Pilot Study of Treatment for Major Depression Among Women Prisoners with Substance Use Disorder

PubMed Central

Johnson, Jennifer E.; Zlotnick, Caron

2012-01-01

This study, the largest randomized controlled trial of treatment for major depressive disorder (MDD) in an incarcerated population to date, wave-randomized 38 incarcerated women (6 waves) in prison substance use treatment with MDD to group interpersonal psychotherapy (IPT) or to an attention-matched control. Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants. Control participants improved later, after prison release. IPT's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD. PMID:22694906

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting

PubMed Central

Wang, Ruibin; Prasad, Vinay; Bates, Susan E.; Fojo, Tito

2016-01-01

Background. Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Materials and Methods. Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4−6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. Results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11–1.36], p < .001; and 1.64 [1.15–2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38–1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61–1.29]; p = .532). Conclusion. This is the largest reported study examining why oncology trials are not published. The data show that 4−6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. Implications for Practice: The Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects notes the ethical obligation to report clinical trial data, whether positive or negative. This obligation is listed alongside requirements for risk minimization, access, confidentiality, and informed consent, all bedrocks of the clinical trial system, yet clinical trials are often not published, particularly if negative or difficult to complete. This study found that among American Society for Clinical Oncology (ASCO) Annual Meeting abstracts, 2009–2011, only 61% were published 4–6 years later: 75% of randomized trials and 54% of nonrandomized trials. Clinicians need to insist that every study in which they participate is published. PMID:26888691

Can Using Rigorous Evidence to Guide Federal Education Funds Improve Student Achievement? Randomized Trials Show Encouraging Initial Results for DoED's Investing in Innovation Fund

ERIC Educational Resources Information Center

Coalition for Evidence-Based Policy, 2014

2014-01-01

An important recent development in evidence-based policy is the federal government's use of a "tiered evidence" approach to allocating funding in grant programs such as the U.S. Department of Education's Investing in Innovation Fund (i3). A central feature of this approach is that the largest grants are awarded to fund large-scale…

To What Extent Do Head Start's Effects on Children's Language, Literacy, Mathematics, and Socio-Emotional Skills Vary across Individuals, Subgroups, and Centers?

ERIC Educational Resources Information Center

Bloom, Howard S.; Weiland, Christina

2014-01-01

Head Start is the largest publicly funded preschool program in the U.S., and one of its primary goals is to improve the school readiness of low-income children. As has been widely reported, the first randomized trial of Head Start in the program's history found some evidence that it is achieving this goal. Receiving one year of Head Start had…

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

PubMed

Kasner, Scott E; Lavados, Pablo; Sharma, Mukul; Wang, Yongjun; Wang, Yilong; Dávalos, Antoni; Shamalov, Nikolay; Cunha, Luis; Lindgren, Arne; Mikulik, Robert; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens; Amarenco, Pierre; Ameriso, Sebastián F; Tatlisumak, Turgut; Veltkamp, Roland; Hankey, Graeme J; Toni, Danilo S; Bereczki, Daniel; Uchiyama, Shinichiro; Ntaios, George; Yoon, Byung-Woo; Brouns, Raf; DeVries Basson, M M; Endres, Matthias; Muir, Keith; Bornstein, Natan; Ozturk, Serefnur; O'Donnell, Martin; Mundl, Hardi; Pater, Calin; Weitz, Jeffrey; Peacock, W Frank; Swaminathan, Balakumar; Kirsch, Bodo; Berkowitz, Scott D; Peters, Gary; Pare, Guillaume; Themeles, Ellison; Shoamanesh, Ashkan; Connolly, Stuart J; Hart, Robert G

2018-06-01

The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

PubMed Central

Antman, Karen

2002-01-01

High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival. PMID:12053718

Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

PubMed

Antman, Karen

2002-01-01

High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival.

Rationale, design, and baseline characteristics of the Acetylcystein for Contrast-Induced nephropaThy (ACT) Trial: a pragmatic randomized controlled trial to evaluate the efficacy of acetylcysteine for the prevention of contrast-induced nephropathy

PubMed Central

2009-01-01

Background Aceltylcysteine has been evaluated in several small trials as a means of reducing the risk of contrast-induced nephropathy (CIN), however systematic reviews of these studies do not provide conclusive answers. Therefore, a large randomized controlled trial (RCT) is needed to provide a reliable answer as to whether acetylcysteine is effective in decreasing the risk of CIN in high-risk patients undergoing angiographic procedures. Methods ACT is a RCT of acetylcysteine versus placebo in 2,300 patients at-risk for CIN undergoing an intravascular angiographic procedure. The randomization list will be concealed. Participants, health care staff, investigators and outcome assessors will be blinded to whether patients receive acetylcysteine or placebo. All analysis will follow the intention-to-treat principle. The study drugs (acetylcysteine 1200 mg or placebo) will be administered orally twice daily for two doses before and two doses after the procedure. The primary outcome is the occurrence of CIN, defined as a 25% elevation of serum creatinine above baseline between 48 and 96 hours after angiography. Discussion The first patient entered the trial on September, 2008. Up to April 7, 2009, 810 patients had been included in 35 centers. The mean age was 69 (Standard deviation: 10), 18% had a baseline serum creatinine >1.5 mg/dL, 57% were diabetics and 13% had a history of heart failure. The ongoing ACT Trial is the largest multicentre RCT that will determine whether acetylcysteine is effective in decreasing the risk of CIN in patients at risk undergoing angiography. Trial registration Clinicaltrials.gov NCT00736866 PMID:19497091

Six-day randomized safety trial of intravaginal lime juice.

PubMed

Mauck, Christine K; Ballagh, Susan A; Creinin, Mitchell D; Weiner, Debra H; Doncel, Gustavo F; Fichorova, Raina N; Schwartz, Jill L; Chandra, Neelima; Callahan, Marianne M

2008-11-01

Nigerian women reportedly apply lime juice intravaginally to protect themselves against HIV. In vitro data suggest that lime juice is virucidal, but only at cytotoxic concentrations. This is the first controlled, randomized safety trial of lime juice applied to the human vagina. Forty-seven women were randomized to apply water or lime juice (25%, 50%, or undiluted) intravaginally twice daily for two 6-day intervals, separated by a 3-week washout period. Product application also was randomized: during 1 interval, product was applied using a saturated tampon and in the other by douche. Vaginal pH, symptoms, signs of irritation observed via naked eye examination and colposcopy, microflora, and markers of inflammation in cervicovaginal lavages were evaluated after 1 hour and on days 3 and 7. The largest reduction in pH was about one-half a pH unit, seen 1 hour after douching with 100% lime juice. We observed a dose-dependent pattern of symptoms and clinical and laboratory findings that were consistent with a compromised vaginal barrier function. The brief reduction in pH after vaginal lime juice application is unlikely to be virucidal in the presence of semen. Lime juice is unlikely to protect against HIV and may actually be harmful.

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial.

PubMed

Friedli, Karin; Guirguis, Ayman; Almond, Michael; Day, Clara; Chilcot, Joseph; Da Silva-Gane, Maria; Davenport, Andrew; Fineberg, Naomi A; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2017-02-07

Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants. Copyright © 2017 by the American Society of Nephrology.

Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels.

PubMed

Casali, Paolo G; Zalcberg, John; Le Cesne, Axel; Reichardt, Peter; Blay, Jean-Yves; Lindner, Lars H; Judson, Ian R; Schöffski, Patrick; Leyvraz, Serge; Italiano, Antoine; Grünwald, Viktor; Pousa, Antonio Lopez; Kotasek, Dusan; Sleijfer, Stefan; Kerst, Jan M; Rutkowski, Piotr; Fumagalli, Elena; Hogendoorn, Pancras; Litière, Saskia; Marreaud, Sandrine; van der Graaf, Winette; Gronchi, Alessandro; Verweij, Jaap

2017-05-20

Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-year overall survival rates were 19.4% and 21.5%, respectively. At multivariable analysis, age (< 60 years), performance status (0 v ≥ 1), size of the largest lesion (smaller), and KIT mutation (exon 11) were significant prognostic factors for the probability of surviving beyond 10 years. Conclusion This trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.

Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.

PubMed

Gibbons, Robert D; Hur, Kwan; Brown, C Hendricks; Davis, John M; Mann, J John

2012-06-01

Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression. To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations. Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine. Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction. To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.

Does Encouragement Matter in Improving Gender Imbalances in Technical Fields? Evidence from a Randomized Controlled Trial

PubMed Central

Unkovic, Cait; Sen, Maya; Quinn, Kevin M.

2016-01-01

Does encouragement help address gender imbalances in technical fields? We present the results of one of the first and largest randomized controlled trials on the topic. Using an applied statistics conference in the social sciences as our context, we randomly assigned half of a pool of 3,945 graduate students to receive two personalized emails encouraging them to apply (n = 1,976) and the other half to receive nothing (n = 1,969). We find a robust, positive effect associated with this simple intervention and suggestive evidence that women responded more strongly than men. However, we find that women’s conference acceptance rates are higher within the control group than in the treated group. This is not the case for men. The reason appears to be that female applicants in the treated group solicited supporting letters at lower rates. Our findings therefore suggest that “low dose” interventions may promote diversity in STEM fields but may also have the potential to expose underlying disparities when used alone or in a non-targeted way. PMID:27097315

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

The effect of prolonged and exclusive breast-feeding on dental caries in early school-age children. New evidence from a large randomized trial.

PubMed

Kramer, M S; Vanilovich, I; Matush, L; Bogdanovich, N; Zhang, X; Shishko, G; Muller-Bolla, M; Platt, R W

2007-01-01

To study the effects of prolonged and exclusive breast-feeding on dental caries, we followed up children participating in the Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy, mother-infant breast-feeding pairs were enrolled from 31 Belarussian maternity hospitals and affiliated polyclinics, of whom 13,889 (81.5%) were followed up at 6.5 years. At follow-up, polyclinic pediatricians transcribed the reports of a standard dental examination performed by public health dentists at age 6 years and recorded in the children's polyclinic charts. Analysis was based on intention to treat, with a statistical model that accounts for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 months (43.3 vs. 6.4%, p < 0.001) and a significantly higher prevalence of any breast-feeding at all ages up to and including 12 months. No significant intervention effects were observed on dental caries. Our results, based on the largest randomized trial ever conducted in the area of human lactation, provide no evidence of beneficial or harmful effects of prolonged and exclusive breast-feeding on dental caries at early school age. (c) 2007 S. Karger AG, Basel

Use of ClinicalTrials.gov to estimate condition-specific nocebo effects and other factors affecting outcomes of analgesic trials.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

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 pregnancy. Trial registration ISRCTN48600346 PMID:23035669

Doppler-guided haemorrhoidal artery ligation with suture mucopexy compared with suture mucopexy alone for the treatment of Grade III haemorrhoids: a prospective randomized controlled trial.

PubMed

Aigner, F; Kronberger, I; Oberwalder, M; Loizides, A; Ulmer, H; Gruber, L; Pratschke, J; Peer, S; Gruber, H

2016-07-01

Novel minimally invasive techniques aimed to reposition the haemorrhoidal zone have been established for prolapsing haemorrhoids. We present a prospective randomized controlled trial to evaluate the efficacy of additional Doppler-guided ligation of submucosal haemorrhoidal arteries (DG-HAL) in patients with symptomatic Grade III haemorrhoids. The trial was registered as ClinicalTrials.gov identifier NCT02372981. All consecutive patients with symptomatic Grade III haemorrhoids were randomly allocated to one of the two study arms: (i) Group A, DG-HAL with mucopexy or (ii) Group B, mucopexy alone. End-points were postoperative pain, faecal incontinence, bleeding, residual prolapse and alterations of the vascularization of the anorectal vascular plexus. Vascularization of the anorectal vascular plexus was assessed by transperineal contrast enhanced ultrasound. Patients recorded their symptoms in a diary maintained for a month. Forty patients were recruited and randomized to the two study groups. Patients in Group A had less pain in the first two postoperative weeks. At the 12-month follow-up, two patients in Group A (10%) and one in Group B (5%) showed recurrent Grade III haemorrhoids (P = 0.274). No significant morphological changes were observed in the transperineal ultrasound findings between the preoperative assessment and the assessment at 1 and 6 months in either group (P > 0.05). Mucopexy techniques for treating prolapsing haemorrhoids are effective, but DG-HAL does not add significantly to the results achieved by mucopexy. Repositioning the haemorrhoidal zone is the key to success, and mucopexy should be placed at the sites of the largest visible prolapse. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Three Months of Progressive High-Load Versus Traditional Low-Load Strength Training Among Patients With Rotator Cuff Tendinopathy: Primary Results From the Double-Blind Randomized Controlled RoCTEx Trial.

PubMed

Ingwersen, Kim Gordon; Jensen, Steen Lund; Sørensen, Lilli; Jørgensen, Hans Ri; Christensen, Robin; Søgaard, Karen; Juul-Kristensen, Birgit

2017-08-01

Progressive high-load exercise (PHLE) has led to positive clinical results in patients with patellar and Achilles tendinopathy. However, its effects on rotator cuff tendinopathy still need to be investigated. To assess the clinical effects of PHLE versus low-load exercise (LLE) among patients with rotator cuff tendinopathy. Randomized controlled trial; Level of evidence, 1. Patients with rotator cuff tendinopathy were recruited and randomized to 12 weeks of PHLE or LLE, stratified for concomitant administration of corticosteroid injection. The primary outcome measure was change from baseline to 12 weeks in the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, assessed in the intention-to-treat population. A total of 100 patients were randomized to PHLE (n = 49) or LLE (n = 51). Mean changes in the DASH questionnaire were 7.11 points (95% CI, 3.07-11.16) and 8.39 points (95% CI, 4.35-12.44) in the PHLE and LLE groups, respectively; this corresponded to a statistically nonsignificant adjusted mean group difference of -1.37 points (95% CI, -6.72 to 3.99; P = .61). Similar nonsignificant results were seen for pain, range of motion, and strength. However, a significant interaction effect was found between the 2 groups and concomitant corticosteroid use ( P = .028), with the largest positive change in DASH in favor of PHLE for the group receiving concomitant corticosteroid. The study results showed no superior benefit from PHLE over traditional LLE among patients with rotator cuff tendinopathy. Further investigation of the possible interaction between exercise type and corticosteroid injection is needed to establish optimal and potentially synergistic combinations of these 2 factors. NCT01984203 (ClinicalTrials.gov identifier): Rotator Cuff Tendinopathy Exercise Trial (RoCTEx).

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols

PubMed Central

Mhaskar, Rahul; Djulbegovic, Benjamin; Magazin, Anja; Soares, Heloisa P.; Kumar, Ambuj

2011-01-01

Objectives To assess whether reported methodological quality of randomized controlled trials (RCTs) reflect the actual methodological quality, and to evaluate the association of effect size (ES) and sample size with methodological quality. Study design Systematic review Setting Retrospective analysis of all consecutive phase III RCTs published by 8 National Cancer Institute Cooperative Groups until year 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study. Results 429 RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94, 95%CI: 0.88, 0.99) and 24% (RHR: 1.24, 95%CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality. Conclusion The largest study to-date shows poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results. PMID:22424985

Zero-inflated count models for longitudinal measurements with heterogeneous random effects.

