The serum levels of pain mediators, such as PGF2α, OT, vWF, β-EP, PGE2, were significantly improved after treatment in both groups (P<0.05). No adverse events were reported in this trial. Conclusions Both moxibustion and conventional drug showed desirable merits in managing menstrual pain, given their treatment effects and economic costs. This study as a pragmatic trial only demonstrates the effectiveness, not the efficacy, of moxibustion for menstrual pain. It can’t rule out the effect of psychological factors during

Social networking technologies as emerging tools for HIV prevention: A Cluster Randomized Trial

PubMed Central

Young, Sean D.; Cumberland, William G.; Lee, Sung-Jae; Jaganath, Devan; Szekeres, Greg; Coates, Thomas

2013-01-01

Background Social networking technologies are an emerging tool for HIV prevention. Objective To determine whether social networking communities can increase HIV testing among African American and Latino men who have sex with men (MSM). Design Randomized; controlled trial with concealed allocation (ClinicalTrials.gov: NCT01701206). Setting Online. Patients 112 MSM based in Los Angeles, more than 85% of whom were African American or Latino. Intervention Sixteen peer leaders were randomly assigned to deliver information about HIV or general health to participants via Facebook groups over 12 weeks. After participants accepted a request to join the group, participation was voluntary. Group participation and engagement was monitored. Participants could request a free home-based HIV testing kit and completed questionnaires at baseline and 12-week follow-up. Measurements Participant acceptance of and engagement in the intervention and social network participation, rates of home-based HIV testing, and sexual risk behaviors. Results Almost 95% of intervention participants and 73% of control participants voluntarily communicated using the social platform. Twenty-five of the 57 intervention participants (44%) requested home-based HIV testing kits compared with 11 of 55 control participants (20%) (difference, 24 percentage points [95% CI, 8 to 41 percentage points]). Nine of the 25 intervention participants (36%) who requested the test took it and mailed it back compared with 2 of the 11 control participants (18%) who requested the test. Retention at study follow-up was more 93%. Limitations Only 2 Facebook communities were included for each group. Conclusions Social networking communities are acceptable and effective tools to increase home-based HIV testing among at-risk populations. Primary funding source National Institute of Mental Health ClinicalTrials.gov Identifier (NCT01701206) PMID:24026317

Exercise Improves Cognition in Parkinson’s Disease: the PRET-PD Randomized Clinical Trial

PubMed Central

David, Fabian J.; Robichaud, Julie A.; Leurgans, Sue E.; Poon, Cynthia; Kohrt, Wendy M.; Goldman, Jennifer G.; Comella, Cynthia L.; Vaillancourt, David E.; Corcos, Daniel M.

2015-01-01

Background This paper reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes which were gathered as part of the Progressive Resistance Exercise Training in Parkinson’s disease randomized controlled trial. Methods This study was a prospective, parallel-group, single-center trial. Fifty-one non-demented patients with mild-to-moderate Parkinson’s disease were randomly assigned either to modified Fitness Counts or to Progressive Resistance Exercise, and were followed for 24 months. Cognitive outcomes were the Digit Span, Stroop, and Brief Test of Attention. Results Eighteen patients in modified Fitness Counts and 20 patients in Progressive Resistance Exercise completed the trial. At 12 and at 24 months no differences between groups were observed. At 12 months, relative to baseline, modified Fitness Counts improved on the Digit Span (estimated change, 0.3; Inter-Quartile Range, 0, 0.7; p=0.04) and Stroop (0.3; 0, 0.6; p=0.04), and Progressive Resistance Exercise improved only on the Digit Span (0.7; 0.3, 1; p<0.01). At 24 months, relative to baseline, modified Fitness Counts improved on the Digit Span (0.7; 0.3, 1.7; p<0.01) and Stroop (0.3; 0.1, 0.5; p=0.03), while Progressive Resistance Exercise improved on the Digit Span (0.5; 0.2, 0.8; p<0.01), Stroop (0.2; −0.1, 0.6; p=0.048), and Brief Test of Attention (0.3; 0, 0.8; p=0.048). No neurologic or cognitive adverse events were seen. Conclusions This study provides Class IV level of evidence that 24 months of Progressive Resistance Exercise or modified Fitness Counts may improve attention and working memory in non-demented patients with mild-to-moderate Parkinson’s disease. PMID:26148003

A worksite prevention program for construction workers: design of a randomized controlled trial

PubMed Central

2010-01-01

Background A worksite prevention program was developed to promote the work ability of construction workers and thereby prolong a healthy working life. The objective of this paper is to present the design of a randomized controlled trial evaluating the effectiveness of that intervention program compared with usual care for construction workers. Methods The study is designed as a randomized controlled trial with a follow-up of one year. Employees eligible for this study are construction workers performing actual construction work. The worksite intervention will be compared with usual care. This intervention was developed by using the Intervention Mapping approach and consists of the following components: (1) two individual training sessions of a physical therapist to lower the physical workload, (2) a Rest-Break tool to improve the balance between work and recovery, and (3) two empowerment training sessions to increase the influence of the construction workers at the worksite. Outcome measures are assessed at baseline, 3, 6, and 12 months. The primary outcome measures of this study are work ability and health-related quality of life. Secondary outcome measures include need for recovery, musculoskeletal complaints, work engagement and self efficacy. Cost-effectiveness will be evaluated from the company perspective. Moreover, a process evaluation will be conducted. Discussion The feasibility of the intervention and the study has been enhanced by creating an intervention program that explicitly appeals to construction workers and will not interfere too much with the ongoing construction. The feasibility and effectiveness of this worksite prevention program will be investigated by means of an effect- and a process evaluation. If proven effective, this worksite prevention program can be implemented on a larger scale within the construction industry. Trial Registration NTR1278 PMID:20546568

Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.

PubMed

Thompson, Patricia; Roe, Denise J; Fales, Liane; Buckmeier, Julie; Wang, Fang; Hamilton, Stanley R; Bhattacharyya, Achyut; Green, Sylvan; Hsu, Chiu-Hsieh; Chow, H-H Sherry; Ahnen, Dennis J; Boland, C Richard; Heigh, Russell I; Fay, David E; Martinez, Maria Elena; Jacobs, Elizabeth; Ashbeck, Erin L; Alberts, David S; Lance, Peter

2012-12-01

COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported. ©2012 AACR

The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants

PubMed Central

Zelkowitz, Phyllis; Feeley, Nancy; Shrier, Ian; Stremler, Robyn; Westreich, Ruta; Dunkley, David; Steele, Russell; Rosberger, Zeev; Lefebvre, Francine; Papageorgiou, Apostolos

2008-01-01

Background Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues) in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants. Methods and design Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals, and are randomly assigned to the experimental (Cues) intervention or to an attention control (Care) condition. The Cues intervention teaches mothers to attend to their own physiological, cognitive, and emotional cues that signal anxiety and worry, and to use cognitive-behavioural strategies to reduce distress. Mothers are also taught to understand infant cues and to respond sensitively to those cues. Mothers in the Care group receive general information about infant care. Both groups have 6 contacts with a trained intervener; 5 of the 6 sessions take place during the infant's hospitalization, and the sixth contact occurs after discharge, in the participant mother's home. The primary outcome is maternal symptoms of anxiety, assessed via self-report questionnaire immediately post-intervention. Secondary outcomes include maternal sensitive behaviour, maternal symptoms of posttraumatic stress, and infant development at 6 months corrected age. Discussion The Cues and Care trial will provide important information

The Effectiveness of Propolis on Gingivitis: A Randomized Controlled Trial

PubMed Central

Paulino, Niraldo; Nör, Jacques E.; Moreira, Alexandre

2014-01-01

Abstract Background: A randomized, double-blind, controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design. Methods: Twenty-one twin pairs (n=42) were enrolled in a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction (21 days). During the gingivitis induction phase, one member of the twin pair was randomly assigned to a 2% typified propolis rinse, and the other was assigned a color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21 days. Gingivitis was measured on days −14 (baseline), 0 (after hygiene phase), and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and by standard digital imaging of the gum tissues (G-parameter). Results: The 38 persons who completed the study (age 13–22 years) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase. After 21 days without oral hygiene, the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter. Conclusions: Use of a 2% typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period. PMID:25380344

Randomized Trial of Drug Abuse Treatment-Linkage Strategies

ERIC Educational Resources Information Center

Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

2005-01-01

A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial

PubMed Central

2012-01-01

Background Small incision lenticule extraction or SMILE is a novel form of ‘flapless’ corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively. Methods/Design Single tertiary center, parallel group, single-masked, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 diopter (D)) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 D of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-masked trial, subjects and their caregivers will be masked to the assigned

Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Subarachnoid hemorrhage is a common and dangerous disease with an unfavorable prognosis. Patients with poor-grade subarachnoid hemorrhage (Hunt & Hess Grades 4–5) are unconscious on admission. Because of the high mortality and disability rate associated with poor-grade subarachnoid hemorrhage, it is often treated conservatively. Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aims to identify the optimal time to operate on patients admitted in poor clinical condition. Methods/design Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality. Discussion This is the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients. Trial registration Chinese Clinical Trial Registry: ChiCTR-TRC-12002917 PMID:23957458

Treatment of Anxiety in Patients with Coronary Heart Disease: Rationale and Design of the UNWIND Randomized Clinical Trial

PubMed Central

Blumenthal, James A.; Feger, Bryan J.; Smith, Patrick J.; Watkins, Lana L.; Jiang, Wei; Davidson, Jonathan; Hoffman, Benson M.; Ashworth, Megan; Mabe, Stephanie K.; Babyak, Michael A.; Kraus, William E.; Hinderliter, Alan; Sherwood, Andrew

2016-01-01

Background Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. Methods The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70–85% VO2peak), escitalopram (5–20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. Conclusions The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients. PMID:27264220

Randomized controlled trials in dentistry: common pitfalls and how to avoid them.