PubMed

Zhu, Huirong; Luo, Sheng; DeSantis, Stacia M

2017-08-01

Longitudinal zero-inflated count data arise frequently in substance use research when assessing the effects of behavioral and pharmacological interventions. Zero-inflated count models (e.g. zero-inflated Poisson or zero-inflated negative binomial) with random effects have been developed to analyze this type of data. In random effects zero-inflated count models, the random effects covariance matrix is typically assumed to be homogeneous (constant across subjects). However, in many situations this matrix may be heterogeneous (differ by measured covariates). In this paper, we extend zero-inflated count models to account for random effects heterogeneity by modeling their variance as a function of covariates. We show via simulation that ignoring intervention and covariate-specific heterogeneity can produce biased estimates of covariate and random effect estimates. Moreover, those biased estimates can be rectified by correctly modeling the random effects covariance structure. The methodological development is motivated by and applied to the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study, the largest clinical trial of alcohol dependence performed in United States with 1383 individuals.

Music in mind, a randomized controlled trial of music therapy for young people with behavioural and emotional problems: study protocol.

PubMed

Porter, Sam; Holmes, Valerie; McLaughlin, Katrina; Lynn, Fiona; Cardwell, Chris; Braiden, Hannah-Jane; Doran, Jackie; Rogan, Sheelagh

2012-10-01

This article is a report of a trial protocol to determine if improvizational music therapy leads to clinically significant improvement in communication and interaction skills for young people experiencing social, emotional or behavioural problems. Music therapy is often considered an effective intervention for young people experiencing social, emotional or behavioural difficulties. However, this assumption lacks empirical evidence. Music in mind is a multi-centred single-blind randomized controlled trial involving 200 young people (aged 8-16 years) and their parents. Eligible participants will have a working diagnosis within the ambit of international classification of disease 10 mental and behavioural disorders and will be recruited over 15 months from six centres within the Child and Adolescent Mental Health Services of a large health and social care trust in Northern Ireland. Participants will be randomly allocated in a 1:1 ratio to receive standard care alone or standard care plus 12 weekly music therapy sessions delivered by the Northern Ireland Music Therapy Trust. Baseline data will be collected from young people and their parents using standardized outcome measures for communicative and interaction skills (primary endpoint), self-esteem, social functioning, depression and family functioning. Follow-up data will be collected 1 and 13 weeks after the final music therapy session. A cost-effectiveness analysis will also be carried out. This study will be the largest trial to date examining the effect of music therapy on young people experiencing social, emotional or behavioural difficulties and will provide empirical evidence for the use of music therapy among this population. Trial registration. This study is registered in the ISRCTN Register, ISRCTN96352204. Ethical approval was gained in October 2010. © 2012 Blackwell Publishing Ltd.

The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.

PubMed

Ahmad, Zafar; Brooks, Roger; Kang, Sertaz-Niel; Weaver, Holly; Nunney, Ian; Tytherleigh-Strong, Graham; Rushton, Neil

2013-11-01

To evaluate the evidence for application of platelet-rich plasma (PRP) in lateral epicondylitis. We carried out a systematic review of the current evidence on the effects of PRP in lateral epicondylitis on clinical outcomes. We performed a comprehensive search of the PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases using various combinations of the commercial names of each PRP preparation and "lateral epicondylitis" (with its associated terms), looking specifically at human studies. Data validity was assessed and collected on clinical outcome. Nine studies met the inclusion criteria, of which 5 were randomized controlled trials. Two cohort studies showed that PRP improved clinical satisfaction scores. One case-control study showed that PRP yielded a significantly greater improvement in symptoms compared with bupivacaine. Two randomized controlled trials compared the effect of injections of PRP and blood. Only 1 of the studies noted a significant difference at the 6-week time point. Three randomized controlled trials compared corticosteroids with PRP. Two of the smaller trials, which had follow-up periods of 6 weeks and 3 months, showed no significant difference between treatment groups. The largest randomized controlled trial found that PRP had significant benefit compared with corticosteroids with regard to pain and Disabilities of the Arm, Shoulder and Hand scores at 1- and 2-year time points. This review highlights the limited but evolving evidence for the use of PRP in lateral epicondylitis; however, further research is required to understand the concentration and preparation that facilitate the best clinical outcome. Characterizing the timing of the intervention would optimize the health economics behind the decision to treat for the patient and health care provider. Level III, systematic review of Level I to III studies. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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

PubMed

Ussher, Michael; Aveyard, Paul; Manyonda, Isaac; Lewis, Sarah; West, Robert; Lewis, Beth; Marcus, Bess; Taylor, Adrian H; Barton, Pelham; Coleman, Tim

2012-10-04

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. 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. This trial will assess whether a PA intervention is effective when used for smoking cessation during pregnancy. ISRCTN48600346.

Maximizing Effectiveness Trials in PTSD and SUD Through Secondary Analysis: Benefits and Limitations Using the National Institute on Drug Abuse Clinical Trials Network "Women and Trauma" Study as a Case Example.

PubMed

Hien, Denise A; Campbell, Aimee N C; Ruglass, Lesia M; Saavedra, Lissette; Mathews, Abigail G; Kiriakos, Grace; Morgan-Lopez, Antonio

2015-09-01

Recent federal legislation and a renewed focus on integrative care models underscore the need for economical, effective, and science-based behavioral health care treatment. As such, maximizing the impact and reach of treatment research is of great concern. Behavioral health issues, including the frequent co-occurrence of substance use disorders (SUD) and posttraumatic stress disorder (PTSD), are often complex, with a myriad of factors contributing to the success of interventions. Although treatment guides for comorbid SUD/PTSD exist, most patients continue to suffer symptoms following the prescribed treatment course. Further, the study of efficacious treatments has been hampered by methodological challenges (e.g., overreliance on "superiority" designs (i.e., designs structured to test whether or not one treatment statistically surpasses another in terms of effect sizes) and short term interventions). Secondary analyses of randomized controlled clinical trials offer potential benefits to enhance understanding of findings and increase the personalization of treatment. This paper offers a description of the limits of randomized controlled trials as related to SUD/PTSD populations, highlights the benefits and potential pitfalls of secondary analytic techniques, and uses a case example of one of the largest effectiveness trials of behavioral treatment for co-occurring SUD/PTSD conducted within the National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) and producing 19 publications. The paper concludes with implications of this secondary analytic approach to improve addiction researchers' ability to identify best practices for community-based treatment of these disorders. Innovative methods are needed to maximize the benefits of clinical studies and better support SUD/PTSD treatment options for both specialty and non-specialty healthcare settings. Moving forward, planning for and description of secondary analyses in randomized trials should be given equal consideration and care to the primary outcome analysis. Copyright © 2015 Elsevier Inc. All rights reserved.

A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study.

PubMed

Wozniak, Janet; Faraone, Stephen V; Chan, James; Tarko, Laura; Hernandez, Mariely; Davis, Jacqueline; Woodworth, K Yvonne; Biederman, Joseph

2015-11-01

We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders. Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013. Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P <.05). Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size. ClinicalTrials.gov identifier: NCT01396486. © Copyright 2015 Physicians Postgraduate Press, Inc.

No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

PubMed

Schotanus, M G M; Pilot, P; Kaptein, B L; Draijer, W F; Tilman, P B J; Vos, R; Kort, N P

2017-09-01

A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. Randomized, single-blind, controlled trial, Level I.

Design of the Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial.

PubMed

Bradford, Andrew; Lees, Kennedy

2000-01-01

The Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial is a multicentre,randomised, placebo-controlled trial of magnesium sulphate (MgSO4) funded by the UK Medical Research Council. When complete, it will be the largest single neuroprotective study undertaken to date. Conscious patients presenting within 12 h of acute stroke with limb weakness are eligible. The primary outcome measure is combined death and disability as measured using the Barthel Index at 90-day follow up. By randomizing 2700 patients, the study will have 84% power to detect a 5.5% absolute reduction in the primary end-point. By April 2000, 86 centres were participating, with representation in Canada, USA, Europe, South America, Singapore and Australia. So far, 1206 patients have been randomised, of whom 37% were treated within 6 h. Overall 3-month mortality was 20% and the primary outcome event rate was 43%. The study is ongoing and centres worldwide are encouraged to participate.

Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

PubMed Central

Thase, Michael E.

2010-01-01

Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

Survival of Patients Receiving a Primary Prevention Implantable Cardioverter-Defibrillator in Clinical Practice vs Clinical Trials

PubMed Central

Al-Khatib, Sana M.; Hellkamp, Anne; Bardy, Gust H.; Hammill, Stephen; Jackson Hall, W.; Mark, Daniel B.; Anstrom, Kevin J.; Curtis, Jeptha; Al-Khalidi, Hussein; Curtis, Lesley H.; Heidenreich, Paul; Peterson, Eric D.; Sanders, Gillian; Clapp-Channing, Nancy; Lee, Kerry L.; Moss, Arthur J.

2013-01-01

Importance Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown. Objective To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n=742) and SCD-HeFT (n=829). Design, Setting, and Patients Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score–matched patients) or the SCD-HeFT criteria (3352 propensity score–matched patients). Mortality data for the registry patients were collected through December 31, 2009. Main Outcome Measures Cox proportional hazards models were used to compare mortality from any cause. Results The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II–like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85–1.31; P=.62). Likewise, the survival among SCD-HeFT–like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry vs trial hazard ratio, 1.16; 95% CI, 0.97–1.38; P=.11). Conclusions and Relevance There was no significant difference in survival between clinical trial patients randomized to receive an ICD and a similar group of clinical registry patients who received a primary prevention ICD. Our findings support the continued use of primary prevention ICDs in similar patients seen in clinical practice. Trial Registration clinicaltrials.gov Identifier: NCT00000609 PMID:23280225

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 results with two prior RCTs, also showed no significant effect of treatment with IVIG. ClinicalTrials.gov NCT00606905. PMID:20634190

Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials.

PubMed

Leonardi-Bee, Jo; Bath, Philip M W; Bousser, Marie-Germaine; Davalos, Antoni; Diener, Hans-Christoph; Guiraud-Chaumeil, Bernard; Sivenius, Juhani; Yatsu, Frank; Dewey, Michael E

2005-01-01

Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials. Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.

Twenty-year perspective of randomized controlled trials for surgery of chronic nonspecific low back pain: citation bias and tangential knowledge.

PubMed

Andrade, Nicholas S; Flynn, John P; Bartanusz, Viktor

2013-11-01

After decades of clinical research, the role of surgery for chronic nonspecific low back pain (CNLBP) remains equivocal. Despite significant intellectual, human, and economic investments into randomized controlled trials (RCTs) in the past two decades, the role of surgery in the treatment for CNLBP has not been clarified. To delineate the historical research agenda of surgical RCTs for CNLBP performed between 1993 and 2012 investigating whether conclusions from earlier published trials influenced the choice of research questions of subsequent RCTs on elucidating the role of surgery in the management of CNLBP. Literature review. We searched the literature for all RCTs involving surgery for CNLBP. We reviewed relevant studies to identify the study question, comparator arms, and sample size. Randomized controlled trials were classified as "indication" trials if they evaluated the effectiveness of surgical therapy versus nonoperative care or as "technical" if they compared different surgical techniques, adjuncts, or procedures. We used citation analysis to determine the impact of trials on subsequent research in the field. Altogether 33 technical RCTs (3,790 patients) and 6 indication RCTs (981 patients) have been performed. Since 2007, despite the unclear benefits of surgery reported by the first four indication trials published in 2001 to 2006, technical trials have continued to predominate (16 vs. 2). Of the technical trials, types of instrumentation (13 trials, 1,332 patients), bone graft materials and substitutes (11 trials, 833 patients), and disc arthroplasty versus fusion (5 trials, 1,337 patients) were the most common comparisons made. Surgeon authors have predominantly cited one of the indication trials that reported more favorable results for surgery, despite a lack of superior methodology or sample size. Trials evaluating bone morphogenic protein, instrumentation, and disc arthroplasty were all cited more frequently than the largest trial of surgical versus nonsurgical therapy. The research agenda of RCTs for surgery of CNLBP has not changed substantially in the last 20 years. Technical trials evaluating nuances of surgical techniques significantly predominate. Despite the publication of four RCTs reporting equivocal benefits of surgery for CNLBP between 2001 and 2006, there was no change in the research agenda of subsequent RCTs, and technical trials continued to outnumber indication trials. Rather than clarifying what, if any, indications for surgery exist, investigators in the field continue to analyze variations in surgical technique, which will probably have relatively little impact on patient outcomes. As a result, clinicians unfortunately have little evidence to advise patients regarding surgical intervention for CNLBP. Copyright © 2013 Elsevier Inc. All rights reserved.

Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols.

PubMed

Mhaskar, Rahul; Djulbegovic, Benjamin; Magazin, Anja; Soares, Heloisa P; Kumar, Ambuj

2012-06-01

To assess whether the reported methodological quality of randomized controlled trials (RCTs) reflects the actual methodological quality and to evaluate the association of effect size (ES) and sample size with methodological quality. Systematic review. This is a retrospective analysis of all consecutive phase III RCTs published by eight National Cancer Institute Cooperative Groups up to 2006. Data were extracted from protocols (actual quality) and publications (reported quality) for each study. Four hundred twenty-nine RCTs met the inclusion criteria. Overall reporting of methodological quality was poor and did not reflect the actual high methodological quality of RCTs. The results showed no association between sample size and actual methodological quality of a trial. Poor reporting of allocation concealment and blinding exaggerated the ES by 6% (ratio of hazard ratio [RHR]: 0.94; 95% confidence interval [CI]: 0.88, 0.99) and 24% (RHR: 1.24; 95% CI: 1.05, 1.43), respectively. However, actual quality assessment showed no association between ES and methodological quality. The largest study to date shows that poor quality of reporting does not reflect the actual high methodological quality. Assessment of the impact of quality on the ES based on reported quality can produce misleading results. Copyright © 2012 Elsevier Inc. All rights reserved.

Do Personality Problems Improve During Psychodynamic Supportive-Expressive Psychotherapy? Secondary Outcome Results From a Randomized Controlled Trial for Psychiatric Outpatients with Personality Disorders

PubMed Central

Vinnars, Bo; Thormählen, Barbro; Gallop, Robert; Norén, Kristina; Barber, Jacques P.

2009-01-01

Studies involving patients with personality disorders (PD) have not focused on improvement of core aspects of the PD. This paper examines changes in quality of object relations, interpersonal problems, psychological mindedness, and personality traits in a sample of 156 patients with DSM-IV PD diagnoses being randomized to either manualized or non manualized dynamic psychotherapy. Effect sizes adjusted for symptomatic change and reliable change indices were calculated. We found that both treatments were equally effective at reducing personality pathology. Only in neuroticism did the non manualized group do better during the follow-up period. The largest improvement was found in quality of object relations. For the remaining variables only small and clinically insignificant magnitudes of change were found. PMID:20161588

Serological Markers of Sand Fly Exposure to Evaluate Insecticidal Nets against Visceral Leishmaniasis in India and Nepal: A Cluster-Randomized Trial

PubMed Central

Gidwani, Kamlesh; Picado, Albert; Rijal, Suman; Singh, Shri Prakash; Roy, Lalita; Volfova, Vera; Andersen, Elisabeth Wreford; Uranw, Surendra; Ostyn, Bart; Sudarshan, Medhavi; Chakravarty, Jaya; Volf, Petr; Sundar, Shyam; Boelaert, Marleen; Rogers, Matthew Edward

2011-01-01

Background Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial. Methods As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention. Results A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83–0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80–1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi. Conclusions This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions. PMID:21931871

Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomized trial.

PubMed

Gidwani, Kamlesh; Picado, Albert; Rijal, Suman; Singh, Shri Prakash; Roy, Lalita; Volfova, Vera; Andersen, Elisabeth Wreford; Uranw, Surendra; Ostyn, Bart; Sudarshan, Medhavi; Chakravarty, Jaya; Volf, Petr; Sundar, Shyam; Boelaert, Marleen; Rogers, Matthew Edward

2011-09-01

Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial. As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention. A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83-0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80-1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi. This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions.

Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery.

PubMed

Lamy, Andre; Devereaux, Philip J; Prabhakaran, Dorairaj; Hu, Shengshou; Piegas, Leopoldo S; Straka, Zbynek; Paolasso, Ernesto; Taggart, David; Lanas, Fernando; Akar, A Ruchan; Jain, Anil; Noiseux, Nicolas; Ou, Yongning; Chrolavicius, Susan; Ng, Jennifer; Yusuf, Salim

2012-01-01

Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart (off pump) for coronary artery bypass grafting (CABG) surgery versus on-pump CABG. Prior trials had few events and relatively short follow-up. There is a need for a large randomized, controlled trial with long-term follow-up to inform both the short- and long-term impact of the 2 approaches to CABG. We plan to randomize 4,700 patients in whom CABG is planned to undergo the procedure on pump or off pump. The coprimary outcomes are a composite of total mortality, myocardial infarction (MI), stroke, and renal failure at 30 days and a composite of total mortality, MI, stroke, renal failure, and repeat revascularization at 5 years. We will also undertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery. Other outcomes include neurocognitive dysfunction, recurrence of angina, cardiovascular mortality, blood transfusions, and quality of life. As of May 3, 2011, CORONARY has recruited >3,884 patients from 79 centers in 19 countries. Currently, patient's mean age is 67.6 years, 80.7% are men, 47.0% have a history of diabetes, 51.4% have a history of smoking, and 34.4% had a previous MI. In addition, 20.9% of patients have a left main disease, and 96.6% have double or triple vessel disease. CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG. Its results will lead to a better understanding of the safety and efficacy of off-pump CABG. Copyright © 2012 Mosby, Inc. All rights reserved.

Does a balanced transfusion ratio of plasma to packed red blood cells improve outcomes in both trauma and surgical patients? A meta-analysis of randomized controlled trials and observational studies.

PubMed

Rahouma, Mohamed; Kamel, Mohamed; Jodeh, Diana; Kelley, Thomas; Ohmes, Lucas B; de Biasi, Andreas R; Abouarab, Ahmed A; Benedetto, Umberto; Guy, T Sloane; Lau, Christopher; Lee, Paul C; Girardi, Leonard N; Gaudino, Mario

2017-09-23

The effect of high transfusion ratios of fresh frozen plasma (FFP): packed red blood cell (RBC) on mortality is still controversial. Observational evidence contradicts a recent randomized controlled trial regarding mortality benefit. This is an updated meta-analysis, including a non-trauma cohort. Patients were grouped into high vs. low based on FFP:RBC ratio. Primary outcomes were 24-h and 30-day/in-hospital mortality. Secondary outcomes were acute respiratory distress syndrome and acute lung injury rates. Random model and leave-one-out-analyses were used. In 36 studies, lower ratio showed poorer 24-h and 30-day survival (p < 0.001). In trauma and non-trauma settings, a lower ratio was associated with worse 24-h and 30-day mortality (P < 0.001). A ratio of 1:1.5 provided the largest 24-h and 30-day survival benefit (p < 0.001). The ratio was not associated with ARDS or ALI. High FFP:RBC ratio confers survival benefits in trauma and non-trauma settings, with the highest survival benefit at 1:1.5. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of print advertising for a bipolar disorder study.

PubMed

Roy, Sumeet; Patel, Shilpa; Sheehan, Kathy Harnett; Janavs, Juris; Sheehan, David

2008-01-01

Using quality and quantity of responses, this study evaluated the efficacy of advertising in print media for a bipolar disorder clinical trial. We analyzed the corresponding quantity of calls generated and the cost per patient yield at each of the standard study milestones, spending on print advertising. Quality of calls was based on the attrition rates at each of the study stages. Five hundred and twenty-six calls were received over a 28-month period (February 2004 to June 2006). The largest number of calls were received early in the week (Monday, 25.6%; Tuesday, 23.5%; Wednesday, 18.8%), corresponding with increased advertisements toward the end of the previous week. From the total calls received, 17.14% were eligible for a screening visit, 10.28% were randomized, 9.14% were evaluable, and 7% completed the 8-week study. Sixty percent of the subjects who attended the screening visit were randomized and 68.5% of the randomized subjects completed the study. The yield from phone calls responding to print advertising for a bipolar disorder study was 7%, costing $1,330 per evaluable subject and $1,725 per completed subject. These figures may be useful benchmarks in recruitment planning and budgeting for participants in clinical trials on bipolar disorder.

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kilpeläinen, Tuomas P; Mäkinen, Tuukka; Karhunen, Pekka J; Aro, Jussi; Lahtela, Jorma; Taari, Kimmo; Talala, Kirsi; Tammela, Teuvo L J; Auvinen, Anssi

2016-12-01

Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial. Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N=442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms. Overdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14-1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82-1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ=0.88) in the SA and 95.4% (κ=0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80-1.06). A small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Randomized Controlled Trial of Mindfulness Meditation for Chronic Insomnia

PubMed Central

Ong, Jason C.; Manber, Rachel; Segal, Zindel; Xia, Yinglin; Shapiro, Shauna; Wyatt, James K.

2014-01-01

Study Objectives: To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. Design: Three-arm, single-site, randomized controlled trial. Setting: Academic medical center. Participants: Fifty-four adults with chronic insomnia. Interventions: Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. Measurements and Results: Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. Conclusions: Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. Trial Registration: Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781 Citation: Ong JC, Manber R, Segal Z, Xia Y, Shapiro S, Wyatt JK. A randomized controlled trial of mindfulness meditation for chronic insomnia. SLEEP 2014;37(9):1553-1563. PMID:25142566

Three Months of Progressive High-Load Versus Traditional Low-Load Strength Training Among Patients With Rotator Cuff Tendinopathy: Primary Results From the Double-Blind Randomized Controlled RoCTEx Trial

PubMed Central

Ingwersen, Kim Gordon; Jensen, Steen Lund; Sørensen, Lilli; Jørgensen, Hans Ri; Christensen, Robin; Søgaard, Karen; Juul-Kristensen, Birgit

2017-01-01

Background: Progressive high-load exercise (PHLE) has led to positive clinical results in patients with patellar and Achilles tendinopathy. However, its effects on rotator cuff tendinopathy still need to be investigated. Purpose: To assess the clinical effects of PHLE versus low-load exercise (LLE) among patients with rotator cuff tendinopathy. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients with rotator cuff tendinopathy were recruited and randomized to 12 weeks of PHLE or LLE, stratified for concomitant administration of corticosteroid injection. The primary outcome measure was change from baseline to 12 weeks in the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, assessed in the intention-to-treat population. Results: A total of 100 patients were randomized to PHLE (n = 49) or LLE (n = 51). Mean changes in the DASH questionnaire were 7.11 points (95% CI, 3.07-11.16) and 8.39 points (95% CI, 4.35-12.44) in the PHLE and LLE groups, respectively; this corresponded to a statistically nonsignificant adjusted mean group difference of −1.37 points (95% CI, −6.72 to 3.99; P = .61). Similar nonsignificant results were seen for pain, range of motion, and strength. However, a significant interaction effect was found between the 2 groups and concomitant corticosteroid use (P = .028), with the largest positive change in DASH in favor of PHLE for the group receiving concomitant corticosteroid. Conclusion: The study results showed no superior benefit from PHLE over traditional LLE among patients with rotator cuff tendinopathy. Further investigation of the possible interaction between exercise type and corticosteroid injection is needed to establish optimal and potentially synergistic combinations of these 2 factors. Registration: NCT01984203 (ClinicalTrials.gov identifier): Rotator Cuff Tendinopathy Exercise Trial (RoCTEx). PMID:28875153

A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism.

PubMed

Hardan, Antonio Y; Gengoux, Grace W; Berquist, Kari L; Libove, Robin A; Ardel, Christina M; Phillips, Jennifer; Frazier, Thomas W; Minjarez, Mendy B

2015-08-01

With rates of autism diagnosis continuing to rise, there is an urgent need for effective and efficient service delivery models. Pivotal Response Treatment (PRT) is considered an established treatment for autism spectrum disorder (ASD); however, there have been few well-controlled studies with adequate sample size. The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group (PRTG) for targeting language deficits in young children with ASD. Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG (N = 27) or psychoeducation group (PEG; N = 26) for 12 weeks. The PRTG taught parents behavioral techniques to facilitate language development. The PEG taught general information about ASD (clinical trial NCT01881750; http://www.clinicaltrials.gov). Analysis of child utterances during the structured laboratory observation (primary outcome) indicated that, compared with children in the PEG, children in the PRTG demonstrated greater improvement in frequency of utterances (F(2, 43) = 3.53, p = .038, d = 0.42). Results indicated that parents were able to learn PRT in a group format, as the majority of parents in the PRTG (84%) met fidelity of implementation criteria after 12 weeks. Children also demonstrated greater improvement in adaptive communication skills (Vineland-II) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG. This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date. The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children, especially in functional and adaptive communication skills. Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms. © 2014 Association for Child and Adolescent Mental Health.

Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1.

PubMed

Elm, Jordan J

2012-10-01

Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care. Copyright © 2012 Movement Disorder Society.

Critical Analysis of the Efficacy of Meditation Therapies for Acute and Subacute Phase Treatment of Depressive Disorders: A Systematic Review

PubMed Central

Jain, Felipe A.; Walsh, Roger N.; Eisendrath, Stuart J.; Christensen, Scott; Cahn, B. Rael

2014-01-01

Background Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, due to a lower side-effect burden, potential reduction of polypharmacy, as well as theoretical considerations that such interventions may target some of the cognitive roots of depression. We aimed to determine the state of the evidence supporting this application. Methods Randomized, controlled trials of techniques meeting the Agency for Healthcare Research and Quality (AHRQ) definition of meditation, for participants suffering from clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e. how they were applied) components, and trial outcomes were reviewed. Results Eighteen studies meeting inclusionary criteria were identified, encompassing seven distinct techniques and 1173 patients, with Mindfulness-Based Cognitive Therapy comprising the largest proportion. Studies including patients suffering from acute major depressive episodes (N = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (N = 8), demonstrated moderate to large reductions in depression symptoms within group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. Conclusions A substantial body of evidence indicates that meditation therapies may have salutary effects on patients suffering from clinical depressive disorders during the acute and subacute phases of treatment. Due to methodological deficiences and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium. PMID:25591492

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

Status update and interim results from the asymptomatic carotid surgery trial-2 (ACST-2).

PubMed

Halliday, Alison; Bulbulia, Richard; Gray, William; Naughten, Ally; den Hartog, Anne; Delmestri, Antonella; Wallis, Carol; le Conte, Stephanie; Macdonald, Sumaira

2013-11-01

ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. ISRCTN21144362. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)

PubMed Central

2012-01-01

Background One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. Methods In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI) was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day), Pycnogenol (150 mg/day), or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation, oxidative stress and safety) as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms). The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration. ARCLI will represent one of the largest and most comprehensive experimental clinical trials in which supplements are administered to elderly participants. Results from ARCLI may help develop novel preventative health practices and nutritional/pharmacological targets in the elderly for cognitive and brain health. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487910 PMID:22390677

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

PubMed

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

2013-01-01

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

Efficacy of Multivitamin/mineral Supplementation to Reduce Chronic Disease Risk: A Critical Review of the Evidence from Observational Studies and Randomized Controlled Trials.

PubMed

Angelo, Giana; Drake, Victoria J; Frei, Balz

2015-01-01

We reviewed recent scientific evidence regarding the effects of multivitamin/mineral (MVM) supplements on risk of chronic diseases, including cancer, cardiovascular disease, and age-related eye diseases. Data from randomized controlled trials (RCTs) and observational, prospective cohort studies were examined. The majority of scientific studies investigating the use of MVM supplements in chronic disease risk reduction reported no significant effect. However, the largest and longest RCT of MVM supplements conducted to date, the Physicians' Health Study II (PHS II), found a modest and significant reduction in total and epithelial cancer incidence in male physicians, consistent with the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) trial. In addition, PHS II found a modest and significant reduction in the incidence of nuclear cataract, in agreement with several other RCTs and observational, prospective cohort studies. The effects of MVM use on other subtypes of cataract and age-related macular degeneration remain unclear. Neither RCTs nor prospective cohort studies are without their limitations. The placebo-controlled trial design of RCTs may be inadequate for nutrient interventions, and residual confounding, measurement error, and the possibility of reverse causality are inherent to any observational study. National surveys show that micronutrient inadequacies are widespread in the US and that dietary supplements, of which MVMs are the most common type, help fulfill micronutrient requirements in adults and children.

Safety Planning for Military (SAFE MIL): rationale, design, and safety considerations of a randomized controlled trial to reduce suicide risk among psychiatric inpatients.

PubMed

Ghahramanlou-Holloway, Marjan; Brown, Gregory K; Currier, Glenn W; Brenner, Lisa; Knox, Kerry L; Grammer, Geoffrey; Carreno-Ponce, Jaime T; Stanley, Barbara

2014-09-01

Mental health related hospitalizations and suicide are both significant public health problems within the United States Department of Defense (DoD). To date, few evidence-based suicide prevention programs have been developed for delivery to military personnel and family members admitted for psychiatric inpatient care due to suicidal self-directed violence. This paper describes the rationale and detailed methodology for a study called Safety Planning for Military (SAFE MIL) which involves a randomized controlled trial (RCT) at the largest military treatment facility in the United States. The purpose of this study is to test the efficacy of a brief, readily accessible, and personalized treatment called the Safety Planning Intervention (Stanley and Brown, 2012). Primary outcomes, measured by blinded assessors at one and six months following psychiatric discharge, include suicide ideation, suicide-related coping, and attitudes toward help seeking. Additionally, given the study's focus on a highly vulnerable patient population, a description of safety considerations for human subjects' participation is provided. Based on this research team's experience, the implementation of an infrastructure in support of RCT research within DoD settings and the processing of regulatory approvals for a clinical trial with high risk suicidal patients are expected to take up to 18-24 months. Recommendations for expediting the advancement of clinical trials research within the DoD are provided in order to maximize cost efficacy and minimize the research to practice gap. Published by Elsevier Inc.

Design innovations and baseline findings in a long-term Parkinson’s trial: NET-PD LS-1

PubMed Central

2012-01-01

Background Based on the pre-clinical and the results of a phase 2 futility study, creatine was selected for an efficacy trial in Parkinson’s disease (PD). We present the design rationale and a description of the study cohort at baseline. Methods A randomized, multicenter, double-blind, parallel group, placebo controlled Phase 3 study of creatine (10 gm daily) in participants with early, treated PD, the Long-term Study – 1 (LS-1) is being conducted by the NINDS Exploratory Trials in Parkinson’s Disease (NET-PD) network. The study utilizes a global statistical test (GST) encompassing multiple clinical rating scales to provide a multidimensional assessment of disease progression. Results A total of 1,741 PD participants from 45 sites in the U.S. and Canada were randomized 1:1 to either 10-gm creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. Conclusions LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. PMID:23079770

Systematic review: an evaluation of major commercial weight loss programs in the United States.