PubMed

Fleming, Padhraig S; Lynch, Christopher D; Pandis, Nikolaos

2014-08-01

Clinical trials are used to appraise the effectiveness of clinical interventions throughout medicine and dentistry. Randomized controlled trials (RCTs) are established as the optimal primary design and are published with increasing frequency within the biomedical sciences, including dentistry. This review outlines common pitfalls associated with the conduct of randomized controlled trials in dentistry. Common failings in RCT design leading to various types of bias including selection, performance, detection and attrition bias are discussed in this review. Moreover, methods of minimizing and eliminating bias are presented to ensure that maximal benefit is derived from RCTs within dentistry. Well-designed RCTs have both upstream and downstream uses acting as a template for development and populating systematic reviews to permit more precise estimates of treatment efficacy and effectiveness. However, there is increasing awareness of waste in clinical research, whereby resource-intensive studies fail to provide a commensurate level of scientific evidence. Waste may stem either from inappropriate design or from inadequate reporting of RCTs; the importance of robust conduct of RCTs within dentistry is clear. Optimal reporting of randomized controlled trials within dentistry is necessary to ensure that trials are reliable and valid. Common shortcomings leading to important forms or bias are discussed and approaches to minimizing these issues are outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epilepsy and Neuromodulation—Randomized Controlled Trials

PubMed Central

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

2018-01-01

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

A Two Year Randomized Controlled Trial of Progressive Resistance Exercise for Parkinson’s Disease

PubMed Central

Corcos, Daniel M.; Robichaud, Julie A.; David, Fabian J.; Leurgans, Sue E.; Vaillancourt, David E.; Poon, Cynthia; Rafferty, Miriam R.; Kohrt, Wendy M.; Comella, Cynthia L.

2013-01-01

Background The effects of progressive resistance exercise (PRE) on the motor signs of Parkinson’s disease have not been studied in controlled trials. Our aim was to compare 6, 12, 18, and 24 month outcomes of patients with Parkinson’s disease who received PRE to a stretching, balance, and strengthening exercise program. Methods We conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients, matched by sex and off-medication Unified Parkinson’s Disease Rating Scale, motor subscale (UPDRS-III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight lifting program. The Modified Fitness Counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised two days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first six months and one weekly session after six months. The primary outcome was the off-medication UPDRS-III score. Patients were followed for 24 months at six-month intervals. Results Of 51 patients, 20 in PRE and 18 in mFC completed the trial. At 24 months, the mean off-medication UPDRS-III score decreased more with PRE than with mFC (mean difference: - 7·3 points; 95% CI: -11·3 to -3·6; P < 0·001). The PRE group had ten adverse events. The mFC group had seven adverse events. Conclusions PRE demonstrated a statistically and clinically significant reduction in UPDRS-III scores compared to mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs. PMID:23536417

Mobile Phone-Delivered Cognitive Behavioral Therapy for Insomnia: A Randomized Waitlist Controlled Trial

PubMed Central

Lancee, Jaap; Griffioen-Both, Fiemke; Spruit, Sandor; Fitrianie, Siska; Neerincx, Mark A; Beun, Robbert Jan; Brinkman, Willem-Paul

2017-01-01

Background This study is one of the first randomized controlled trials investigating cognitive behavioral therapy for insomnia (CBT-I) delivered by a fully automated mobile phone app. Such an app can potentially increase the accessibility of insomnia treatment for the 10% of people who have insomnia. Objective The objective of our study was to investigate the efficacy of CBT-I delivered via the Sleepcare mobile phone app, compared with a waitlist control group, in a randomized controlled trial. Methods We recruited participants in the Netherlands with relatively mild insomnia disorder. After answering an online pretest questionnaire, they were randomly assigned to the app (n=74) or the waitlist condition (n=77). The app packaged a sleep diary, a relaxation exercise, sleep restriction exercise, and sleep hygiene and education. The app was fully automated and adjusted itself to a participant’s progress. Program duration was 6 to 7 weeks, after which participants received posttest measurements and a 3-month follow-up. The participants in the waitlist condition received the app after they completed the posttest questionnaire. The measurements consisted of questionnaires and 7-day online diaries. The questionnaires measured insomnia severity, dysfunctional beliefs about sleep, and anxiety and depression symptoms. The diary measured sleep variables such as sleep efficiency. We performed multilevel analyses to study the interaction effects between time and condition. Results The results showed significant interaction effects (P<.01) favoring the app condition on the primary outcome measures of insomnia severity (d=–0.66) and sleep efficiency (d=0.71). Overall, these improvements were also retained in a 3-month follow-up. Conclusions This study demonstrated the efficacy of a fully automated mobile phone app in the treatment of relatively mild insomnia. The effects were in the range of what is found for Web-based treatment in general. This supports the applicability of

Randomized Clinical Trial of Interceptive and Comprehensive Orthodontics

PubMed Central

King, G.J.; Spiekerman, C.F.; Greenlee, G.M.; Huang, G.J.

2012-01-01

Focusing public insurance programs on interceptive orthodontics (IO) may increase access for low-income children. This report presents outcomes from a randomized clinical trial (RCT) comparing IO with comprehensive orthodontics (CO) in Medicaid patients. One hundred seventy pre-adolescents with Medicaid-eligible malocclusions were randomized to IO (n = 86) followed by observation (OBS) or OBS followed by CO (n = 84). One hundred thirty-four completed the trial. Models at pre-treatment (baseline) and following ≤ 2 years of intervention and 2 years of OBS (48 mos) were scored by calibrated examiners using the Peer Assessment Rating (PAR) and Index of Complexity, Outcome and Need (ICON). Overall outcomes and clinically meaningful categorical ICON data on need/acceptability, complexity, and improvement were compared. At baseline, groups were balanced by age, gender, ethnicity, and PAR/ICON scores. Most were minorities. Most (77%) were rated as difficult-to-very difficult. Scores improved significantly for both groups, but CO more than IO (PAR, 18.6 [95%CI 15.1, 22.1] vs.10.1 [95%CI 6.7, 13.4]; ICON, 44.8 [95% CI 39.7, 49.9] vs. 35.2 [95%CI 29.7, 40.6], respectively). On average, IO is effective at reducing malocclusions in Medicaid patients, but less than CO. (ClinicalTrials.gov number CT00067379) PMID:22699670

External validity of randomized controlled trials in older adults, a systematic review.

PubMed

van Deudekom, Floor J; Postmus, Iris; van der Ham, Danielle J; Pothof, Alexander B; Broekhuizen, Karen; Blauw, Gerard J; Mooijaart, Simon P

2017-01-01

To critically assess the external validity of randomized controlled trials (RCTs) it is important to know what older adults have been enrolled in the trials. The aim of this systematic review is to study what proportion of trials specifically designed for older patients report on somatic status, physical and mental functioning, social environment and frailty in the patient characteristics. PubMed was searched for articles published in 2012 and only RCTs were included. Articles were further excluded if not conducted with humans or only secondary analyses were reported. A random sample of 10% was drawn. The current review analyzed this random sample and further selected trials when the reported mean age was ≥ 60 years. We extracted geriatric assessments from the population descriptives or the in- and exclusion criteria. In total 1396 trials were analyzed and 300 trials included. The median of the reported mean age was 66 (IQR 63-70) and the median percentage of men in the trials was 60 (IQR 45-72). In 34% of the RCTs specifically designed for older patients somatic status, physical and mental functioning, social environment or frailty were reported in the population descriptives or the in- and exclusion criteria. Physical and mental functioning was reported most frequently (22% and 14%). When selecting RCTs on a mean age of 70 or 80 years the report of geriatric assessments in the patient characteristics was 46% and 85% respectively but represent only 5% and 1% of the trials. Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the results can be applied. We recommend systematic to transparently report these relevant characteristics of older participants included in RCTs.

Using re-randomization to increase the recruitment rate in clinical trials - an assessment of three clinical areas.

PubMed

Kahan, Brennan C

2016-12-13

Patient recruitment in clinical trials is often challenging, and as a result, many trials are stopped early due to insufficient recruitment. The re-randomization design allows patients to be re-enrolled and re-randomized for each new treatment episode that they experience. Because it allows multiple enrollments for each patient, this design has been proposed as a way to increase the recruitment rate in clinical trials. However, it is unknown to what extent recruitment could be increased in practice. We modelled the expected recruitment rate for parallel-group and re-randomization trials in different settings based on estimates from real trials and datasets. We considered three clinical areas: in vitro fertilization, severe asthma exacerbations, and acute sickle cell pain crises. We compared the two designs in terms of the expected time to complete recruitment, and the sample size recruited over a fixed recruitment period. Across the different scenarios we considered, we estimated that re-randomization could reduce the expected time to complete recruitment by between 4 and 22 months (relative reductions of 19% and 45%), or increase the sample size recruited over a fixed recruitment period by between 29% and 171%. Re-randomization can increase recruitment most for trials with a short follow-up period, a long trial recruitment duration, and patients with high rates of treatment episodes. Re-randomization has the potential to increase the recruitment rate in certain settings, and could lead to quicker and more efficient trials in these scenarios.

Smoking Cessation and Reduction in Schizophrenia (SCARIS) with e-cigarette: study protocol for a randomized control trial

PubMed Central

2014-01-01

Background It is well established in studies across several countries that tobacco smoking is more prevalent among schizophrenic patients than the general population. Electronic cigarettes are becoming increasingly popular with smokers worldwide. To date there are no large randomized trials of electronic cigarettes in schizophrenic smokers. A well-designed trial is needed to compare efficacy and safety of these products in this special population. Methods/Design Intervention: We have designed a randomized controlled trial investigating the efficacy and safety of electronic cigarette. The trial will take the form of a prospective 12-month randomized clinical study to evaluate smoking reduction, smoking abstinence and adverse events in schizophrenic smokers not intending to quit. We will also monitor quality of life, neurocognitive functioning and measure participants’ perception and satisfaction of the product. Outcome measures: A ≥50% reduction in the number of cigarettes/day from baseline, will be calculated at each study visit (“reducers”). Abstinence from smoking will be calculated at each study visit (“quitters”). Smokers who leave the study protocol before its completion and will carry out the Early Termination Visit or who will not satisfy the criteria of “reducers” and “quitters” will be defined “non responders”. Statistical analysis: The differences of continuous variables between the three groups will be evaluated with the Kruskal-Wallis Test, followed by the Dunn multiple comparison test. The differences between the three groups for normally distributed data will be evaluated with ANOVA test one way, followed by the Newman-Keuls multiple comparison test. The normality of the distribution will be evaluated with the Kolmogorov-Smirnov test. Any correlations between the variables under evaluation will be assessed by Spearman r correlation. To compare qualitative data will be used the Chi-square test. Discussion The main strengths of

Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households

PubMed Central

Cowling, Benjamin J.; Fung, Rita O. P.; Cheng, Calvin K. Y.; Fang, Vicky J.; Chan, Kwok Hung; Seto, Wing Hong; Yung, Raymond; Chiu, Billy; Lee, Paco; Uyeki, Timothy M.; Houck, Peter M.; Peiris, J. S. Malik; Leung, Gabriel M.

2008-01-01

Background There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. Methodology/Principal Findings We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. Conclusions/Significance The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. Trial Registration

A prospective cluster-randomized trial to implement the Canadian CT Head Rule in emergency departments

PubMed Central

Stiell, Ian G.; Clement, Catherine M.; Grimshaw, Jeremy M.; Brison, Robert J.; Rowe, Brian H.; Lee, Jacques S.; Shah, Amit; Brehaut, Jamie; Holroyd, Brian R.; Schull, Michael J.; McKnight, R. Douglas; Eisenhauer, Mary A.; Dreyer, Jonathan; Letovsky, Eric; Rutledge, Tim; MacPhail, Iain; Ross, Scott; Perry, Jeffrey J.; Ip, Urbain; Lesiuk, Howard; Bennett, Carol; Wells, George A.

2010-01-01

Background The Canadian CT Head Rule was developed to allow physicians to be more selective when ordering computed tomography (CT) imaging for patients with minor head injury. We sought to evaluate the effectiveness of implementing this validated decision rule at multiple emergency departments. Methods We conducted a matched-pair cluster-randomized trial that compared the outcomes of 4531 patients with minor head injury during two 12-month periods (before and after) at hospital emergency departments in Canada, six of which were randomly allocated as intervention sites and six as control sites. At the intervention sites, active strategies, including education, changes to policy and real-time reminders on radiologic requisitions were used to implement the Canadian CT Head Rule. The main outcome measure was referral for CT scan of the head. Results Baseline characteristics of patients were similar when comparing control to intervention sites. At the intervention sites, the proportion of patients referred for CT imaging increased from the “before” period (62.8%) to the “after” period (76.2%) (difference +13.3%, 95% CI 9.7%–17.0%). At the control sites, the proportion of CT imaging usage also increased, from 67.5% to 74.1% (difference +6.7%, 95% CI 2.6%–10.8%). The change in mean imaging rates from the “before” period to the “after” period for intervention versus control hospitals was not significant (p = 0.16). There were no missed brain injuries or adverse outcomes. Interpretation Our knowledge–translation-based trial of the Canadian CT Head Rule did not reduce rates of CT imaging in Canadian emergency departments. Future studies should identify strategies to deal with barriers to implementation of this decision rule and explore more effective approaches to knowledge translation. (ClinicalTrials.gov trial register no. NCT00993252) PMID:20732978

Involving patients in setting priorities for healthcare improvement: a cluster randomized trial

PubMed Central

2014-01-01

Background Patients are increasingly seen as active partners in healthcare. While patient involvement in individual clinical decisions has been extensively studied, no trial has assessed how patients can effectively be involved in collective healthcare decisions affecting the population. The goal of this study was to test the impact of involving patients in setting healthcare improvement priorities for chronic care at the community level. Methods Design: Cluster randomized controlled trial. Local communities were randomized in intervention (priority setting with patient involvement) and control sites (no patient involvement). Setting: Communities in a canadian region were required to set priorities for improving chronic disease management in primary care, from a list of 37 validated quality indicators. Intervention: Patients were consulted in writing, before participating in face-to-face deliberation with professionals. Control: Professionals established priorities among themselves, without patient involvement. Participants: A total of 172 individuals from six communities participated in the study, including 83 chronic disease patients, and 89 health professionals. Outcomes: The primary outcome was the level of agreement between patients’ and professionals’ priorities. Secondary outcomes included professionals’ intention to use the selected quality indicators, and the costs of patient involvement. Results Priorities established with patients were more aligned with core generic components of the Medical Home and Chronic Care Model, including: access to primary care, self-care support, patient participation in clinical decisions, and partnership with community organizations (p < 0.01). Priorities established by professionals alone placed more emphasis on the technical quality of single disease management. The involvement intervention fostered mutual influence between patients and professionals, which resulted in a 41% increase in agreement on common

A Data Management System Integrating Web-Based Training and Randomized Trials

ERIC Educational Resources Information Center

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D.

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance…

A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

ERIC Educational Resources Information Center

Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

2007-01-01

Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

USDA-ARS?s Scientific Manuscript database

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

PubMed Central

2010-01-01

Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p < .05) greater pain reduction. Fifty six of sixty subjects (93.3%) receiving Neuragen PN® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0%) subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601 PMID:20487567

The Sexunzipped trial: young people's views of participating in an online randomized controlled trial.

PubMed

Nicholas, Angela; Bailey, Julia V; Stevenson, Fiona; Murray, Elizabeth

2013-12-12

Incidence of sexually transmitted infections (STIs) among young people in the United Kingdom is increasing. The Internet can be a suitable medium for delivery of sexual health information and sexual health promotion, given its high usage among young people, its potential for creating a sense of anonymity, and ease of access. Online randomized controlled trials (RCTs) are increasingly being used to evaluate online interventions, but while there are many advantages to online methodologies, they can be associated with a number of problems, including poor engagement with online interventions, poor trial retention, and concerns about the validity of data collected through self-report online. We conducted an online feasibility trial that tested the effects of the Sexunzipped website for sexual health compared to an information-only website. This study reports on a qualitative evaluation of the trial procedures, describing participants' experiences and views of the Sexunzipped online trial including methods of recruitment, incentives, methods of contact, and sexual health outcome measurement. Our goal was to determine participants' views of the acceptability and validity of the online trial methodology used in the pilot RCT of the Sexunzipped intervention. We used three qualitative data sources to assess the acceptability and validity of the online pilot RCT methodology: (1) individual interviews with 22 participants from the pilot RCT, (2) 133 emails received by the trial coordinator from trial participants, and (3) 217 free-text comments from the baseline and follow-up questionnaires. Interviews were audio-recorded and transcribed verbatim. An iterative, thematic analysis of all three data sources was conducted to identify common themes related to the acceptability and feasibility of the online trial methodology. Interview participants found the trial design, including online recruitment via Facebook, online registration, email communication with the researchers, and

The Danish Cardiovascular Screening Trial (DANCAVAS): study protocol for a randomized controlled trial.