PubMed

Tsai, Adam Gilden; Wadden, Thomas A

2005-01-04

Each year millions of Americans enroll in commercial and self-help weight loss programs. Health care providers and their obese patients know little about these programs because of the absence of systematic reviews. To describe the components, costs, and efficacy of the major commercial and organized self-help weight loss programs in the United States that provide structured in-person or online counseling. Review of company Web sites, telephone discussion with company representatives, and search of the MEDLINE database. Randomized trials at least 12 weeks in duration that enrolled only adults and assessed interventions as they are usually provided to the public, or case series that met these criteria, stated the number of enrollees, and included a follow-up evaluation that lasted 1 year or longer. Data were extracted on study design, attrition, weight loss, duration of follow-up, and maintenance of weight loss. We found studies of eDiets.com, Health Management Resources, Take Off Pounds Sensibly, OPTIFAST, and Weight Watchers. Of 3 randomized, controlled trials of Weight Watchers, the largest reported a loss of 3.2% of initial weight at 2 years. One randomized trial and several case series of medically supervised very-low-calorie diet programs found that patients who completed treatment lost approximately 15% to 25% of initial weight. These programs were associated with high costs, high attrition rates, and a high probability of regaining 50% or more of lost weight in 1 to 2 years. Commercial interventions available over the Internet and organized self-help programs produced minimal weight loss. Because many studies did not control for high attrition rates, the reported results are probably a best-case scenario. With the exception of 1 trial of Weight Watchers, the evidence to support the use of the major commercial and self-help weight loss programs is suboptimal. Controlled trials are needed to assess the efficacy and cost-effectiveness of these interventions.

Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial.

PubMed

Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

2016-06-01

The Systolic Blood Pressure Intervention Trial is a multicenter, randomized clinical trial of 9361 participants with hypertension who are ≥50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal <120 mm Hg) compared to standard control (systolic blood pressure goal <140 mm Hg) on cardiovascular events using commonly prescribed antihypertensive medications and lifestyle modification. To describe the recruitment strategies and lessons learned during recruitment of the Systolic Blood Pressure Intervention Trial cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥75 years, women, and minorities. In collaboration with the National Institutes of Health Project Office and Systolic Blood Pressure Intervention Trial Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began on 8 November 2010 and ended on 15 March 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Recruitment was scheduled to last 24 months to enroll a target of 9250 participants; in just over 28 months, the trial enrolled 9361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by Systolic Blood Pressure Intervention Trial staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, Internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized/number screened) was 64% (9361 randomized/14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those aged ≥75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional clinics were included and inclusion criteria were broadened, keeping event rates and trial power in mind. As overall recruitment improved, a greater focus on subgroup recruitment was implemented. Systolic Blood Pressure Intervention Trial met its overall projected recruitment goal using diverse, locally adapted enrollment strategies to specifically target persons with cardiovascular disease, chronic kidney disease, ≥75 years old, women, and minority subgroups. The trial exceeded its recruitment goal for minorities but found it a challenge to meet the competing demands of the targeted goals for recruiting into the remaining four subgroups. Important lessons include the imperative to monitor the recruitment process carefully, decide early to add new clinics or modify inclusion and exclusion criteria if recruitment lags, and consider limiting enrollment to subgroups only. We found benefit in using multiple recruitment sources simultaneously; mass mailing produced the largest number of participants, but referrals resulted in the greater randomization yield. © The Author(s) 2016.

Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health.

PubMed

McEvoy, Cindy T; Milner, Kristin F; Scherman, Ashley J; Schilling, Diane G; Tiller, Christina J; Vuylsteke, Brittany; Shorey-Kendrick, Lyndsey E; Spindel, Eliot R; Schuff, Robert; Mitchell, Julie; Peters, Dawn; Metz, Jill; Haas, David; Jackson, Keith; Tepper, Robert S; Morris, Cynthia D

2017-07-01

Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3months of age in infants delivered to pregnant smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12months and pulmonary function testing at 12months of age. Women are randomized between 13 and 23weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12months of age and incidence of wheezing and respiratory illness through 12months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Task shifting of frontline community health workers for cardiovascular risk reduction: design and rationale of a cluster randomised controlled trial (DISHA study) in India.

PubMed

Jeemon, Panniyammakal; Narayanan, Gitanjali; Kondal, Dimple; Kahol, Kashvi; Bharadwaj, Ashok; Purty, Anil; Negi, Prakash; Ladhani, Sulaiman; Sanghvi, Jyoti; Singh, Kuldeep; Kapoor, Deksha; Sobti, Nidhi; Lall, Dorothy; Manimunda, Sathyaprakash; Dwivedi, Supriya; Toteja, Gurudyal; Prabhakaran, Dorairaj

2016-03-15

Effective task-shifting interventions targeted at reducing the global cardiovascular disease (CVD) epidemic in low and middle-income countries (LMICs) are urgently needed. DISHA is a cluster randomised controlled trial conducted across 10 sites (5 in phase 1 and 5 in phase 2) in India in 120 clusters. At each site, 12 clusters were randomly selected from a district. A cluster is defined as a small village with 250-300 households and well defined geographical boundaries. They were then randomly allocated to intervention and control clusters in a 1:1 allocation sequence. If any of the intervention and control clusters were <10 km apart, one was dropped and replaced with another randomly selected cluster from the same district. The study included a representative baseline cross-sectional survey, development of a structured intervention model, delivery of intervention for a minimum period of 18 months by trained frontline health workers (mainly Anganwadi workers and ASHA workers) and a post intervention survey in a representative sample. The study staff had no information on intervention allocation until the completion of the baseline survey. In order to ensure comparability of data across sites, the DISHA study follows a common protocol and manual of operation with standardized measurement techniques. Our study is the largest community based cluster randomised trial in low and middle-income country settings designed to test the effectiveness of 'task shifting' interventions involving frontline health workers for cardiovascular risk reduction. CTRI/2013/10/004049 . Registered 7 October 2013.

Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial.

PubMed

Sluyter, John D; Camargo, Carlos A; Waayer, Debbie; Lawes, Carlene M M; Toop, Les; Khaw, Kay-Tee; Scragg, Robert

2017-12-13

Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50-84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; range = 0.9-1.5 years), either (1) vitamin D₃ 200,000 IU, followed by monthly 100,000 IU doses ( n = 226); or (2) placebo monthly ( n = 216). At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome). Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group. There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants. However, among ever-smokers ( n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL ( p = 0.03). FEV1 increases were larger among vitamin D-deficient ever-smokers ( n = 54): 122 (8, 236) mL ( p = 0.04). FEV1 improvements were largest among ever-smokers with asthma/COPD ( n = 60): 160 (53, 268) mL ( p = 0.004). Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD.

Sunscreen use and intentional exposure to ultraviolet A and B radiation: a double blind randomized trial using personal dosimeters

PubMed Central

Autier, P; Doré, J-F; Reis, A C; Grivegnée, A; Ollivaud, L; Truchetet, F; Chamoun, E; Rotmensz, N; Severi, G; Césarini, J-P

2000-01-01

A previous randomized trial found that sunscreen use could extend intentional sun exposure, thereby possibly increasing the risk of cutaneous melanoma. In a similarly designed trial, we examined the effect of the use of sunscreens having different sun protection factor (SPF) on actual exposure to ultraviolet B (UVB) and ultraviolet A (UVA) radiation. In June 1998, 58 European participants 18–24 years old were randomized to receive a SPF 10 or 30 sunscreens and were asked to complete daily records of their sun exposure during their summer holidays of whom 44 utilized a personal UVA and UVB dosimeter in a standard way during their sunbathing sessions. The median daily sunbathing duration was 2.4 hours in the SPF 10 group and 3.0 hours in the SPF 30 group (P = 0.054). The increase in daily sunbathing duration was paralleled by an increase in daily UVB exposure, but not by changes in UVA or UVB accumulated over all sunbathing sessions, or in daily UVA exposure. Of all participants, those who used the SPF 30 sunscreen and had no sunburn spent the highest number of hours in sunbathing activities. Differences between the two SPF groups in total number of sunbathing hours, daily sunbathing duration, and daily UVB exposure were largest among participants without sunburn during holidays. Among those with sunburn, the differences between the two groups tended to reduce. In conclusion, sunscreens used during sunbathing tended to increase the duration of exposures to doses of ultraviolet radiation below the sunburn threshold. © 2000 Cancer Research Campaign PMID:11027441

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

Excitation-based and informational masking of a tonal signal in a four-tone masker.

PubMed

Leibold, Lori J; Hitchens, Jack J; Buss, Emily; Neff, Donna L

2010-04-01

This study examined contributions of peripheral excitation and informational masking to the variability in masking effectiveness observed across samples of multi-tonal maskers. Detection thresholds were measured for a 1000-Hz signal presented simultaneously with each of 25, four-tone masker samples. Using a two-interval, forced-choice adaptive task, thresholds were measured with each sample fixed throughout trial blocks for ten listeners. Average thresholds differed by as much as 26 dB across samples. An excitation-based model of partial loudness [Moore, B. C. J. et al. (1997). J. Audio Eng. Soc. 45, 224-237] was used to predict thresholds. These predictions accounted for a significant portion of variance in the data of several listeners, but no relation between the model and data was observed for many listeners. Moreover, substantial individual differences, on the order of 41 dB, were observed for some maskers. The largest individual differences were found for maskers predicted to produce minimal excitation-based masking. In subsequent conditions, one of five maskers was randomly presented in each interval. The difference in performance for samples with low versus high predicted thresholds was reduced in random compared to fixed conditions. These findings are consistent with a trading relation whereby informational masking is largest for conditions in which excitation-based masking is smallest.

Mediterranean diet and life expectancy; beyond olive oil, fruits and vegetables

PubMed Central

Martinez-Gonzalez, Miguel A.; Martín-Calvo, Nerea

2018-01-01

Purpose to review the recent relevant evidence of the effects of the Mediterranean diet and lifestyle on health (2015 and first months of 2016). Recent findings Large observational prospective epidemiological studies with adequate control of confounding and two large randomized trials support the benefits of the Mediterranean dietary pattern to increase life expectancy, reduce the risk of major chronic disease, and improve quality of life and well-being. Recently, 19 new reports from large prospective studies showed –with nearly perfect consistency– strong benefits of the Mediterranean diet to reduce the risk of myocardial infarction, stroke, total mortality, heart failure and disability. Interestingly, two large and well-conducted cohorts reported significant cardiovascular benefits after using repeated measurements of diet during a long follow-up period. Besides, PREDIMED, the largest randomized trial with Mediterranean diet, recently reported benefits of this dietary pattern to prevent cognitive decline and breast cancer. Summary In the era of evidence-based medicine, the Mediterranean diet represents the gold standard in preventive medicine, probably due to the harmonic combination of many elements with antioxidant and antiinflammatory properties, which overwhelm any single nutrient or food item. The whole seems more important than the sum of its parts. PMID:27552476

Mediterranean diet and life expectancy; beyond olive oil, fruits, and vegetables.

PubMed

Martinez-Gonzalez, Miguel A; Martin-Calvo, Nerea

2016-11-01

The recent relevant evidence of the effects of the Mediterranean diet (MedDiet) and lifestyle on health (2015 and first months of 2016). Large observational prospective epidemiological studies with adequate control of confounding and two large randomized trials support the benefits of the Mediterranean dietary pattern to increase life expectancy, reduce the risk of major chronic disease, and improve quality of life and well-being. Recently, 19 new studies from large prospective studies showed - with nearly perfect consistency - strong benefits of the MedDiet to reduce the risk of myocardial infarction, stroke, total mortality, heart failure, and disability. Interestingly, two large and well conducted cohorts reported significant cardiovascular benefits after using repeated measurements of diet during a long follow-up period. In addition, Prevención con Dieta Mediterránea, the largest randomized trial with MedDiet, recently reported benefits of this dietary pattern to prevent cognitive decline and breast cancer. In the era of evidence-based medicine, the MedDiet represents the gold standard in preventive medicine, probably because of the harmonic combination of many elements with antioxidant and anti-inflammatory properties, which overwhelm any single nutrient or food item. The whole seems more important than the sum of its parts.

Acceptability and preliminary efficacy of a tailored online HIV/STI testing intervention for young men who have sex with men: the Get Connected! program.

PubMed

Bauermeister, José A; Pingel, Emily S; Jadwin-Cakmak, Laura; Harper, Gary W; Horvath, Keith; Weiss, Gretchen; Dittus, Patricia

2015-10-01

Southeast Michigan accounts for over 70 % of all HIV/STI cases in the state, with young men who have sex with men (YMSM) between the ages of 13 and 24 encumbering the largest burden in HIV/STI incidence. Using community-based participatory research principles, we developed and pilot tested a web-based, randomized control trial seeking to promote HIV/STI testing ("Get Connected!") among YMSM (N = 130; ages 15-24). Randomized participants completed a baseline assessment and shown a test-locator condition (control) or a tailored, personalized site (treatment). At 30-day follow-up, we found high acceptability among YMSM in both conditions, yet higher credibility of intervention content among YMSM in the treatment group (d = .55). Furthermore, 30 participants reported testing by following, with the majority of these participants (73.3 %; n = 22) completing the treatment condition, a clinically meaningful effect (d = .34) suggesting preliminary efficacy for the intervention. These results demonstrate the potential of the intervention, and suggest that a larger efficacy trial may be warranted.

Polycystic Ovary Syndrome: Effect and Mechanisms of Acupuncture for Ovulation Induction

PubMed Central

Johansson, Julia; Stener-Victorin, Elisabet

2013-01-01

Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by the coexistence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (PCO). PCOS also represents the largest part of female oligoovulatory infertility, and the management of ovulatory and menstrual dysfunction, comprises a third of the high costs of PCOS treatment. Current pharmacological and surgical treatments for reproductive symptoms are effective, however, associated with negative side effects, such as cardiovascular complications and multiple pregnancies. For menstrual irregularities and ovulation induction in women with PCOS, acupuncture has indicated beneficial effects. This review will focus on the results from randomized controlled acupuncture trials for regulation of menstrual dysfunction and for inducing ovulation in women with PCOS although there are uncontrolled trials with nonetheless interesting results. Animal experimental studies will be further discussed when they can provide a more mechanistic explanatory view. PMID:24073009

The RIVUR Trial: Profile and Baseline Clinical Associations of Children With Vesicoureteral Reflux

PubMed Central

Hoberman, Alejandro; Mattoo, Tej K.; Mathews, Ranjiv; Keren, Ron; Chesney, Russell W.; Moxey-Mims, Marva; Greenfield, Saul P.

2013-01-01

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is diagnosed in ∼30% to 40% of children who have imaging studies after urinary tract infections (UTIs). Our goal is to characterize children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial and to compare our study cohort with those from previously published studies. METHODS: RIVUR investigators from 19 pediatric sites in the United States recruited 607 children with grade I through IV VUR. Children were enrolled after a first or second UTI. This cross-sectional report of baseline data includes extensive clinical, parental report, and imaging study results. RESULTS: RIVUR recruited 607 children (558 girls, 49 boys) with grade I (11%), II (42%), III (38%), or IV (8%) reflux. The median age was 12 months, and most children (91%) were enrolled after their first UTI. The UTI leading to enrollment was both febrile and symptomatic for 323 children, febrile only in 197 children, and symptomatic only in 86. Renal involvement at baseline as documented by a 99mTc dimercaptosuccinic acid scan was uncommon with cortical defects identified in 89 (15%) children. Bladder and bowel dysfunction was identified in 71 (56%) of 126 toilet-trained subjects assessed. CONCLUSIONS: RIVUR is the largest prospective, randomized trial for children with primary VUR to date, comparing prophylaxis with placebo. The study sample comprises patients from 19 pediatric clinical sites in the United States, whose demographic and clinical characteristics may differ from those of children enrolled in previous trials from other countries. PMID:23753091

Animal-Assisted Therapies for Youth with or at risk for Mental Health Problems: A Systematic Review.