PubMed

Diederichsen, Axel Cosmus Pyndt; Rasmussen, Lars Melholt; Søgaard, Rikke; Lambrechtsen, Jess; Steffensen, Flemming Hald; Frost, Lars; Egstrup, Kenneth; Urbonaviciene, Grazina; Busk, Martin; Olsen, Michael Hecht; Mickley, Hans; Hallas, Jesper; Lindholt, Jes Sanddal

2015-12-05

The significant increase in the average life expectancy has increased the societal challenge of managing serious age-related diseases, especially cancer and cardiovascular diseases. A routine check by a general practitioner is not sufficient to detect incipient cardiovascular disease. Population-based randomized clinically controlled screening trial. 45,000 Danish men aged 65-74 years living on the Island of Funen, or in the surrounding communities of Vejle and Silkeborg. No exclusion criteria are used. One-third will be invited to cardiovascular seven-faceted screening examinations at one of four locations. The screening will include: (1) low-dose non-contrast CT scan to detect coronary artery calcification and aortic/iliac aneurysms, (2) brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension, (3) a telemetric assessment of the heart rhythm, and (4) a measurement of the cholesterol and plasma glucose levels. Up-to-date cardiovascular preventive treatment is recommended in case of positive findings. To investigate whether advanced cardiovascular screening will prevent death and cardiovascular events, and whether the possible health benefits are cost effective. Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome). Each of the 45,000 individuals is, by EPIDATA, given a random number from 1-100. Those numbered 67+ will be offered screening; the others will act as a control group. Only those randomized to the screening will be invited to the examination;the remaining participants will not. Numbers randomized: A total of 45,000 men will be randomized 1:2. Recruitment: Enrollment started October 2014. A 5% reduction in overall mortality (HR=0.95), with the risk for a type 1 error=5% and the risk for a type II error=80%, is expected. We expect a 2-year enrollment, a 10-year follow-up, and a median survival of 15 years among the controls. The attendance to screening is

Lactobacillus GG for treatment of acute childhood diarrhoea: An open labelled, randomized controlled trial

PubMed Central

Aggarwal, Sunny; Upadhyay, Amit; Shah, Dheeraj; Teotia, Neeraj; Agarwal, Astha; Jaiswal, Vijay

2014-01-01

Background & objectives: Randomized controlled trials in developed countries have reported benefits of Lactobacillus GG (LGG) in the treatment of acute watery diarrhoea, but there is paucity of such data from India. The study was aimed to evaluate the efficacy and safety of Lactobacillus GG in the treatment of acute diarrhoea in children from a semi-urban city in north India. Methods: In this open labelled, randomized controlled trial 200 children with acute watery diarrhoea, aged between 6 months to 5 years visiting outpatient department and emergency room of a teaching hospital in north India were enrolled. The children were randomized into receiving either Lactobacillus GG in dose of 10 billion cfu/day for five days or no probiotic medication in addition to standard WHO management of diarrhoea. Primary outcomes were duration of diarrhoea and time to change in consistency of stools. Results: Median (inter quartile range) duration of diarrhoea was significantly shorter in children in LGG group [60 (54-72) h vs. 78 (72-90) h; P<0.001]. Also, there was faster improvement in stool consistency in children receiving Lactobacillus GG than control group [36 (30-36) h vs. 42 (36-48) h; P<0.001]. There was significant reduction in average number of stools per day in LGG group (P<0.001) compared to the control group. These benefits were seen irrespective of rotavirus positivity in stool tests. Interpretation & conclusions: Our results showed that the use of Lactobacillus GG in children with acute diarrhoea resulted in shorter duration and faster improvement in stool consistency as compared to the control group. PMID:24820831

Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial

PubMed Central

Salehi, Zeinab; Roayaei, Mahnaz

2015-01-01

Background: Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. Methods: This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. Results: Thirty-two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after − before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after − before] of Vitamin E group = 6.37 ± 2.85, control group = 6.57 ± 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). Conclusions: The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy. PMID:26682028

Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial

PubMed Central

Little, Paul; Stuart, Beth; Wingrove, Zoe; Mullee, Mark; Thomas, Tammy; Johnson, Sophie; Leydon, Gerry; Richards-Hall, Samantha; Williamson, Ian; Yao, Lily; Zhu, Shihua; Moore, Michael

2017-01-01

BACKGROUND: Reducing the use of antibiotics for upper respiratory tract infections is needed to limit the global threat of antibiotic resistance. We estimated the effectiveness of probiotics and xylitol for the management of pharyngitis. METHODS: In this parallel-group factorial randomized controlled trial, participants in primary care (aged 3 years or older) with pharyngitis underwent randomization by nurses who provided sequential intervention packs. Pack contents for 3 kinds of material and advice were previously determined by computer-generated random numbers: no chewing gum, xylitol-based chewing gum (15% xylitol; 5 pieces daily) and sorbitol gum (5 pieces daily). Half of each group were also randomly assigned to receive either probiotic capsules (containing 24 × 109 colony-forming units of lactobacilli and bifidobacteria) or placebo. The primary outcome was mean self-reported severity of sore throat and difficulty swallowing (scale 0–6) in the first 3 days. We used multiple imputation to avoid the assumption that data were missing completely at random. RESULTS: A total of 1009 individuals consented, 934 completed the baseline assessment, and 689 provided complete data for the primary outcome. Probiotics were not effective in reducing the severity of symptoms: mean severity scores 2.75 with no probiotic and 2.78 with probiotic (adjusted difference −0.001, 95% confidence interval [CI] −0.24 to 0.24). Chewing gum was also ineffective: mean severity scores 2.73 without gum, 2.72 with sorbitol gum (adjusted difference 0.07, 95% CI −0.23 to 0.37) and 2.73 with xylitol gum (adjusted difference 0.01, 95% CI −0.29 to 0.30). None of the secondary outcomes differed significantly between groups, and no harms were reported. INTERPRETATION: Neither probiotics nor advice to chew xylitol-based chewing gum was effective for managing pharyngitis. Trial registration: ISRCTN, no. ISRCTN51472596 PMID:29255098

Improving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home

PubMed Central

2009-01-01

Background Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems. Methods/Design We have designed a randomized controlled trial to assess the effectiveness of a preventative care program delivered at home over the first 12 months of life for infants born very preterm (<30 weeks of gestational age) and their families, compared with standard medical follow-up. The aim of the program, delivered over nine sessions by a team comprising a physiotherapist and psychologist, is to improve infant development (cognitive, motor and language), behavioral regulation, caregiver-child interactions and caregiver mental health at 24 months' corrected age. The infants will be stratified by severity of brain white matter injury (assessed by magnetic resonance imaging) at term equivalent age, and then randomized. At 12 months' corrected age interim outcome measures will include motor development assessed using the Alberta Infant Motor Scale and the Neurological Sensory Motor Developmental Assessment. Caregivers will also complete a questionnaire at this time to obtain information on behavior, parenting, caregiver mental health, and social support. The primary outcomes are at 24 months' corrected age and include cognitive, motor and language development assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III). Secondary outcomes at 24 months include caregiver-child interaction measured using an observational task, and infant behavior, parenting, caregiver mental health and social support measured via standardized parental questionnaires. Discussion This paper presents the background, study design and protocol for a randomized controlled trial in very preterm infants utilizing a preventative care program

Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction (TATORT-NSTEMI): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Current guidelines recommend thrombus aspiration in patients with ST-elevation myocardial infarction (STEMI); however, there are insufficient data to unequivocally support thrombectomy in patients with non-STEMI (NSTEMI). Methods/Design The TATORT-NSTEMI (Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction) trial is a prospective, controlled, multicenter, randomized, open-label trial enrolling 460 patients. The hypothesis is that, against a background of early revascularization, adjunctive thrombectomy leads to less microvascular obstruction (MO) compared with conventional percutaneous coronary intervention (PCI) alone, as assessed by cardiac magnetic resonance imaging (CMR) in patients with NSTEMI. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary endpoint is the extent of late MO assessed by CMR. Secondary endpoints include early MO, infarct size, and myocardial salvage assessed by CMR as well as enzymatic infarct size and angiographic parameters, such as thrombolysis in myocardial infarction flow post-PCI and myocardial blush grade. Furthermore, clinical endpoints including death, myocardial re-infarction, target vessel revascularization, and new congestive heart failure will be recorded at 6 and 12 months. Safety will be assessed by the incidence of bleeding and stroke. Summary The TATORT-NSTEMI trial has been designed to test the hypothesis that thrombectomy will improve myocardial perfusion in patients with NSTEMI and relevant thrombus burden in the culprit vessel reperfused by early PCI. Trial registration The trial is registered under http://www.clinicaltrials.gov: NCT01612312. PMID:23782681

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

Literate Language Intervention with High-Need Prekindergarten Children: A Randomized Trial

ERIC Educational Resources Information Center

Phillips, Beth M.; Tabulda, Galiya; Ingrole, Smriti A.; Webb Burris, Pam; Sedgwick, T. Kayla; Chen, Shiyi

2016-01-01

Purpose: The present article reports on the implementation and results of a randomized intervention trial targeting the literate language skills of prekindergarten children without identified language disorders but with low oral language skills. Method: Children (N = 82; 45 boys and 37 girls) were screened-in and randomized to a business-as-usual…

Effect of osteopathic manipulative treatment on length of stay in a population of preterm infants: a randomized controlled trial

PubMed Central

2013-01-01

Background The use of osteopathic manipulative treatment (OMT) in preterm infants has been documented and results from previous studies suggest the association between OMT and length of stay (LOS) reduction, as well as significant improvements in several clinical outcomes. The aim of the present study is to investigate the effect of OMT on LOS in premature infants. Methods A randomized controlled trial was conducted on preterm newborns admitted to a single NICU between 2008-2009. N=110 subjects free of medical complications and with gestational age >28 and < 38 weeks were enrolled and randomized in two groups: study group (N=55) and control group (N=55). All subjects received routine pediatric care and OMT was performed to the study group for the entire period of hospitalization. Endpoints of the study included differences in LOS and daily weight gain. Results Results showed a significant association between OMT and LOS reduction (mean difference between treated and control group: -5.906; 95% C.I. -7.944, -3.869; p<0.001). OMT was not associated to any change in daily weight gain. Conclusions The present study suggests that OMT may have an important role in the management of preterm infants hospitalization. Trial registration ClinicalTrials.gov, NCT01544257. PMID:23622070

ALCOHOLIC VERSUS NONALCOHOLIC CIRRHOSIS IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY THERAPY OF BLEEDING VARICES

PubMed Central

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

Background It has been proposed that portal-systemic shunts be avoided in alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than in nonalcoholics. We examined this issue in a randomized controlled trial. Methods 211 unselected, consecutive patients with cirrhosis and bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n=106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within 8 hours. EST failure was treated by rescue PCS. 10-yr follow-up was 96%. Results Results strongly favored EPCS over EST (p<0.001). Among EPCS patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent control of bleeding 100% vs. 100%; (2) 5-yr survival 71% vs.78%; (3) encephalopathy 14% vs. 19%; (4) yearly charges $38,300 vs. $43,000. Conclusions EPCS results were similar in alcoholic and nonalcoholic cirrhotics. EPCS is an effective first line emergency treatment in all forms of cirrhosis, including alcoholic. PMID:21195430

Telephone Cognitive-Behavioral Therapy for Subthreshold Depression and Presenteeism in Workplace: A Randomized Controlled Trial

PubMed Central

Furukawa, Toshi A.; Horikoshi, Masaru; Kawakami, Norito; Kadota, Masayo; Sasaki, Megumi; Sekiya, Yuki; Hosogoshi, Hiroki; Kashimura, Masami; Asano, Kenichi; Terashima, Hitomi; Iwasa, Kazunori; Nagasaku, Minoru; Grothaus, Louis C.