PubMed

Hoagwood, Kimberly Eaton; Acri, Mary; Morrissey, Meghan; Peth-Pierce, Robin

2017-01-01

To systematically review experimental evidence about animal-assisted therapies (AAT) for children or adolescents with or at risk for mental health conditions, we reviewed all experimental AAT studies published between 2000-2015, and compared studies by animal type, intervention, and outcomes. Studies were included if used therapeutically for children and adolescents (≤21 years) with or at risk for a mental health problem; used random assignment or a waitlist comparison/control group; and included child-specific outcome data. Of 1,535 studies, 24 met inclusion criteria. Of 24 studies identified, almost half were randomized controlled trials, with 9 of 11 published in the past two years. The largest group addresses equine therapies for autism. Findings are generally promising for positive effects associated with equine therapies for autism and canine therapies for childhood trauma. The AAT research base is slim; a more focused research agenda is outlined.

A remote monitoring and telephone nurse coaching intervention to reduce readmissions among patients with heart failure: study protocol for the Better Effectiveness After Transition - Heart Failure (BEAT-HF) randomized controlled trial.

PubMed

Black, Jeanne T; Romano, Patrick S; Sadeghi, Banafsheh; Auerbach, Andrew D; Ganiats, Theodore G; Greenfield, Sheldon; Kaplan, Sherrie H; Ong, Michael K

2014-04-13

Heart failure is a prevalent health problem associated with costly hospital readmissions. Transitional care programs have been shown to reduce readmissions but are costly to implement. Evidence regarding the effectiveness of telemonitoring in managing the care of this chronic condition is mixed. The objective of this randomized controlled comparative effectiveness study is to evaluate the effectiveness of a care transition intervention that includes pre-discharge education about heart failure and post-discharge telephone nurse coaching combined with home telemonitoring of weight, blood pressure, heart rate, and symptoms in reducing all-cause 180-day hospital readmissions for older adults hospitalized with heart failure. A multi-center, randomized controlled trial is being conducted at six academic health systems in California. A total of 1,500 patients aged 50 years and older will be enrolled during a hospitalization for treatment of heart failure. Patients in the intervention group will receive intensive patient education using the 'teach-back' method and receive instruction in using the telemonitoring equipment. Following hospital discharge, they will receive a series of nine scheduled health coaching telephone calls over 6 months from nurses located in a centralized call center. The nurses also will call patients and patients' physicians in response to alerts generated by the telemonitoring system, based on predetermined parameters. The primary outcome is readmission for any cause within 180 days. Secondary outcomes include 30-day readmission, mortality, hospital days, emergency department (ED) visits, hospital cost, and health-related quality of life. BEAT-HF is one of the largest randomized controlled trials of telemonitoring in patients with heart failure, and the first explicitly to adapt the care transition approach and combine it with remote telemonitoring. The study population also includes patients with a wide range of demographic and socioeconomic characteristics. Once completed, the study will be a rich resource of information on how best to use remote technology in the care management of patients with chronic heart failure. ClinicalTrials.gov # NCT01360203.

Design of a Cluster-Randomized Controlled Trial of a Diabetes Prevention Program within African-American Churches: The Fit Body and Soul Study

PubMed Central

Williams, Lovoria B.; Sattin, Richard W.; Dias, James; Garvin, Jane T.; Marion, Lucy; Joshua, Thomas; Kriska, Andrea; Kramer, M. Kaye; Echouffo-Tcheugui, Justin B.; Freeman, Arin; Narayan, K.M. Venkat

2013-01-01

Evidence from varied community settings has shown that the Group Lifestyle Balance (GLB) Program and other adaptations of the Diabetes Prevention Program (DPP) intervention are effective in lowering diabetes risk. Most DPP data originated from studies of pre-diabetic whites, with only sparse evidence of the effect of DPP in African Americans (AAs) in community settings. This paper describes the design, methods, baseline characteristics and cost effective measures, of a single-blinded, cluster- randomized trial of a faith-based adaptation of the GLB program, Fit Body and Soul (FBAS). The major aims are to test efficacy and cost utility of FBAS in twenty AA churches. Randomization occurred at the church level and 604 AA overweight/obese (BMI≥25 kg/m2) adults with fasting plasma glucose range from normal to pre-diabetic received either FBAS or a health-education comparison program. FBAS is a group-based, multi-level intervention delivered by trained church health advisors (health professionals from within the church), with the goal of ≥7% weight loss, achieved through increasing physical activity, healthy eating and behavior modification. The primary outcome is weight change at 12-weeks post intervention. Secondary outcomes include hemoglobin A1C, fasting plasma glucose, waist circumference, blood pressure, physical activity level, quality of life measures, and cost-effectiveness. FBAS is the largest known cohort of AAs enrolled in a faith-based DPP translation. Reliance on health professionals from within the church for program implementation and the cost analysis are unique aspects of this trial. The design provides a model for faith-based DPPs and holds promise for program sustainability and widespread dissemination. PMID:23354313

Cost-Effectiveness analysis of Recovery Management Checkups (RMC) for adults with chronic substance use disorders: evidence from a four-year randomized trial

PubMed Central

McCollister, Kathryn E.; French, Michael T.; Freitas, Derek M.; Dennis, Michael L.; Scott, Christy K.; Funk, Rodney R.

2013-01-01

Aims This study performs the first cost-effectiveness analysis (CEA) of Recovery Management Checkups (RMC) for adults with chronic substance use disorders. Design Cost-effectiveness analysis of a randomized clinical trial of RMC. Participants were randomly assigned to a control condition of outcome monitoring (OM-only) or the experimental condition OM-plus-RMC, with quarterly follow-up for four years. Setting Participants were recruited from the largest central intake unit for substance abuse treatment in Chicago, Illinois, USA. Participants 446 participants who were 38 years old on average, 54 percent male, and predominantly African American (85%). Measurements Data on the quarterly cost per participant come from a previous study of OM and RMC intervention costs. Effectiveness is measured as the number of days of abstinence and number of substance-use-related problems. Findings Over the four-year trial, OM-plus-RMC cost on average $2,184 more than OM-only (p<0.01). Participants in OM-plus-RMC averaged 1,026 days abstinent and had 89 substance-use-related problems. OM-only averaged 932 days abstinent and reported 126 substance-use-related problems. Mean differences for both effectiveness measures were statistically significant (p<0.01). The incremental cost-effectiveness ratio for OM-plus-RMC was $23.38 per day abstinent and $59.51 per reduced substance-related problem. When additional costs to society were factored into the analysis, OM-plus-RMC was less costly and more effective than OM-only. Conclusions Recovery Management Checkups are a cost-effective and potentially cost-saving strategy for promoting abstinence and reducing substance-use-related problems among chronic substance users. PMID:23961833

Impact of a short home-based yoga programme on blood pressure in patients with hypertension: a randomized controlled trial in primary care.

PubMed

Wolff, M; Rogers, K; Erdal, B; Chalmers, J P; Sundquist, K; Midlöv, P

2016-10-01

The present study was designed to evaluate yoga's impact on blood pressure (BP) and quality of life (QOL) and on stress, depression and anxiety in patients with hypertension in a primary care setting. We conducted a multi-centre randomized controlled trial with follow-up after 12-week intervention completion. Adult primary care patients diagnosed with hypertension were randomly allocated to yoga or usual care. The intervention group performed a short home-based Kundalini yoga programme 15 min twice-daily during the 12-week intervention period. At baseline and follow-up, the participants underwent standardized BP measurements and completed questionnaires on QOL, stress, anxiety and depression. Data obtained from 191 patients (mean age 64.7 years, s.d. 8.4) allocated to yoga intervention (n=96) and control group (n=95), with a total proportion of 52% women, showed a significant reduction in systolic and diastolic BP for both groups (-3.8/-1.7 mm Hg for yoga and -4.5/-3.0 mm Hg for control groups, respectively). However, the BP reduction for the yoga group was not significantly different from control. There were small but significant improvements for the yoga group in some of the QOL and depression measures (P<0.05, Hospital Anxiety and Depression scale, HADS-D) compared with control. The findings of our study, which is the largest study from an OECD country (Organization for Economic Co-operation and Development) to date, do not support the suggestion from previous smaller studies that yoga lowers the BP. Further clinical trials are needed to confirm these findings. However, the yoga patients had other health benefits.

A low dose of three local anesthetic solutions for interscalene blockade tested by thermal quantitative sensory testing: a randomized controlled trial.

PubMed

Sermeus, Luc A; Schepens, Tom; Hans, Guy H; Morrison, Stuart G; Wouters, Kristien; Breebaart, Margaretha B; Smitz, Carine J; Vercauteren, Marcel P

2018-05-03

This randomized double-blind controlled trial compared the block characteristics of three low-dose local anesthetics at different roots in an ultrasound-guided interscalene block, using thermal quantitative sensory testing for assessing the functioning of cutaneous small nerve fibres. A total of 37 adults scheduled to undergo shoulder arthroscopy were randomized to receive 5 mL of either 0.5% levobupivacaine with and without epinephrine 1/200,000 or 0.75% ropivacaine in a single-shot interscalene block. Thermal quantitative sensory testing was performed in the C4, C5, C6 and C7 dermatomes. Detection thresholds for cold/warm sensation and cold/heat pain were measured before and at 30 min, 6, 10 and 24 h after infiltration around C5. The need for rescue medication was recorded. No significant differences between groups were found for any sensation (lowest P = 0.28). At 6 h, the largest differences in sensory thresholds were observed for the C5 dermatome. The increase in thresholds were less in C4 and C6 and minimal in C7 for all sensations. The analgesic effect lasted the longest in C5 (time × location mixed model P < 0.001 for all sensory tests). The time to rescue analgesia was significantly shorter with 0.75% ropivacaine (P = 0.02). The quantitative sensory findings showed no difference in intensity between the local anesthetics tested. A decrease in block intensity, with minimal changes in pain detection thresholds, was observed in the roots adjacent to C5, with the lowest block intensity in C7. A clinically relevant shorter duration was found with 0.75% ropivacaine compared to the other groups. Trial registration NCT 02691442.

Cost-effectiveness analysis of Recovery Management Checkups (RMC) for adults with chronic substance use disorders: evidence from a 4-year randomized trial.

PubMed

McCollister, Kathryn E; French, Michael T; Freitas, Derek M; Dennis, Michael L; Scott, Christy K; Funk, Rodney R

2013-12-01

This study performs the first cost-effectiveness analysis (CEA) of Recovery Management Checkups (RMC) for adults with chronic substance use disorders. Cost-effectiveness analysis of a randomized clinical trial of RMC. Participants were assigned randomly to a control condition of outcome monitoring (OM-only) or the experimental condition OM-plus-RMC, with quarterly follow-up for 4 years. Participants were recruited from the largest central intake unit for substance abuse treatment in Chicago, Illinois, USA. A total of 446 participants who were 38 years old on average, 54% male, and predominantly African American (85%). Data on the quarterly cost per participant come from a previous study of OM and RMC intervention costs. Effectiveness is measured as the number of days of abstinence and number of substance use-related problems. Over the 4-year trial, OM-plus-RMC cost on average $2184 more than OM-only (P < 0.01). Participants in OM-plus-RMC averaged 1026 days abstinent and had 89 substance use-related problems. OM-only averaged 932 days abstinent and reported 126 substance use-related problems. Mean differences for both effectiveness measures were statistically significant (P < 0.01). The incremental cost-effectiveness ratio for OM-plus-RMC was $23.38 per day abstinent and $59.51 per reduced substance-related problem. When additional costs to society were factored into the analysis, OM-plus-RMC was less costly and more effective than OM-only. Recovery Management Checkups are a cost-effective and potentially cost-saving strategy for promoting abstinence and reducing substance use-related problems among chronic substance users. © 2013 Society for the Study of Addiction.

The Work-It Study for people with arthritis: Study protocol and baseline sample characteristics.

PubMed

Keysor, Julie J; AlHeresh, Rawan; Vaughan, Molly; LaValley, Michael P; Allaire, Saralynn

2016-06-14

People with arthritis are at risk of work disability. Job accommodation and educational programs delivered before imminent work loss can minimize work disability, yet are not currently being widely implemented. The Work-It Study is a randomized controlled trial testing the efficacy of a problem solving program delivered by physical and occupational therapy practitioners to prevent work loss over a two-year period among people with arthritis and rheumatological conditions. The purpose of this paper is to describe the protocol of the randomized controlled trial, and describe the baseline characteristics of the subjects and their work outcomes. 287 participants were recruited from the Boston area in Massachusetts, USA. Eligible participants were aged between 21-65, self-reported a physicians' diagnosis of arthritis, rheumatic condition, or chronic back pain, reported a concern about working now or in the near future due to your health, worked at least 15 hours a week, had plans to continue working, and worked or lived in Massachusetts. Subjects were recruited through community sources and rheumatology offices. Participants in the experimental group received a structured interview and an education and resource packet, while participants in the control received the resource packet only. The baseline characteristics and work related outcomes of the participants were analyzed. To our knowledge, the Work-It Study is the largest and most diverse randomized controlled trial to date aiming to identify and problem solve work-related barriers, promote advocacy, and foster work disability knowledge among people with chronic disabling musculoskeletal conditions. Despite advances in medical management of arthritis and other rheumatological and musculoskeletal conditions, many people still have concerns about their ability to remain employed and are seeking strategies to help them sustain employment.

A randomized trial of diet and physical activity in women treated for stage II—IV ovarian cancer: Rationale and design of the Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES): An NRG Oncology/Gynecologic Oncology Group (GOG-225) Study☆,☆☆

PubMed Central

Thomson, Cynthia A.; Crane, Tracy E.; Miller, Austin; Garcia, David O.; Basen-Engquist, Karen; Alberts, David S.

2016-01-01

Ovarian cancer is the most common cause of gynecological cancer death in United States women. Efforts to improve progression free survival (PFS) and quality of life (QoL) after treatment for ovarian cancer are necessary. Observational studies suggest that lifestyle behaviors, including diet and physical activity, are associated with lower mortality in this population. The Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) NRG 0225 study is a randomized, controlled trial designed to test the hypothesis that a 24 month lifestyle intervention will significantly increase PFS after oncological therapy for stage II-IV ovarian cancer. Women are randomized 1:1 to a high vegetable and fiber, low-fat diet with daily physical activity goals or an attention control group. Secondary outcomes to be evaluated include QoL and gastrointestinal health. Moreover an a priori lifestyle adherence score will be used to evaluate relationships between adoption of the diet and activity goals and PFS. Blood specimens are collected at baseline, 6, 12 and 24 months for analysis of dietary adherence (carotenoids) in addition to mechanistic biomarkers (lipids, insulin, telomere length). Women are enrolled at NRG clinic sites nationally and the telephone based lifestyle intervention is delivered from The University of Arizona call center by trained health coaches. A study specific multi-modal telephone, email, and SMS behavior change software platform is utilized for information delivery, coaching and data capture. When completed, LIVES will be the largest behavior-based lifestyle intervention trial conducted among ovarian cancer survivors. PMID:27394382

Effects of prolonged and exclusive breastfeeding on child behavior and maternal adjustment: evidence from a large, randomized trial.

PubMed

Kramer, Michael S; Fombonne, Eric; Igumnov, Sergei; Vanilovich, Irina; Matush, Lidia; Mironova, Elena; Bogdanovich, Natalia; Tremblay, Richard E; Chalmers, Beverley; Zhang, Xun; Platt, Robert W

2008-03-01

The objective of this study was to assess the long-term effects of breastfeeding on child behavior and maternal adjustment. We followed up children who were in the Promotion of Breastfeeding Intervention Trial, a cluster-randomized trial of a breastfeeding promotion intervention based on the World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative. A total of 17,046 healthy, breastfeeding mother-infant pairs were enrolled from 31 Belarussian maternity hospitals and affiliated polyclinics; 13,889 (81.5%) were followed up at 6.5 years. Mothers and teachers completed the Strengths and Difficulties Questionnaire and supplemental questions bearing on internalizing and externalizing behavioral problems. Mothers also responded to questions concerning their relationships to their partner and child and their breastfeeding of subsequently born children. The experimental intervention led to a large increase in exclusive breastfeeding at 3 months (43.3% vs 6.4%) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months. No significant treatment effects were observed on either the mother or the teacher Strengths and Difficulties Questionnaire ratings of total difficulties, emotional symptoms, conduct problems, hyperactivity, peer problems, or prosocial behavior or on the supplemental behavioral questions. We found no evidence of treatment effects on the parent's marriage or on the mother's satisfaction with her relationships with her partner or child, but the experimental intervention significantly increased the duration of any breastfeeding, and mothers in the experimental group were nearly twice as likely to breastfeed exclusively the next-born child for at least 3 months. On the basis of the largest randomized trial ever conducted in the area of human lactation, we found no evidence of risks or benefits of prolonged and exclusive breastfeeding for child and maternal behavior. Breastfeeding promotion does, however, favorably affect breastfeeding of the subsequent child.