2012-01-01

Background Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism). We developed a highly-structured manualized eight-session cognitive-behavioral program with a focus on subthreshold depression in the workplace and to be administered via telephone by trained psychotherapists (tCBT). Methods We conducted a parallel-group, non-blinded randomized controlled trial of tCBT in addition to the pre-existing Employee Assistance Program (EAP) versus EAP alone among workers with subthreshold depression at a large manufacturing company in Japan. The primary outcomes were depression severity as measured with Beck Depression Inventory-II (BDI-II) and presenteeism as measured with World Health Organization Health and Work Productivity Questionnaire (HPQ). In the course of the trial the follow-up period was shortened in order to increase acceptability of the study. Results The planned sample size was 108 per arm but the trial was stopped early due to low accrual. Altogether 118 subjects were randomized to tCBT+EAP (n = 58) and to EAP alone (n = 60). The BDI-II scores fell from the mean of 17.3 at baseline to 11.0 in the intervention group and to 15.7 in the control group after 4 months (p<0.001, Effect size = 0.69, 95%CI: 0.32 to 1.05). However, there was no statistically significant decrease in absolute and relative presenteeism (p = 0.44, ES = 0.15, −0.21 to 0.52, and p = 0.50, ES = 0.02, −0.34 to 0.39, respectively). Conclusion Remote CBT, including tCBT, may provide easy access to quality-assured effective psychotherapy for people in the work force who present with subthreshold depression. Further studies are needed to evaluate the effectiveness of this approach in longer terms. The study was funded by Sekisui Chemicals Co. Ltd. Trial Registration ClinicalTrials.gov NCT00885014 PMID:22532849

Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

PubMed Central

2012-01-01

Background Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services. Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. Methods/design This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve

Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

ERIC Educational Resources Information Center

Waffenschmidt, Siw; Guddat, Charlotte

2015-01-01

Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

Feasibility intervention trial of two types of improved cookstoves in three resource-limited settings: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Exposure to biomass fuel smoke is one of the leading risk factors for disease burden worldwide. International campaigns are currently promoting the widespread adoption of improved cookstoves in resource-limited settings, yet little is known about the cultural and social barriers to successful improved cookstove adoption and how these barriers affect environmental exposures and health outcomes. Design We plan to conduct a one-year crossover, feasibility intervention trial in three resource-limited settings (Kenya, Nepal and Peru). We will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site (total 120 to 138). Methods At baseline, we will collect information on sociodemographic characteristics and cooking practices, and measure respiratory health and blood pressure for all participating women. An initial observational period of four months while households use their traditional, open-fire design cookstoves will take place prior to randomization. All participants will then be randomized to receive one of two types of improved, ventilated cookstoves with a chimney: a commercially-constructed cookstove (Envirofit G3300/G3355) or a locally-constructed cookstove. After four months of observation, participants will crossover and receive the other improved cookstove design and be followed for another four months. During each of the three four-month study periods, we will collect monthly information on self-reported respiratory symptoms, cooking practices, compliance with cookstove use (intervention periods only), and measure peak expiratory flow, forced expiratory volume at 1 second, exhaled carbon monoxide and blood pressure. We will also measure pulmonary function testing in the women participants and 24-hour kitchen particulate matter and carbon monoxide levels at least once per period. Discussion Findings from this study will help us better understand the behavioral, biological, and environmental changes that occur with a cookstove

When is informed consent required in cluster randomized trials in health research?

PubMed Central

2011-01-01

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the second of the questions posed, namely, from whom, when, and how must informed consent be obtained in CRTs in health research? The ethical principle of respect for persons implies that researchers are generally obligated to obtain the informed consent of research subjects. Aspects of CRT design, including cluster randomization, cluster level interventions, and cluster size, present challenges to obtaining informed consent. Here we address five questions related to consent and CRTs: How can a study proceed if informed consent is not possible? Is consent to randomization always required? What information must be disclosed to potential subjects if their cluster has already been randomized? Is passive consent a valid substitute for informed consent? Do health professionals have a moral obligation to participate as subjects in CRTs designed to improve professional practice? We set out a framework based on the moral foundations of informed consent and international regulatory provisions to address each of these questions. First, when informed consent is not possible, a study may proceed if a research ethics committee is satisfied that conditions for a waiver of consent are satisfied. Second, informed consent to randomization may not be required if it is not possible to approach subjects at the time of randomization. Third, when potential subjects are approached after cluster randomization, they must be provided with a detailed description of the interventions in the trial arm to which their cluster has been randomized; detailed information on interventions in other trial arms need not be provided. Fourth, while passive consent may serve a variety of practical ends, it

Population screening for colorectal cancer by flexible sigmoidoscopy or CT colonography: study protocol for a multicenter randomized trial

PubMed Central

2014-01-01

Background Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. A single flexible sigmoidoscopy (FS) screening at around the age of 60 years prevents about one-third of CRC cases. However, FS screens only the distal colon, and thus mortality from proximal CRC is unaffected. Computed tomography colonography (CTC) is a highly accurate examination that allows assessment of the entire colon. However, the benefit of CTC testing as a CRC screening test is uncertain. We designed a randomized trial to compare participation rate, detection rates, and costs between CTC (with computer-aided detection) and FS as primary tests for population-based screening. Methods/Design An invitation letter to participate in a randomized screening trial comparing CTC versus FS will be mailed to a sample of 20,000 people aged 58 or 60 years, living in the Piedmont region and the Verona district of Italy. Individuals with a history of CRC, adenomas, inflammatory bowel disease, or recent colonoscopy, or with two first-degree relatives with CRC will be excluded from the study by their general practitioners. Individuals responding positively to the invitation letter will be then randomized to the intervention group (CTC) or control group (FS), and scheduled for the screening procedure. The primary outcome parameter of this part of the trial is the difference in advanced neoplasia detection between the two screening tests. Secondary outcomes are cost-effectiveness analysis, referral rates for colonoscopy induced by CTC versus FS, and the expected and perceived burden of the procedures. To compare participation rates for CTC versus FS, 2,000 additional eligible subjects will be randomly assigned to receive an invitation for screening with CTC or FS. In the CTC arm, non-responders will be offered fecal occult blood test (FOBT) as alternative screening test, while in the FS arm, non-responders will receive an invitation letter to undergo screening with either FOBT or CTC

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial

PubMed Central

Corey-Bloom, Jody; Wolfson, Tanya; Gamst, Anthony; Jin, Shelia; Marcotte, Thomas D.; Bentley, Heather; Gouaux, Ben

2012-01-01

Background: Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom. Methods: We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients’ perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue. Results: Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial. Interpretation: Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial

Improving treatment intensification to reduce cardiovascular disease risk: a cluster randomized trial

PubMed Central

2012-01-01

Background Blood pressure, lipid, and glycemic control are essential for reducing cardiovascular disease (CVD) risk. Many health care systems have successfully shifted aspects of chronic disease management, including population-based outreach programs designed to address CVD risk factor control, to non-physicians. The purpose of this study is to evaluate provision of new information to non-physician outreach teams on need for treatment intensification in patients with increased CVD risk. Methods Cluster randomized trial (July 1-December 31, 2008) in Kaiser Permanente Northern California registry of members with diabetes mellitus, prior CVD diagnoses and/or chronic kidney disease who were high-priority for treatment intensification: blood pressure ≥ 140 mmHg systolic, LDL-cholesterol ≥ 130 mg/dl, or hemoglobin A1c ≥ 9%; adherent to current medications; no recent treatment intensification). Randomization units were medical center-based outreach teams (4 intervention; 4 control). For intervention teams, priority flags for intensification were added monthly to the registry database with recommended next pharmacotherapeutic steps for each eligible patient. Control teams used the same database without this information. Outcomes included 3-month rates of treatment intensification and risk factor levels during follow-up. Results Baseline risk factor control rates were high (82-90%). In eligible patients, the intervention was associated with significantly greater 3-month intensification rates for blood pressure (34.1 vs. 30.6%) and LDL-cholesterol (28.0 vs 22.7%), but not A1c. No effects on risk factors were observed at 3 months or 12 months follow-up. Intervention teams initiated outreach for only 45-47% of high-priority patients, but also for 27-30% of lower-priority patients. Teams reported difficulties adapting prior outreach strategies to incorporate the new information. Conclusions Information enhancement did not improve risk factor control

Sensitivity analysis for missing dichotomous outcome data in multi-visit randomized clinical trial with randomization-based covariance adjustment.