Drug-Coated Balloon Treatment of Femoropopliteal Lesions for Patients With Intermittent Claudication and Ischemic Rest Pain: 2-Year Results From the IN.PACT Global Study.

PubMed

Micari, Antonio; Brodmann, Marianne; Keirse, Koen; Peeters, Patrick; Tepe, Gunnar; Frost, Martin; Wang, Hong; Zeller, Thomas

2018-05-28

The IN.PACT Global Study is the largest prospective, multicenter, independently adjudicated trial to evaluate a paclitaxel drug-coated balloon in patients with lifestyle-limiting claudication and/or ischemic rest pain due to atherosclerotic disease of the femoropopliteal artery and includes complex lesions beyond what are typically included in randomized controlled trials. Randomized controlled trials have demonstrated the safety and efficacy of drug-coated balloons for the treatment of Trans-Atlantic Inter-Society Consensus Document II A and B lesions, but there is a need for large-scale prospective studies to evaluate a broader range of lesions. The IN.PACT Global Study enrolled 1,535 subjects, and 1,406 (1,773 lesions) were included in the pre-defined clinical cohort analysis. Freedom from clinically driven target lesion revascularization was evaluated at 24 months. The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically driven target vessel revascularization within 24 months. Mean lesion length was 12.1 cm, 35.5% were total occlusions, and 18.0% had in-stent restenosis. Freedom from clinically driven target lesion revascularization at 24 months was 83.3%, the composite safety endpoint was met in 81.7%, the 2-year all-cause mortality rate was 7.0%, and the major target limb amputation rate was 0.7%. Increased lesion length and the presence of de novo in-stent restenosis or coronary artery disease were associated with increased risk for clinically driven target lesion revascularization by 24 months. This real-world study of femoropopliteal artery disease treatment with drug-coated balloons confirmed positive findings reported from more strictly designed randomized controlled trials and showed that outcomes are durable in this population up to 2 years after treatment. (IN.PACT Global Clinical Study; NCT01609296). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2012-06-01

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

Protocol for the effect evaluation of Individual Placement and Support (IPS): a randomized controlled multicenter trial of IPS versus treatment as usual for patients with moderate to severe mental illness in Norway.

PubMed

Sveinsdottir, Vigdis; Løvvik, Camilla; Fyhn, Tonje; Monstad, Karin; Ludvigsen, Kari; Øverland, Simon; Reme, Silje Endresen

2014-11-18

Roughly one third of disability pensions in Norway are issued for mental and behavioral disorders, and vocational rehabilitation offered to this group has traditionally been dominated by train-and-place approaches with assisted or sheltered employment. Based on a more innovative place-and-train approach, Individual Placement and Support (IPS) involves supported employment in real-life competitive work settings, and has shown great promise for patients with severe mental illness. The study is a multicenter Randomized Controlled Trial (RCT) of IPS in a Norwegian context, involving an effect evaluation, a process evaluation, and a cost/benefit analysis. IPS will be compared to high quality treatment as usual (TAU), with labor market participation and educational activity at 12 months post inclusion as the primary outcome. The primary outcome will be measured using register data, and the project will also include complete follow-up up to 4 years after inclusion for long-term outcome data. Secondary outcomes include mental health status, disability and quality of life, collected through survey questionnaires at baseline, and after 6 and 12 months. Participants will include patients undergoing treatment for moderate to severe mental illness who are either unemployed or on sickness or social benefits. The estimated total sample size of 400-500 will be randomly assigned to the interventions. To be eligible, participants must have an expressed desire to work, and sufficient Norwegian reading and writing skills to fill out the questionnaires. The Effect Evaluation of Individual Placement and Support (IPS) will be one of the largest randomized controlled trials to date investigating the effectiveness of IPS on competitive employment, and the first study to evaluate the effectiveness of IPS for patients with moderate to severe mental illness within a Norwegian context. Clinicaltrials.gov: NCT01964092 . Registered October 16th, 2013.

Dismantling Multicomponent Behavioral Treatment for Insomnia in Older Adults: A Randomized Controlled Trial

PubMed Central

Epstein, Dana R.; Sidani, Souraya; Bootzin, Richard R.; Belyea, Michael J.

2012-01-01

Study Objective: Recently, the use of multicomponent insomnia treatment has increased. This study compares the effect of single component and multicomponent behavioral treatments for insomnia in older adults after intervention and at 3 months and 1 yr posttreatment. Design: A randomized, controlled study. Setting: Veterans Affairs medical center. Participants: 179 older adults (mean age, 68.9 yr ± 8.0; 115 women [64.2%]) with chronic primary insomnia. Interventions: Participants were randomly assigned to 6 wk of stimulus control therapy (SCT), sleep restriction therapy (SRT), the 2 therapies combined into a multicomponent intervention (MCI), or a wait-list control group. Measurements and Results: Primary outcomes were subjective (daily sleep diary) and objective (actigraphy) measures of sleep-onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TIB), and sleep efficiency (SE). Secondary outcomes were clinical measures including response and remission rates. There were no differences between the single and multicomponent interventions on primary sleep outcomes measured by diary and actigraphy. All treatments produced significant improvement in diary-reported sleep in comparison with the control group. Effect sizes for sleep diary outcomes were medium to large. Treatment gains were maintained at follow-up for diary and actigraph measured SOL, WASO, and SE. The MCI group had the largest proportion of treatment remitters. Conclusions: For older adults with chronic primary insomnia, the findings provide initial evidence that SCT, SRT, and MCI are equally efficacious and produce sustainable treatment gains on diary, actigraphy, and clinical outcomes. From a clinical perspective, MCI may be a preferred treatment due to its higher remission rate. Clinical Trial Information: Behavioral Intervention for Insomnia in Older Adults. NCT01154023. URL: http://clinicaltrials.gov/ct2/show/NCT01154023?term=Behavioral+Intervention+for+Insomnia+in+Older+Adults&rank=1. Citation: Epstein DR; Sidani S; Bootzin RR; Belyea MJ. Dismantling multicomponent behavioral treatment for insomnia in older adults: a randomized controlled trial. SLEEP 2012;35(6):797-805. PMID:22654199

Abelmoschus manihot - a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial.

PubMed

Li, Ping; Chen, Yi-Zhi; Lin, Hong-Li; Ni, Zhao-Hui; Zhan, Yong-Li; Wang, Rong; Yang, Hong-Tao; Fang, Jing-Ai; Wang, Nian-Song; Li, Wen-Ge; Sun, Xue-Feng; Chen, Xiang-Mei

2017-04-11

IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. ClinicalTrials.gov, identifier: NCT02231125 . Registered on 30 August 2014.

Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial (SPRINT)

PubMed Central

Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

2016-01-01

Background The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter, randomized clinical trial of 9,361 participants with hypertension who are ≥ 50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal <120 mm Hg) compared to standard control (systolic blood pressure goal <140 mm Hg) on cardiovascular events using commonly prescribed antihypertensive medications and lifestyle modification. Objective To describe the recruitment strategies and lessons learned during recruitment of the SPRINT cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥ 75 years, women, and minorities. Methods In collaboration with the National Institutes of Health Project Office and SPRINT Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began November 8, 2010 and ended March 15, 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Results Recruitment was scheduled to last 24 months to enroll a target of 9,250 participants; in just over 28 months, the trial enrolled 9,361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by SPRINT staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized /number screened) was 64% (9,361 randomized /14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those age ≥ 75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional clinics were included and inclusion criteria were broadened, keeping event rates and trial power in mind. As overall recruitment improved, a greater focus on subgroup recruitment was implemented. Conclusion SPRINT met its overall projected recruitment goal by using diverse, locally adapted enrollment strategies to specifically target persons with cardiovascular disease, chronic kidney disease, ≥ 75 year old, women, and minority subgroups. The trial exceeded its recruitment goal for minorities but found it a challenge to meet the competing demands of the targeted goals for recruiting into the remaining four subgroups. Important lessons include the imperative to monitor the recruitment process carefully, decide early to add new clinics or modify inclusion and exclusion criteria if recruitment lags, and consider limiting enrollment to subgroups only. We found benefit in using multiple recruitment sources simultaneously; mass mailing produced the largest number of participants, but referrals resulted in the greater randomization yield. PMID:26911833

The effect of atrial-based pacing on exercise capacity as measured by the 6-minute walk test: a substudy of the Canadian Trial of Physiological Pacing (CTOPP).

PubMed

Baranchuk, Adrian; Healey, Jeff S; Thorpe, Kevin E; Morillo, Carlos A; Nair, Girish; Crystal, Eugene; Kerr, Charles R; Connolly, Stuart J

2007-08-01

Although several randomized trials have detected no reduction in major cardiovascular events with the routine use of dual-chamber as opposed to ventricular pacemakers, many individuals continue to advocate their use as a means of improving exercise capacity. The Canadian Trial of Physiological Pacing (CTOPP) trial is the largest trial comparing ventricular pacing to atrial-based pacing (atrial or dual-chamber) in patients with bradycardia. All patients in this trial were asked to complete a 6-minute hall walk test (6MWT) at the time of their first study follow-up. The distance walked in 6 minutes and the patient's heart rate before and immediately after the walk were recorded. Of the 2568 patients in the CTOPP, 76% completed the 6MWT. The mean distance walked was 350 +/- 127 m in the ventricular pacing group and 356 +/- 127 m in the atrial-based group (P = NS). Similarly, there was no difference in the change in heart rate between the two groups (17 +/- 13 vs. 18 +/- 12 bpm: P = NS). However, among patients with an unpaced heart rate of

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734. PMID:22463698

Randomized trials published in some Chinese journals: how many are randomized?

PubMed

Wu, Taixiang; Li, Youping; Bian, Zhaoxiang; Liu, Guanjian; Moher, David

2009-07-02

The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports, including many studies identified by their authors as randomized controlled trials. It has been noticed that these reports mostly present positive results, and their quality and authenticity have consequently been called into question. We investigated the adequacy of randomization of clinical trials published in recent years in China to determine how many of them met acceptable standards for allocating participants to treatment groups. The China National Knowledge Infrastructure electronic database was searched for reports of randomized controlled trials on 20 common diseases published from January 1994 to June 2005. From this sample, a subset of trials that appeared to have used randomization methods was selected. Twenty-one investigators trained in the relevant knowledge, communication skills and quality control issues interviewed the original authors of these trials about the participant randomization methods and related quality-control features of their trials. From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure database, we found 3137 apparent randomized controlled trials. Of these, 1452 were studies of conventional medicine (published in 411 journals) and 1685 were studies of traditional Chinese medicine (published in 352 journals). Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for randomization and could on those grounds be deemed authentic randomized controlled trials (6.8%, 95% confidence interval 5.9-7.7). There was no statistically significant difference in the rate of authenticity between randomized controlled trials of traditional interventions and those of conventional interventions. Randomized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals (relative risk 1.58, 95% confidence interval 1.18-2.13, and relative risk 14.42, 95% confidence interval 9.40-22.10, respectively). The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals (relative risk 9.32, 95% confidence interval 5.83-14.89). All randomized controlled trials of pre-market drug clinical trial were authentic by our criteria. Of the trials conducted at university-affiliated hospitals, 56.3% were authentic (95% confidence interval 32.0-81.0). Most reports of randomized controlled trials published in some Chinese journals lacked an adequate description of randomization. Similarly, most so called 'randomized controlled trials' were not real randomized controlled trials owing to a lack of adequate understanding on the part of the authors of rigorous clinical trial design. All randomized controlled trials of pre-market drug clinical trial included in this research were authentic. Randomized controlled trials conducted by authors in high level hospitals, especially in hospitals affiliated to medical universities had a higher rate of authenticity. That so many non-randomized controlled trials were published as randomized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed.

Randomized trials published in some Chinese journals: how many are randomized?

PubMed Central

Wu, Taixiang; Li, Youping; Bian, Zhaoxiang; Liu, Guanjian; Moher, David

2009-01-01

Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports, including many studies identified by their authors as randomized controlled trials. It has been noticed that these reports mostly present positive results, and their quality and authenticity have consequently been called into question. We investigated the adequacy of randomization of clinical trials published in recent years in China to determine how many of them met acceptable standards for allocating participants to treatment groups. Methods The China National Knowledge Infrastructure electronic database was searched for reports of randomized controlled trials on 20 common diseases published from January 1994 to June 2005. From this sample, a subset of trials that appeared to have used randomization methods was selected. Twenty-one investigators trained in the relevant knowledge, communication skills and quality control issues interviewed the original authors of these trials about the participant randomization methods and related quality-control features of their trials. Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure database, we found 3137 apparent randomized controlled trials. Of these, 1452 were studies of conventional medicine (published in 411 journals) and 1685 were studies of traditional Chinese medicine (published in 352 journals). Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for randomization and could on those grounds be deemed authentic randomized controlled trials (6.8%, 95% confidence interval 5.9–7.7). There was no statistically significant difference in the rate of authenticity between randomized controlled trials of traditional interventions and those of conventional interventions. Randomized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals (relative risk 1.58, 95% confidence interval 1.18–2.13, and relative risk 14.42, 95% confidence interval 9.40–22.10, respectively). The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals (relative risk 9.32, 95% confidence interval 5.83–14.89). All randomized controlled trials of pre-market drug clinical trial were authentic by our criteria. Of the trials conducted at university-affiliated hospitals, 56.3% were authentic (95% confidence interval 32.0–81.0). Conclusion Most reports of randomized controlled trials published in some Chinese journals lacked an adequate description of randomization. Similarly, most so called 'randomized controlled trials' were not real randomized controlled trials owing toa lack of adequate understanding on the part of the authors of rigorous clinical trial design. All randomized controlled trials of pre-market drug clinical trial included in this research were authentic. Randomized controlled trials conducted by authors in high level hospitals, especially in hospitals affiliated to medical universities had a higher rate of authenticity. That so many non-randomized controlled trials were published as randomized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed. PMID:19573242

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

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

Protocol for the Cognitive Interventions and Nutritional Supplements (CINS) trial: A randomized controlled multicenter trial of a brief intervention (BI) versus a BI plus cognitive behavioral treatment (CBT) versus nutritional supplements for patients with long-lasting muscle and back pain