PubMed

Li, Siying; Koch, Gary G; Preisser, John S; Lam, Diana; Sanchez-Kam, Matilde

2017-01-01

Dichotomous endpoints in clinical trials have only two possible outcomes, either directly or via categorization of an ordinal or continuous observation. It is common to have missing data for one or more visits during a multi-visit study. This paper presents a closed form method for sensitivity analysis of a randomized multi-visit clinical trial that possibly has missing not at random (MNAR) dichotomous data. Counts of missing data are redistributed to the favorable and unfavorable outcomes mathematically to address possibly informative missing data. Adjusted proportion estimates and their closed form covariance matrix estimates are provided. Treatment comparisons over time are addressed with Mantel-Haenszel adjustment for a stratification factor and/or randomization-based adjustment for baseline covariables. The application of such sensitivity analyses is illustrated with an example. An appendix outlines an extension of the methodology to ordinal endpoints.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

PubMed Central

Nel, Annaléne; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. Conclusions The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides. PMID

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

PubMed Central

Goldman, Mitchel P.

2017-01-01

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

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

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

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

Femoral nerve block Intervention in Neck of Femur fracture (FINOF): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Hip fractures are very painful leading to lengthy hospital stays. Conventional methods of treating pain are limited. Non-steroidal anti-inflammatories are relatively contraindicated and opioids have significant side effects.Regional anaesthesia holds promise but results from these techniques are inconsistent. Trials to date have been inconclusive with regard to which blocks to use and for how long. Interpatient variability remains a problem. Methods/Design This is a single centre study conducted at Queen’s Medical Centre, Nottingham; a large regional trauma centre in England. It is a pragmatic, parallel arm, randomized controlled trial. Sample size will be 150 participants (75 in each group). Randomization will be web-based, using computer generated concealed tables (service provided by Nottingham University Clinical Trials Unit). There is no blinding. Intervention will be a femoral nerve block (0.5 mls/kg 0.25% levo-bupivacaine) followed by ropivacaine (0.2% 5 ml/hr−1) infused via a femoral nerve catheter until 48 hours post-surgery. The control group will receive standard care. Participants will be aged over 70 years, cognitively intact (abbreviated mental score of seven or more), able to provide informed consent, and admitted directly through the Emergency Department from their place of residence. Primary outcomes will be cumulative ambulation score (from day 1 to 3 postoperatively) and cumulative dynamic pain scores (day 1 to 3 postoperatively). Secondary outcomes will be cumulative dynamic pain score preoperatively, cumulative side effects, cumulative calorific and protein intake, EUROQOL EQ-5D score, length of stay, and rehabilitation outcome (measured by mobility score). Discussion Many studies have shown the effectiveness of regional blockade in neck of femur fractures, but the techniques used have varied. This study aims to identify whether early and continuous femoral nerve block can be effective in relieving pain and enhancing mobilization.Trial

Nurse Family Partnership: Comparing Costs per Family in Randomized Trials Versus Scale-Up.

PubMed

Miller, Ted R; Hendrie, Delia

2015-12-01

The literature that addresses cost differences between randomized trials and full-scale replications is quite sparse. This paper examines how costs differed among three randomized trials and six statewide scale-ups of nurse family partnership (NFP) intensive home visitation to low income first-time mothers. A literature review provided data on pertinent trials. At our request, six well-established programs reported their total expenditures. We adjusted the costs to national prices based on mean hourly wages for registered nurses and then inflated them to 2010 dollars. A centralized data system provided utilization. Replications had fewer home visits per family than trials (25 vs. 31, p = .05), lower costs per client ($8860 vs. $12,398, p = .01), and lower costs per visit ($354 vs. $400, p = .30). Sample size limited the significance of these differences. In this type of labor intensive program, costs probably were lower in scale-up than in randomized trials. Key cost drivers were attrition and the stable caseload size possible in an ongoing program. Our estimates reveal a wide variation in cost per visit across six state programs, which suggests that those planning replications should not expect a simple rule to guide cost estimations for scale-ups. Nevertheless, NFP replications probably achieved some economies of scale.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

PubMed

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple

Generalizability of findings from randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

PubMed

Susukida, Ryoko; Crum, Rosa M; Ebnesajjad, Cyrus; Stuart, Elizabeth A; Mojtabai, Ramin

2017-07-01

To compare randomized controlled trial (RCT) sample treatment effects with the population effects of substance use disorder (SUD) treatment. Statistical weighting was used to re-compute the effects from 10 RCTs such that the participants in the trials had characteristics that resembled those of patients in the target populations. Multi-site RCTs and usual SUD treatment settings in the United States. A total of 3592 patients in 10 RCTs and 1 602 226 patients from usual SUD treatment settings between 2001 and 2009. Three outcomes of SUD treatment were examined: retention, urine toxicology and abstinence. We weighted the RCT sample treatment effects using propensity scores representing the conditional probability of participating in RCTs. Weighting the samples changed the significance of estimated sample treatment effects. Most commonly, positive effects of trials became statistically non-significant after weighting (three trials for retention and urine toxicology and one trial for abstinence); also, non-significant effects became significantly positive (one trial for abstinence) and significantly negative effects became non-significant (two trials for abstinence). There was suggestive evidence of treatment effect heterogeneity in subgroups that are under- or over-represented in the trials, some of which were consistent with the differences in average treatment effects between weighted and unweighted results. The findings of randomized controlled trials (RCTs) for substance use disorder treatment do not appear to be directly generalizable to target populations when the RCT samples do not reflect adequately the target populations and there is treatment effect heterogeneity across patient subgroups. © 2017 Society for the Study of Addiction.

Two controlled trials to increase participant retention in a randomized controlled trial of mobile phone-based smoking cessation support in the United Kingdom.

PubMed

Severi, Ettore; Free, Caroline; Knight, Rosemary; Robertson, Steven; Edwards, Philip; Hoile, Elizabeth

2011-10-01

Loss to follow-up of trial participants represents a threat to research validity. To date, interventions designed to increase participants' awareness of benefits to society of completing follow-up, and the impact of a telephone call from a senior female clinician and researcher requesting follow-up have not been evaluated robustly. Trial 1 aimed to evaluate the effect on trial follow-up of written information regarding the benefits of participation to society. Trial 2 aimed to evaluate the effect on trial follow-up of a telephone call from a senior female clinician and researcher. Two single-blind randomized controlled trials were nested within a larger trial, Txt2stop. In Trial 1, participants were allocated using minimization to receive a refrigerator magnet and a text message emphasizing the benefits to society of completing follow-up, or to a control group receiving a simple reminder regarding follow-up. In Trial 2, participants were randomly allocated to receive a telephone call from a senior female clinician and researcher, or to a control group receiving standard Txt2stop follow-up procedures. Trial 1: 33.5% (327 of 976) of the intervention group and 33.8% (329 of 974) of the control group returned the questionnaire within 26 weeks of randomization, risk ratio (RR) 0.99; 95% confidence interval (CI) 0.88-1.12. In all, 83.3% (813 of 976) of the intervention group and 82.2% (801 of/974) of the control group sent back the questionnaire within 30 weeks of randomization, RR 1.01; 95% CI 0.97, 1.05. Trial 2: 31% (20 of 65) of the intervention group and 32% (20 of 62) of the control group completed trial follow-up, RR 0.93; 95%CI 0.44, 1.98. In presence of other methods to increase follow-up neither experimental method (refrigerator magnet and text message emphasizing participation's benefits to society nor a telephone call from study's principal investigator) increased participant follow-up in the Txt2stop trial.

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

PubMed

Bello, Segun; Moustgaard, Helene; Hróbjartsson, Asbjørn

2014-10-01

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

Part versus Whole: A Randomized Trial of Central Venous Catheterization Education

ERIC Educational Resources Information Center

Chan, Angela; Singh, Sunita; Dubrowski, Adam; Pratt, Daniel D.; Zalunardo, Nadia; Nair, Parvarthy; McLaughlin, Kevin; Ma, Irene W. Y.

2015-01-01

Central venous catheterization (CVC) is a complex but commonly performed procedure. How best to teach this complex skill has not been clearly delineated. We conducted a randomized trial of the effects of two types of teaching of CVC on skill acquisition and retention. We randomly assigned novice internal medicine residents to learning CVC in-part…

Widespread sucralose exposure in a randomized clinical trial in healthy young adults12

PubMed Central

2017-01-01

Background: Low-calorie sweeteners (LCSs) are found in many foods and beverages, but consumers may not realize their presence, and their role in appetite, weight, and health is controversial. Although consumption limits based on toxicologic safety are well established, the threshold required to exert clinically relevant metabolic effects is unknown. Objectives: This study aimed to determine whether individuals who do not report consumption of LCSs can be correctly characterized as “unexposed” and to investigate whether instructions to avoid LCSs are effective in minimizing exposure. Design: Eighteen healthy 18- to 35-y-old “nonconsumers” (<1 food or beverage with LCSs/mo) enrolled in a 2-wk trial designed to evaluate the effects of LCSs on the gut microbiota. The trial consisted of 3 visits. At baseline, participants were counseled extensively about avoiding LCSs. After the run-in, participants were randomly assigned to consume diet soda containing sucralose or carbonated water (control) 3 times/d for 1 wk. Food diaries were maintained throughout the study, and a spot urine sample was collected at each visit. Results: At baseline, 8 participants had sucralose in their urine (29.9–239.0 ng/mL; mean ± SD: 111.4 ± 91.5 ng/mL). After the run-in, sucralose was found in 8 individuals (2 of whom did not have detectable sucralose at baseline) and ranged from 25.0 to 1062.0 ng/mL (mean ± SD: 191.7 ± 354.2 ng/mL). Only 1 participant reported consumption of an LCS-containing food before her visit. After the intervention, sucralose was detected in 3 individuals randomly assigned to receive carbonated water (26–121 ng/mL; mean ± SD: 60.7 ± 52.4 ng/mL). Conclusions: Despite the selection of healthy volunteers with minimal reported LCS consumption, more than one-third were exposed to sucralose at baseline and/or before randomization, and nearly half were exposed after assignment to the control. This shows that instructions to avoid LCSs are not effective and

Echocardiographic Methods, Quality Review, and Measurement Accuracy in a Randomized Multicenter Clinical Trial of Marfan Syndrome

PubMed Central

Selamet Tierney, Elif Seda; Levine, Jami C.; Chen, Shan; Bradley, Timothy J.; Pearson, Gail D.; Colan, Steven D.; Sleeper, Lynn A.; Campbell, M. Jay; Cohen, Meryl S.; Backer, Julie De; Guey, Lin T.; Heydarian, Haleh; Lai, Wyman W.; Lewin, Mark B.; Marcus, Edward; Mart, Christopher R.; Pignatelli, Ricardo H.; Printz, Beth F.; Sharkey, Angela M.; Shirali, Girish S.; Srivastava, Shubhika; Lacro, Ronald V.

2013-01-01

Background The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement. Methods Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area–adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmax Z score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process. Results Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R2 = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmax Z scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmax Z scores < 4.5. Conclusions The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility. PMID:23582510

A pilot randomized controlled trial of EKG for neonatal resuscitation

PubMed Central

Katheria, Anup; Arnell, Kathy; Brown, Melissa; Hassen, Kasim; Maldonado, Mauricio; Finer, Neil

2017-01-01

Background The seventh edition of the American Academy of Pediatrics Neonatal Resuscitation Program recommends the use of a cardiac monitor in infants that need resuscitation. Previous trials have shown that EKG heart rate is available before pulse rate from a pulse oximeter. To date no trial has looked at how the availability of electrocardiogram (EKG) affects clinical interventions in the delivery room. Objective To determine whether the availability of an EKG heart rate value and tracing to the clinical team has an effect on physiologic measures and related interventions during the stabilization of preterm infants. Design/Methods Forty (40) premature infants enrolled in a neuro-monitoring study (The Neu-Prem Trial: NCT02605733) who had an EKG monitor available were randomized to have the heart rate information from the bedside EKG monitor either displayed or not displayed to the clinical team. Heart rate, oxygen saturation, FiO2 and mean airway pressure from a data acquisition system were recorded every 2 seconds. Results were averaged over 30 seconds and the differences analyzed using two-tailed t-test. Interventions analyzed included time to first change in FiO2, first positive pressure ventilation, first increase in airway pressure, and first intubation. Results There were no significant differences in time to clinical interventions between the blinded and unblinded group, despite the unblinded group having access to a visible heart rate at 66 +/- 20 compared to 114 +/- 39 seconds for the blinded group (p < .0001). Pulse rate from oximeter was lower than EKG heart rate during the first 2 minutes of life, but this was not significant. Conclusion(s) EKG provides an earlier, and more accurate heart rate than pulse rate from an oximeter during stabilization of preterm infants, allowing earlier intervention. All interventions were started earlier in the unblinded EKG group but these numbers were not significant in this small trial. Earlier EKG placement before

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

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

Reconciling research and implementation in micro health insurance experiments in India: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Microinsurance or Community-Based Health Insurance is a promising healthcare financing mechanism, which is increasingly applied to aid rural poor persons in low-income countries. Robust empirical evidence on the causal relations between Community-Based Health Insurance and healthcare utilisation, financial protection and other areas is scarce and necessary. This paper contains a discussion of the research design of three Cluster Randomised Controlled Trials in India to measure the impact of Community-Based Health Insurance on several outcomes. Methods/Design Each trial sets up a Community-Based Health Insurance scheme among a group of micro-finance affiliate families. Villages are grouped into clusters which are congruous with pre-existing social groupings. These clusters are randomly assigned to one of three waves of implementation, ensuring the entire population is offered Community-Based Health Insurance by the end of the experiment. Each wave of treatment is preceded by a round of mixed methods evaluation, with quantitative, qualitative and spatial evidence on impact collected. Improving upon practices in published Cluster Randomised Controlled Trial literature, we detail how research design decisions have ensured that both the households offered insurance and the implementers of the Community-Based Health Insurance scheme operate in an environment replicating a non-experimental implementation. Discussion When a Cluster Randomised Controlled Trial involves randomizing within a community, generating adequate and valid conclusions requires that the research design must be made congruous with social structures within the target population, to ensure that such trials are conducted in an implementing environment which is a suitable analogue to that of a non-experimental implementing environment. PMID:21988774

Intrathecal baclofen treatment in dystonic cerebral palsy: a randomized clinical trial: the IDYS trial

PubMed Central

2013-01-01

Background Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex. The daily care of these patients can be difficult due to dystonic movements. Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice. Despite this widespread adoption, high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospective data are needed to judge the usefulness and indications for dystonic cerebral palsy. The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients. Furthermore, we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient. Methods/Design A double blind placebo-controlled multi-center randomized clinical trial will be performed in 30 children with dystonic cerebral palsy. Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy, Gross Motor Functioning Classification System level IV or V, with lesions in the cerebral white matter, basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included. Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment, both via an implanted pump. After this three month period, all patients will receive intrathecal baclofen treatment, with a follow-up after nine months. The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling. Secondary outcome measurements on the level of body functions include dystonia, spasticity, pain, comfort and sleep-related breathing disorders. Side effects will be monitored and we will study whether patient characteristics

Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor.

PubMed

Flacco, Maria Elena; Manzoli, Lamberto; Boccia, Stefania; Capasso, Lorenzo; Aleksovska, Katina; Rosso, Annalisa; Scaioli, Giacomo; De Vito, Corrado; Siliquini, Roberta; Villari, Paolo; Ioannidis, John P A

2015-07-01

To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A Randomized Trial of Heart Failure Disease Management in Skilled Nursing Facilities: Design and Rationale

PubMed Central

Boxer, Rebecca S.; Dolansky, Mary A.; Bodnar, Christine A.; Singer, Mendel E.; Albert, Jeffery M.; Gravenstein, Stefan

2013-01-01

Background Heart failure disease management can improve health outcomes for older community dwelling patients with heart failure. Heart failure disease management has not been studied in skilled nursing facilities, a major site of transitional care for older adults. Methods and Anticipated Results The objective of this trial is to investigate if a heart failure disease management program (HF-DMP) in skilled nursing facilities (SNF) will decrease all-cause rehospitalizations for the first 60 days post SNF admission. The trial is a randomized cluster trial to be conducted in 12 for-profit SNF in the greater Cleveland area. The study population is inclusive of patients with heart failure regardless of ejection fraction but excludes those patients on dialysis and with a life expectancy of 6 months or less. The HF-DMP includes 7 elements considered standard of care for patients with heart failure: documentation of left ventricular function, tracking of weight and symptoms, medication titration, discharge instructions, 7 day follow up appointment post SNF discharge, patient education. The HF-DMP is conducted by a research nurse tasked with adhering to each element of the program and regularly audited to maintain fidelity of the program. Additional outcomes include health status, self-care management, and discharge destination. Conclusion The SNF-Connect Trial is the first trial of its kind to assess if a HF-DMP will improve outcomes for patients in SNFs. This trial will provide evidence on the effectiveness of HF-DMP to improve outcomes for older frail heart failure patients undergoing post-acute rehabilitation. PMID:23871475

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

PubMed Central

Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G

2008-01-01

Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713 PMID:18503714

Guidelines for randomized clinical trial protocol content: a systematic review

PubMed Central

2012-01-01

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

Methods for synthesizing findings on moderation effects across multiple randomized trials.

PubMed

Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2013-04-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design.

Vilazodone for Cannabis Dependence: A Randomized, Controlled Pilot Trial

PubMed Central

McRae-Clark, Aimee L.; Baker, Nathaniel L.; Gray, Kevin M.; Killeen, Therese; Hartwell, Karen J.; Simonian, Susan J.

2016-01-01

Background and Objectives The purpose of this study was to evaluate the efficacy of vilazodone, a selective serotonin receptor inhibitor and partial 5-HT1A agonist, for treatment of cannabis dependence. Methods Seventy-six cannabis-dependent adults were randomized to receive either up to 40 mg/day of vilazodone (n=41) or placebo (n=35) for eight weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests; secondary outcomes included cannabis use self-report and cannabis craving. Results Participants in both groups reported reduced self-reported cannabis use over the course of the study; however, vilazodone provided no advantage over placebo in reducing cannabis use. Men had significantly lower creatinine-adjusted cannabinoid levels and a trend for increased negative urine cannabinoid tests than women. Discussion and Conclusions Vilazodone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes than men. Scientific Significance Further medication development efforts for cannabis use disorders are needed, and gender should be considered as an important variable in future trials. PMID:26685701

Design and analysis of group-randomized trials in cancer: A review of current practices.