PubMed Central

2011-01-01

Abstract Background Brief intervention programs are clinically beneficial, and cost efficient treatments for low back pain, when offered at 8-12 weeks, compared with treatment as usual. However, about 30% of the patients do not return to work. The European Guidelines for treatment of chronic low back pain recommends Cognitive Behavioral Therapy (CBT), but conclude that further research is needed to evaluate the effectiveness of CBT for chronic low back pain. Methods/Design The aim of the multicenter CINS trial (Cognitive Interventions and Nutritional Supplements) is to compare the effectiveness of 4 different interventions; Brief Intervention, Brief Intervention and CBT, Brief Intervention and nutritional supplements of seal oil, and Brief Intervention and nutritional supplements of soy oil. All participants will be randomly assigned to the interventions. The nutritional supplements will be tested in a double blind design. 400 patients will be recruited from a population of chronic low back pain patients that have been sick listed for 2-10 months. Four outpatient clinics, located in different parts of Norway, will participate in recruitment and treatment of the patients. The Brief Intervention is a one session cognitive, clinical examination program based on a non-injury model, where return to normal activity and work is the main goal, and is followed by two booster sessions. The CBT is a tailored treatment involving 7 sessions, following a detailed manual. The nutritional supplements consist of a dosage of 10 grams of either soy or seal oil (capsules) per day for 3 months, administered in a double blind design. All patients will be followed up with questionnaires after 3, 6 and 12 months, while sick leave data will be collected up to at least 24 months after randomization. The primary outcome of the study is sick leave and will be based on register data from the National Insurance Administration. Secondary outcomes include self-reported data on disability, pain, and psychological variables. Conclusions To our knowledge, the CINS trial will be the largest, randomized trial of psychological and nutritional interventions for chronic low back pain patients to date. It will provide important information regarding the effectiveness of CBT and seal oil for chronic low back pain patients. Trial Registration http://www.clinicaltrials.gov, with registration number NCT00463970. PMID:21736730

Low-fat dietary pattern intervention and health-related quality of life: The WHI randomized controlled Dietary Modification trial

PubMed Central

Assaf, Annlouise R.; Beresford, Shirley A.A.; Risica, Patricia Markham; Aragaki, Aaron; Brunner, Robert L.; Bowen, Deborah J.; Naughton, Michelle; Rosal, Milagros C.; Snetselaar, Linda; Wenger, Nanette

2015-01-01

Background Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women’s Health Initiative (WHI) Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention. Objective To evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depressive symptoms, cognitive functioning, and sleep quality. Design Randomized controlled trial was analyzed as intent to treat. Participants Between 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline ≥32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type-1 diabetes, medical conditions with predicted survival less than three years. Intervention Goals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter. Main Outcome Measures RAND 36-Item Health Survey was used to assess HRQoL at baseline, year 1, and close-out (about 8 years post randomization), and estimate differential HRQoL subscale change scores. Statistical analysis performed Mean change in HRQoL scores (year 1 minus baseline) were compared by randomization group using linear models. Results At one year, there was a differential change between intervention and comparison group of 1.7 units (1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (1.7, 2.3), vitality by 1.9 units (1.6, 2.2), and global QOL by 0.09 units (0.07, 0.12). With the exception of global QOL, these effects were significantly modified by BMI at baseline. Conclusions DM intervention was associated with small, but significant improvements in three health related quality of life subscales: general health, physical functioning, and vitality at one year follow-up, with the largest improvements seen in the women with the greatest baseline BMI. PMID:26384466

Randomized controlled trial of probiotics to reduce common cold in schoolchildren.

PubMed

Rerksuppaphol, Sanguansak; Rerksuppaphol, Lakkana

2012-10-01

The common cold is responsible for the largest proportion of school and work absenteeism and causes a huge economic burden. None of the current interventions is greatly effective for prevention. Our aim was to assess the efficacy of a two-strain combination probiotic for prevention of common cold symptoms in healthy schoolchildren. A double-blind randomized controlled trial was performed during the winter season in a public school of central Thailand. Children, aged 8-13 years, were randomized to receive either a two-strain combination probiotic (Lactobacillus acidophilus and Bifidobacterium bifidum) or placebo given twice a day for 3 months. The primary outcome was any symptom of cold during the 3-month study period while vomiting, diarrhea, use of antibiotics, school absence due to any cause, school absence due to cold and duration of all symptoms were secondary outcomes. Of the 40 children in each group, 31 (77%) in the probiotic group, compared to 38 (95%) in the placebo group (P= 0.048), developed at least one symptom of cold. Children in the probiotics group had significantly lower risk of fever, cough, rhinorrhea, school absence and school absence related to common cold compared to children in the placebo group. There was no impact on diarrhea and vomiting. A two-strain probiotic combination given twice a day for 3 months was able to reduce the symptoms of the common cold and school absenteeism in schoolchildren. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

The Effects of Quality Improvement for Depression in Primary Care at Nine Years: Results from a Randomized, Controlled Group-Level Trial

PubMed Central

Wells, Kenneth B; Tang, Lingqi; Miranda, Jeanne; Benjamin, Bernadette; Duan, Naihua; Sherbourne, Cathy D

2008-01-01

Objective To examine 9-year outcomes of implementation of short-term quality improvement (QI) programs for depression in primary care. Data Sources Depressed primary care patients from six U.S. health care organizations. Study Design Group-level, randomized controlled trial. Data Collection Patients were randomly assigned to short-term QI programs supporting education and resources for medication management (QI-Meds) or access to evidence-based psychotherapy (QI-Therapy); and usual care (UC). Of 1,088 eligible patients, 805 (74 percent) completed 9-year follow-up; results were extrapolated to 1,269 initially enrolled and living. Outcomes were psychological well-being (Mental Health Inventory, five-item version [MHI5]), unmet need, services use, and intermediate outcomes. Principal Findings At 9 years, there were no overall intervention status effects on MHI5 or unmet need (largest F (2,41)=2.34, p=.11), but relative to UC, QI-Meds worsened MHI5, reduced effectiveness of coping and among whites lowered tangible social support (smallest t(42)=2.02, p=.05). The interventions reduced outpatient visits and increased perceived barriers to care among whites, but reduced attitudinal barriers due to racial discrimination and other factors among minorities (smallest F (2,41)=3.89, p=.03). Conclusions Main intervention effects were over but the results suggest some unintended negative consequences at 9 years particularly for the medication-resource intervention and shifts to greater perceived barriers among whites yet reduced attitudinal barriers among minorities. PMID:18522664

[Methodologies of publications in the Revista de Investigación Clínica during the last 20 years].

PubMed

López-Jiménez, F; Borovoy, J

1997-01-01

To characterize the clinical research methods published in the Revista de Investigación Clínica for the past 20 years. Comparative study of methods used in the RIC articles published in 3-years periods representing three decades (1972-74, 1982-84, 1992-94). Out of 273 original papers, 218 (80%) were of clinical research. There was an increased percentage of longitudinal vs cross-sectional studies, with cohort and randomized clinical trials showing the largest increase. The total number of research manuscripts also increased. The clinical research methods of the papers in the RIC have shown an increased rate of designs with a higher scientific value.

Preventing smoking initiation or relapse following 8.5 weeks of involuntary smoking abstinence in basic military training: trial design, interventions, and baseline data.

PubMed

Brandon, Thomas H; Klesges, Robert C; Ebbert, Jon O; Talcott, Gerald W; Thomas, Fridtjof; Leroy, Karen; Richey, Phyllis A; Colvin, Lauren

2014-05-01

Smoking cessation is a primary method of reducing excess mortality and morbidity. Unfortunately, the vast majority of cessation attempts end in eventual relapse. Relapse-prevention interventions have shown some success at improving the long-term maintenance of tobacco abstinence among individuals motivated to abstain. However, involuntary tobacco abstinence (e.g., military training, hospitalization, incarceration) presents another opportunity for intervention to prevent relapse. During basic military training (BMT), tobacco use is strictly forbidden in all service branches, but tobacco relapse (and initiation) following BMT is extremely high. This paper reports on the design, intervention development, and baseline characteristics of a randomized controlled trial testing minimal interventions designed to prevent tobacco relapse among United States Air Force (USAF) personnel following BMT. Participants are randomized by squadron to receive either a standard smoking-cessation booklet, a new motivation-based booklet designed specifically for USAF personal, or the latter booklet combined with a brief, face-to-face motivational session. Primary outcomes will be self-reported tobacco use at 12 and 24month follow-up. Given that the Department of Defense is the world's largest employer, the potential of leveraging involuntary tobacco abstinence during BMT into extended abstinence has substantial public health significance. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of Early Head Start on child welfare system involvement: A first look at longitudinal child maltreatment outcomes☆

PubMed Central

Green, Beth L.; Ayoub, Catherine; Bartlett, Jessica Dym; Von Ende, Adam; Furrer, Carrie; Chazan-Cohen, Rachel; Vallotton, Claire; Klevens, Joanne

2015-01-01

The high societal and personal costs of child maltreatment make identification of effective early prevention programs a high research priority. Early Head Start (EHS), a dual generational program serving low-income families with children prenatally through age three years, is one of the largest federally funded programs for infants and toddlers in the United States. A national randomized trial found EHS to be effective in improving parent and child outcomes, but its effectiveness in reducing child maltreatment was not assessed. The current study used administrative data from state child welfare agencies to examine the impact of EHS on documented abuse and neglect among children from seven of the original seventeen programs in the national EHS randomized controlled trial. Results indicated that children in EHS had significantly fewer child welfare encounters between the ages of five and nine years than did children in the control group, and that EHS slowed the rate of subsequent encounters. Additionally, compared to children in the control group, children in EHS were less likely to have a substantiated report of physical or sexual abuse, but more likely to have a substantiated report of neglect. These findings suggest that EHS may be effective in reducing child maltreatment among low-income children, in particular, physical and sexual abuse. PMID:26744550

Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

PubMed Central

Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

2011-01-01

Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

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.

Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk

PubMed Central

Inzucchi, Silvio E.; Lachin, John M.; Wanner, Christoph; Fitchett, David; Kohler, Sven; Mattheus, Michaela; Woerle, Hans J.; Broedl, Uli C.; Johansen, Odd Erik; Albers, Gregory W.; Diener, Hans Christoph

2017-01-01

Background and Purpose— In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89–1.56; P=0.26). We further investigated cerebrovascular events. Methods— Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. Results— The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81–1.45; P=0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. Conclusions— In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676. PMID:28386035

Psychosocial Treatment Efficacy for Disruptive Behavior Problems in Very Young Children: A Meta-Analytic Examination

PubMed Central

Comer, Jonathan S.; Chow, Candice; Chan, Priscilla T.; Cooper-Vince, Christine; Wilson, Lianna A.S.

2012-01-01

Objective Service use trends showing increased off-label prescribing in very young children and reduced psychotherapy use raise concerns about quality of care for early disruptive behavior problems. Meta-analysis can empirically clarify best practices and guide clinical decision making by providing a quantitative synthesis of a body of literature, identifying the magnitude of overall effects across studies, and determining systematic factors associated with effect variations. Method We used random-effects meta-analytic procedures to empirically evaluate the overall effect of psychosocial treatments on early disruptive behavior problems, as well as potential moderators of treatment response. Thirty-six controlled trials, evaluating 3,042 children, met selection criteria (mean sample age, 4.7 years; 72.0% male; 33.1% minority youth). Results Psychosocial treatments collectively demonstrated a large and sustained effect on early disruptive behavior problems (Hedges’ g = 0.82), with the largest effects associated with behavioral treatments (Hedges’ g = 0.88), samples with higher proportions of older and male youth, and comparisons against treatment as usual (Hedges’ g = 1.17). Across trials, effects were largest for general externalizing problems (Hedges’ g =0.90) and problems of oppositionality and noncompliance (Hedges’ g = 0.76), and were weakest, relatively speaking, for problems of impulsivity and hyperactivity (Hedges’ g = 0.61). Conclusions In the absence of controlled trials evaluating psychotropic interventions, findings provide robust quantitative support that psychosocial treatments should constitute first-line treatment for early disruptive behavior problems. Against a backdrop of concerning trends in the availability and use of supported interventions, findings underscore the urgency of improving dissemination efforts for supported psychosocial treatment options, and removing systematic barriers to psychosocial care for affected youth. PMID:23265631

Systematic review of pelvic floor interventions during pregnancy.

PubMed

Schreiner, Lucas; Crivelatti, Isabel; de Oliveira, Julia M; Nygaard, Christiana C; Dos Santos, Thais G

2018-04-28

Pelvic floor interventions during pregnancy could reduce the impact of pregnancy and delivery on the pelvic floor. To determine the effects of pelvic floor interventions during pregnancy on childbirth-related and pelvic floor parameters. PubMed, Embase, and LILACS were searched for reports published during between 1990 and 2016 in English, Spanish, or Portuguese. The search terms were "pregnancy," "pelvic floor muscle training," and related terms. Randomized controlled trials with healthy pregnant women were included. Baseline and outcome data (childbirth-related parameters, pelvic floor symptoms) were compared for three interventions: EPI-NO (Tecsana, Munich, Germany) perineal dilator, pelvic floor muscle training, and perineal massage. A total of 22 trials were included. Two of three papers assessing EPI-NO showed no benefit. The largest study investigating pelvic floor muscle training reported a significant reduction in the duration of the second stage of labor (P<0.01), and this intervention also reduced the incidence of urinary incontinence (evaluated in 10 trials). Two of six trials investigating perineal massage reported that a lower rate of perineal pain was associated with this intervention. Pelvic floor muscle training and perineal massage improved childbirth-related parameters and pelvic floor symptoms, whereas EPI-NO showed no benefit. © 2018 International Federation of Gynecology and Obstetrics.

Are Age-Related Differences Uniform Across Different Inhibitory Functions?

PubMed

Vadaga, Kiran K; Blair, Mervin; Li, Karen Z H

2016-07-01

In the current experiment, we examined the relative age-sensitivity of 3 inhibitory functions: access, deletion, and restraint by taking into consideration their underlying control processes: proactive and reactive control. The 3 inhibitory functions were measured using a sequential flanker task. Young (age: 18-35, n = 24) and older adults (age: 60-75, n = 25) first memorized a series of 8 animal words in a fixed order. In the test phase, these stimuli were presented randomly either singly or with flankers and participants responded "yes" or "no" based on the prelearned sequence. In the access trials, flankers were either ahead of the current target or unrelated. In the deletion trials, flankers were previous target items. In the restraint trials, the flanker cues (XXXX) prompted the participants to withhold responses occasionally. Unflanked trials served as the baseline condition. Age-related differences in the magnitude of inhibition effects were largest in restraint, followed by deletion. No age-related differences were observed in access. Our findings suggest that the magnitude of age-related differences in inhibitory functions is contingent on the degree of proactive control recruited by a given inhibitory function. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HYPERTENSION IMPROVEMENT PROJECT (HIP): RANDOMIZED TRIAL OF QUALITY IMPROVEMENT FOR PHYSICIANS AND LIFESTYLE MODIFICATION FOR PATIENTS

PubMed Central

Svetkey, Laura P.; Pollak, Kathryn I.; Yancy, William S.; Dolor, Rowena J.; Batch, Bryan C.; Samsa, Greg; Matchar, David B.; Lin, Pao-Hwa

2009-01-01

Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients, blood pressure control rates remain low. In community-based primary care clinics, we performed a nested, 2×2 randomized, controlled trial of physician intervention vs. control and/or patient intervention vs. control. Physician Intervention included internet-based training, self-monitoring, and quarterly feedback reports. Patient Intervention included 20 weekly group sessions followed by 12 monthly phone counseling contacts, and focused on weight loss, DASH dietary pattern, exercise, and reduced sodium intake. The primary outcome was change in systolic blood pressure at 6 months. Eight primary care practices (32 physicians) were randomized to Physician Intervention or Control. Within those practices, 574 patients were randomized to Patient Intervention or Control. Patients’ mean age was 60 years, 61% female, 37% African American. BP data were available for 91% of patients at 6 months. The main effect of Physician Intervention on systolic blood pressure at 6 months, adjusted for baseline pressure, was 0.3 mmHg (95% CI −1.5 to 2.2; p = 0.72). The main effect of the Patient Intervention was −2.6 mmHg (95% CI −4.4, −0.7; p = 0.01). The interaction of the 2 interventions was significant (p = 0.03); the largest impact was observed with the combination of Physician and Patient Intervention (−9.7 ± 12.7 mmHg). Differences between treatment groups did not persist at 18 months. Combined physician and patient intervention lowers blood pressure; future research should focus on enhancing effectiveness and sustainability of these interventions. PMID:19920081

Exercise training for blood pressure: a systematic review and meta-analysis.