PubMed

Murray, David M; Pals, Sherri L; George, Stephanie M; Kuzmichev, Andrey; Lai, Gabriel Y; Lee, Jocelyn A; Myles, Ranell L; Nelson, Shakira M

2018-06-01

The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues. Published by Elsevier Inc.

Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial

PubMed Central

2011-01-01

Background The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions. Methods Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome. Results Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity. Conclusion A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings. Trial registration ClinicalTrials.gov NCT00507988 PMID:21527028

Clinic Versus Online Social Network–Delivered Lifestyle Interventions: Protocol for the Get Social Noninferiority Randomized Controlled Trial

PubMed Central

Wang, Monica L; Waring, Molly E; Jake-Schoffman, Danielle E; Oleski, Jessica L; Michaels, Zachary; Goetz, Jared M; Lemon, Stephenie C; Ma, Yunsheng

2017-01-01

Background Online social networks may be a promising modality to deliver lifestyle interventions by reducing cost and burden. Although online social networks have been integrated as one component of multimodality lifestyle interventions, no randomized trials to date have compared a lifestyle intervention delivered entirely via online social network with a traditional clinic-delivered intervention. Objective This paper describes the design and methods of a noninferiority randomized controlled trial, testing (1) whether a lifestyle intervention delivered entirely through an online social network would produce weight loss that would not be appreciably worse than that induced by a traditional clinic-based lifestyle intervention among overweight and obese adults and (2) whether the former would do so at a lower cost. Methods Adults with body mass index (BMI) between 27 and 45 kg/m2 (N=328) will be recruited from the communities in central Massachusetts. These overweight or obese adults will be randomized to two conditions: a lifestyle intervention delivered entirely via the online social network Twitter (Get Social condition) and an in-person group-based lifestyle intervention (Traditional condition) among overweight and obese adults. Measures will be obtained at baseline, 6 months, and 12 months after randomization. The primary noninferiority outcome is percentage weight loss at 12 months. Secondary noninferiority outcomes include dietary intake and moderate intensity physical activity at 12 months. Our secondary aim is to compare the conditions on cost. Exploratory outcomes include treatment retention, acceptability, and burden. Finally, we will explore predictors of weight loss in the online social network condition. Results The final wave of data collection is expected to conclude in June 2019. Data analysis will take place in the months following and is expected to be complete in September 2019. Conclusions Findings will extend the literature by revealing whether

Snoezelen Room and Childbirth Outcome: A Randomized Clinical Trial

PubMed Central

Jamshidi Manesh, Mansoureh; Kalati, Mahnaz; Hosseini, Fatemeh

2015-01-01

Background: One of the strategies for a good outcome and pain free childbearing is to design the delivery room. Objectives: The aim of this study was to evaluate the effects of snoezelen room on childbearing outcome such as pain intensity, duration of labor, and perinea status in nulliparous women. Patients and Methods: This study was a randomized controlled clinical trial consists of 100 childbearing women. They were randomly divided into 2 groups. The experimental group went to snoezelen room when their cervix dilation was 4 cm, while the control group went to physiologic delivery room with the same cervix dilation. Results: The mean ± SD of VAS (Visual Analogue Scale) pain intensity of the experimental and control groups before the intervention were 5.1 ± 1.95 and 5.58 ± 1.62, respectively (P = 0.13). The mean ± SD of VAS pain intensity scores of the experimental and control groups after 3 hours spending in their assigned rooms were 5.26 ± 0.86 and 9.56 ± 1.48, respectively (P = 0.01). The mean ± SD of the first stage scores of the experimental and control groups were 6.95 ± 0.97 and 8.41 ± 0.67, respectively (P = 0.042). About 92% of participants’ intervention vs. 66% of control participants had perinea laceration (P = 0.041). Conclusions: According to the findings of the present study, distracting senses in snoezelen room decreases mother’s pain intensity, the length of labor, and incidence of episiotomy. PMID:26082849

Effect of electroacupuncture in postanesthetic shivering during regional anesthesia: a randomized controlled trial

PubMed Central

2012-01-01

Background Shivering during regional anesthesia is a common complication and is related to a decrease in the patient’s core body temperature. Previous studies have shown that acupuncture on specific acupoints can preserve core body temperature. The present study evaluated the effect of electroacupuncture in preventing the shivering caused by regional anesthesia. Methods This prospective and randomized controlled study analyzed the data from 80 patients undergoing urological surgery, who were classified as ASA I or II. Spinal anesthesia was performed in all patients using 15 mg of bupivacaine. The patients were randomly allocated to receive either placebo acupuncture (Group P, n = 40) or electroacupuncture (Group A, n = 40) for 30 min before administration of spinal anesthesia. Shivering score was recorded at 5 min intervals, with 0 representing no shivering and 4 representing the most severe shivering possible. Heart rate, blood pressure, and tympanic temperature were recorded before the intrathecal injection, and again every 5 min thereafter until 30 min. Results After spinal anesthesia, the decrease in tympanic temperature was less for Group A patients than Group P, with the difference being statistically significant. After 15 min, 13 patients in Group P attained a shivering score of 3 or more, compared with 3 patients in Group A. Significantly more patients in Group P attained a shivering score of at least 1. Conclusions The prophylactic use of electroacupuncture might maintain core body temperature, and may effectively prevent the shivering that commonly develops during regional anesthesia. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12612000096853. PMID:23181618

Engineering Online and In-person Social Networks for Physical Activity: A Randomized Trial

PubMed Central

Rovniak, Liza S.; Kong, Lan; Hovell, Melbourne F.; Ding, Ding; Sallis, James F.; Ray, Chester A.; Kraschnewski, Jennifer L.; Matthews, Stephen A.; Kiser, Elizabeth; Chinchilli, Vernon M.; George, Daniel R.; Sciamanna, Christopher N.

2016-01-01

Background Social networks can influence physical activity, but little is known about how best to engineer online and in-person social networks to increase activity. Purpose To conduct a randomized trial based on the Social Networks for Activity Promotion model to assess the incremental contributions of different procedures for building social networks on objectively-measured outcomes. Methods Physically inactive adults (n = 308, age, 50.3 (SD = 8.3) years, 38.3% male, 83.4% overweight/obese) were randomized to 1 of 3 groups. The Promotion group evaluated the effects of weekly emailed tips emphasizing social network interactions for walking (e.g., encouragement, informational support); the Activity group evaluated the incremental effect of adding an evidence-based online fitness walking intervention to the weekly tips; and the Social Networks group evaluated the additional incremental effect of providing access to an online networking site for walking, and prompting walking/activity across diverse settings. The primary outcome was mean change in accelerometer-measured moderate-to-vigorous physical activity (MVPA), assessed at 3 and 9 months from baseline. Results Participants increased their MVPA by 21.0 mins/week, 95% CI [5.9, 36.1], p = .005, at 3 months, and this change was sustained at 9 months, with no between-group differences. Conclusions Although the structure of procedures for targeting social networks varied across intervention groups, the functional effect of these procedures on physical activity was similar. Future research should evaluate if more powerful reinforcers improve the effects of social network interventions. Trial Registration Number NCT01142804 PMID:27405724

The handsearching of 2 medical journals of Bahrain for reports of randomized controlled trials.

PubMed

Al-Hajeri, Amani A; Fedorowicz, Zbigniew; Amin, Fawzi A; Eisinga, Anne

2006-04-01

To identify reports of randomized trials by handsearching 2 Bahrain medical journals, which are indexed in the biomedical database EMBASE and to determine any added value of the handsearching by comparing the reports found by handsearching with what would have been found by searching EMBASE to examine (i) the precision and sensitivity of the EMBASE index term Randomized Controlled Trial (RCT) and (ii) The Cochrane Collaboration's systematic electronic search of EMBASE (which uses 4 index terms and 9 free-text terms). All issues of the Bahrain Medical Bulletin (BMB) (1979-2004) and the Journal of the Bahrain Medical Society (JBMS) (1989-2004) were handsearched in February 2005 for reports of RCTs or Controlled Clinical Trials (CCTs), according to Cochrane eligibility criteria. Out of 395 articles in BMB we found reports of 12 RCTs and 4 CCTs. Distribution by country of corresponding author: Jordan (4 RCTs, one CCT), Bahrain (one RCT, one CCT), India (3 RCTs, one CCT), Kuwait (one CCT), Saudi Arabia (2 RCTs), USA/Bahrain (one RCT), and Oman (one RCT); and by specialty: Anesthesia (8), Surgery (1) Pediatrics (1), Radiotherapy (1), Community Medicine (1), Sports Medicine (1), Obstetrics/Gynecology (3). The Journal of the Bahrain Medical Society included reports of 14 RCTs and 3 CCTs, out of 97 articles. Distribution by country of corresponding author: Jordan (9 RCTs, 2 CCTs), Bahrain (3 RCTs), Egypt (one RCT), Kuwait (one RCT), and Saudi Arabia (one RCT); and by specialty: Anesthesia (7), General Surgery (3), Obstetrics/Gynecology (1), Radiotherapy (1), Pediatrics (1), Orthopaedic Surgery (1), Education (1) Ear Nose and Throat (1) Ophthalmology (1). Overall, of the 33 reports of trials found by handsearching both journals, only 23 were included in EMBASE of which only 6 had been indexed with the term RCT. Of the 23 reports of trials included in EMBASE, 16 had been identified in the Collaboration s systematic search of EMBASE. Two reports of trials could have been

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

PubMed Central

2013-01-01