PubMed

Cornelissen, Veronique A; Smart, Neil A

2013-02-01

We conducted meta-analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes. Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to February 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (SBP) was reduced after endurance (-3.5 mm Hg [confidence limits -4.6 to -2.3]), dynamic resistance (-1.8 mm Hg [-3.7 to -0.011]), and isometric resistance (-10.9 mm Hg [-14.5 to -7.4]) but not after combined training. Reductions in diastolic BP (DBP) were observed after endurance (-2.5 mm Hg [-3.2 to -1.7]), dynamic resistance (-3.2 mm Hg [-4.5 to -2.0]), isometric resistance (-6.2 mm Hg [-10.3 to -2.0]), and combined (-2.2 mm Hg [-3.9 to -0.48]) training. BP reductions after endurance training were greater (P<0.0001) in 26 study groups of hypertensive subjects (-8.3 [-10.7 to -6.0]/-5.2 [-6.8 to -3.4] mm Hg) than in 50 groups of prehypertensive subjects (-2.1 [-3.3 to -0.83]/-1.7 [-2.7 to -0.68]) and 29 groups of subjects with normal BP levels (-0.75 [-2.2 to +0.69]/-1.1 [-2.2 to -0.068]). BP reductions after dynamic resistance training were largest for prehypertensive participants (-4.0 [-7.4 to -0.5]/-3.8 [-5.7 to -1.9] mm Hg) compared with patients with hypertension or normal BP. Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in SBP.

Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis – an Assessor and Statistician Blinded Randomized Controlled Trial

PubMed Central

Parent, Eric C.; Khodayari Moez, Elham; Hedden, Douglas M.; Hill, Douglas L.; Moreau, Marc; Lou, Edmond; Watkins, Elise M.; Southon, Sarah C.

2016-01-01

Background The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis. Objectives To determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS. Methods Fifty patients with AIS aged 10–18 years, with curves of 10°-45° and Risser grade 0–5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30–45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported. Results In the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5°, 95% CI -1.1° to -5.9°, p = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40°, (95% CI -0.03° to -0.8°, p = 0.046), suggesting that an average patient with 51.2° at baseline, will have a 49.3° Sum of Curves at six months in the Schroth group, and 55.1° in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1° (95% CI -1.7° to -6.5°, p = 0.002) and Sum of Curves=−0.5° (95% CI -0.8 to 0.2, p = 0.006). Conclusion Schroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS. Trial Registration NCT01610908 PMID:28033399

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.

Revisiting sample size: are big trials the answer?

PubMed

Lurati Buse, Giovanna A L; Botto, Fernando; Devereaux, P J

2012-07-18

The superiority of the evidence generated in randomized controlled trials over observational data is not only conditional to randomization. Randomized controlled trials require proper design and implementation to provide a reliable effect estimate. Adequate random sequence generation, allocation implementation, analyses based on the intention-to-treat principle, and sufficient power are crucial to the quality of a randomized controlled trial. Power, or the probability of the trial to detect a difference when a real difference between treatments exists, strongly depends on sample size. The quality of orthopaedic randomized controlled trials is frequently threatened by a limited sample size. This paper reviews basic concepts and pitfalls in sample-size estimation and focuses on the importance of large trials in the generation of valid evidence.

Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.

PubMed

Isaacson, R S; Haynes, N; Seifan, A; Larsen, D; Christiansen, S; Berger, J C; Safdieh, J E; Lunde, A M; Luo, A; Kramps, M; McInnis, M; Ochner, C N

2014-01-01

Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). Observational. Online. Men/Women, aged 25+, recruited via facebook.com. Alzheimer's Universe (www.AlzU.org) education research platform. Pre/post-test performance, self-reported Likert-scale ratings, completion rates. Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.

Clinical, metabolic and psychological outcomes and treatment costs of a prospective randomized trial based on different educational strategies to improve diabetes care (PRODIACOR).

PubMed

Gagliardino, J J; Lapertosa, S; Pfirter, G; Villagra, M; Caporale, J E; Gonzalez, C D; Elgart, J; González, L; Cernadas, C; Rucci, E; Clark, C

2013-09-01

To evaluate the effect of system interventions (formalized data collection and 100% coverage of medications and supplies) combined with physician and/or patient education on therapeutic indicators and costs in Type 2 diabetes. This was a randomized 2 × 2 design in public health, social security or private prepaid primary care clinics in Corrientes, Argentina. Thirty-six general practitioners and 468 adults with Type 2 diabetes participated. Patients of nine participating physicians were selected randomly and assigned to one of four structured group education programmes (117 patients each): control (group 1), physician education (group 2), patient education (group 3), and both physician education and patient education (group 4), with identical system interventions in all four groups. Outcome measures included HbA(1c), BMI, blood pressure, fasting glucose, lipid profile, drug consumption, resource use and patient well-being at baseline and every 6 months up to 42 months. HbA(1c) decreased significantly from 4 mmol/mol to 10 mmol/mol by 42 months (P < 0.05); the largest and more consistent decrease was in the groups where patients and physicians were educated. Blood pressure and triglycerides decreased significantly in all groups; the largest changes were recorded in the combined education group. The World Health Organization-5 Lowe score showed significant improvements, without differences among groups. The lowest treatment cost was seen in the combined education group. In a primary care setting, educational interventions combined with comprehensive care coverage resulted in long-term improvement in clinical, metabolic and psychological outcomes at the best cost-effectiveness ratio. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

PubMed

Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

2017-12-01

Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance level, the sample size was calculated to be 35 providers in each group, which includes an 11% lost to follow-up of chiropractors and 20% of patient visits. This study will be the first direct comparison of adverse event reporting using passive versus active surveillance. It is also the largest prospective evaluation of adverse events reported after chiropractic manual therapy in children, identified as a major gap in the academic literature. ClinicalTrials.gov, ID: NCT02268331 . Registered on 10 October 2014.

Obstetric and perinatal outcome of babies born from sperm selected by MACS from a randomized controlled trial.

PubMed

Romany, Laura; Garrido, Nicolas; Cobo, Ana; Aparicio-Ruiz, Belen; Serra, Vicente; Meseguer, Marcos

2017-02-01

The purpose of this study is to assess outcomes after magnetic-activated cell sorting (MACS) technology on obstetric and perinatal outcomes compared with those achieved after swim up from randomized controlled trial. This is a two-arm, unicentric, prospective, randomized, and triple-blinded trial and has a total of 237 infertile couples, between October 2010 and January 2013. A total of 65 and 66 newborns from MACS and control group, respectively, were described. MACS had no clinically relevant adverse effects on obstetric and perinatal outcomes. No differences were found for obstetric problems including premature rupture of membranes 6.1% (CI95% 0-12.8) vs. 5.9% (CI95% 0-12.4), 1st trimester bleeding 28.6% (CI95% 15.9-41.2) vs. 23.5% (CI95% 11.9-35.1), invasive procedures as amniocentesis 2.0% (CI95% 0-5.9) vs. 3.9% (CI95% 0-9.2), diabetes 14.3% (CI95% 4.5-24.1) vs. 9.8% (CI95% 1.6-17.9), anemia 6.1% (CI95% 0-12.8) vs. 5.9%(CI95% 0-12.4), 2nd and 3rd trimesters 10.2% (CI95% 1.7-18.7) vs. 5.9% (CI95% 0-12.4), urinary tract infection 8.2% (CI95% 0.5-15.9) vs. 3.9% (CI95% 0-9.2), pregnancy-induced hypertension 6.1% (CI95% 0-12.8) vs. 15.7% (CI95% 5.7-25.7), birth weight (g) 2684.10 (CI95% 2499.48-2868.72) vs. 2676.12 (CI95% 2499.02-2852.21), neonatal height (cm) 48.3 (CI95% 47.1-49.4) vs. 46.5 (CI95% 44.6-48.4), and gestational cholestasis 0%(CI95% 0-0) vs. 3.9% (CI95% 0-9.2), respectively, in MACS group compared with control group. Our data suggest that MACS technology does not increase or decrease Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation adverse obstetric and perinatal outcomes in children conceived when this technology was performed, being the largest randomized control trial with live birth reported results with MACS.

Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial.

PubMed

Chandra, Alvin; Lewis, Eldrin F; Claggett, Brian L; Desai, Akshay S; Packer, Milton; Zile, Michael R; Swedberg, Karl; Rouleau, Jean L; Shi, Victor C; Lefkowitz, Martin P; Katova, Tzvetana; McMurray, John J V; Solomon, Scott D

2018-04-04

Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). To examine the effects of sacubitril/valsartan on physical and social activities. The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. Sacubitril/valsartan, 200 mg twice daily, or enalapril, 10 mg twice daily. Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95% CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95% CI, 0.78-2.60], P < .001; and 2.36 [95% CI, 1.01-3.71], P = .001, respectively). In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients. clinicaltrials.gov Identifier: NCT01035255.

Use of Theory in Behavior Change Interventions.

PubMed

Bluethmann, Shirley M; Bartholomew, L Kay; Murphy, Caitlin C; Vernon, Sally W

2017-04-01

Theory use may enhance effectiveness of behavioral interventions, yet critics question whether theory-based interventions have been sufficiently scrutinized. This study applied a framework to evaluate theory use in physical activity interventions for breast cancer survivors. The aims were to (1) evaluate theory application intensity and (2) assess the association between extensiveness of theory use and intervention effectiveness. Studies were previously identified through a systematic search, including only randomized controlled trials published from 2005 to 2013, that addressed physical activity behavior change and studied survivors who were <5 years posttreatment. Eight theory items from Michie and Prestwich's coding framework were selected to calculate theory intensity scores. Studies were classified into three subgroups based on extensiveness of theory use (Level 1 = sparse; Level 2 = moderate; and Level 3 = extensive). Fourteen randomized controlled trials met search criteria. Most trials used the transtheoretical model ( n = 5) or social cognitive theory ( n = 3). For extensiveness of theory use, 5 studies were classified as Level 1, 4 as Level 2, and 5 as Level 3. Studies in the extensive group (Level 3) had the largest overall effect size ( g = 0.76). Effects were more modest in Level 1 and 2 groups with overall effect sizes of g = 0.28 and g = 0.36, respectively. Theory use is often viewed as essential to behavior change, but theory application varies widely. In this study, there was some evidence to suggest that extensiveness of theory use enhanced intervention effectiveness. However, there is more to learn about how theory can improve interventions for breast cancer survivors.

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.

Entrepreneurship education: A strength-based approach to substance use and suicide prevention for American Indian adolescents.

PubMed

Tingey, Lauren; Larzelere-Hinton, Francene; Goklish, Novalene; Ingalls, Allison; Craft, Todd; Sprengeler, Feather; McGuire, Courtney; Barlow, Allison

2016-01-01

American Indian (AI) adolescents suffer the largest disparities in substance use and suicide. Predominating prevention models focus primarily on risk and utilize deficit-based approaches. The fields of substance use and suicide prevention research urge for positive youth development frameworks that are strength based and target change at individual and community levels. Entrepreneurship education is an innovative approach that reflects the gap in available programs. This paper describes the development and evaluation of a youth entrepreneurship education program in partnership with one AI community. We detail the curriculum, process evaluation results, and the randomized controlled trial evaluating its efficacy for increasing protective factors. Lessons learned may be applicable to other AI communities.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

PubMed

Gresham, Gillian K; Ehrhardt, Stephan; Meinert, Jill L; Appel, Lawrence J; Meinert, Curtis L

2018-02-01

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted. The objective of this analysis was to describe characteristics and trends of clinical trials funded by the National Institutes of Health over time and by Institutes and Centers of the National Institutes of Health. Methods Interventional studies funded by the National Institutes of Health and registered in ClinicalTrials.gov between 2005 and 2015 were included in the analysis. Trials were identified from the 27 March 2016 Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database. A descriptive analysis of trials by year and National Institutes of Health Institute/Center was performed. Results There were 12,987 National Institutes of Health-funded clinical trials registered between 2005 and 2015. There were 1,580, 1,116, and 930 trials registered in 2005, 2010, and 2015, respectively. The majority were early-development trials (phases 0, 1, or 2; 53%), randomized (61%), and single-center (63%). Trial demographics have remained unchanged over time. Median trial sample size was 64 (interquartile range 29-192) with 10% of trials enrolling ≥500 participants. Most trials were completed within 5 years of enrollment start (69%). Trial characteristics varied considerably across National Institutes of Health Institutes and Centers. Results were reported under the assumptions that most National Institutes of Health-funded trials are registered in ClinicalTrials.gov and that trials are being registered completely and accurately. Conclusion In conclusion, there has been a decline in the number of trials being funded over time, explained in part by a relatively constant budget, increases in trial costs, or other factors that cannot be quantified. National Institutes of Health-funded trials are relatively small and tend to be single-centered. There are substantial differences in the number and types of trials done by Institutes and Centers within the National Institutes of Health.

Evidence-based value of subcutaneous surgical wound drainage: the largest systematic review and meta-analysis.

PubMed

Kosins, Aaron M; Scholz, Thomas; Cetinkaya, Mine; Evans, Gregory R D

2013-08-01

The purpose of this study was to determine the evidenced-based value of prophylactic drainage of subcutaneous wounds in surgery. An electronic search was performed. Articles comparing subcutaneous prophylactic drainage with no drainage were identified and classified by level of evidence. If sufficient randomized controlled trials were included, a meta-analysis was performed using the random-effects model. Fifty-two randomized controlled trials were included in the meta-analysis, and subgroups were determined by specific surgical procedures or characteristics (cesarean delivery, abdominal wound, breast reduction, breast biopsy, femoral wound, axillary lymph node dissection, hip and knee arthroplasty, obesity, and clean-contaminated wound). Studies were compared for the following endpoints: hematoma, wound healing issues, seroma, abscess, and infection. Fifty-two studies with a total of 6930 operations were identified as suitable for this analysis. There were 3495 operations in the drain group and 3435 in the no-drain group. Prophylactic subcutaneous drainage offered a statistically significant advantage only for (1) prevention of hematomas in breast biopsy procedures and (2) prevention of seromas in axillary node dissections. In all other procedures studied, drainage did not offer an advantage. Many surgical operations can be performed safely without prophylactic drainage. Surgeons can consider omitting drains after cesarean section, breast reduction, abdominal wounds, femoral wounds, and hip and knee joint replacement. Furthermore, surgeons should consider not placing drains prophylactically in obese patients. However, drain placement following a surgical procedure is the surgeon's choice and can be based on multiple factors beyond the type of procedure being performed or the patient's body habitus. Therapeutic, II.

Examination of Broad Symptom Improvement Resulting From Mindfulness-Based Stress Reduction in Breast Cancer Survivors: A Randomized Controlled Trial

PubMed Central

Reich, Richard R.; Paterson, Carly L.; Ramesar, Sophia; Park, Jong Y.; Alinat, Carissa; Johnson-Mallard, Versie; Moscoso, Manolete; Budhrani-Shani, Pinky; Miladinovic, Branko; Jacobsen, Paul B.; Cox, Charles E.; Goodman, Matthew; Kip, Kevin E.

2016-01-01

Purpose The purpose of this randomized trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR[BC]) program in improving psychological and physical symptoms and quality of life among breast cancer survivors (BCSs) who completed treatment. Outcomes were assessed immediately after 6 weeks of MBSR(BC) training and 6 weeks later to test efficacy over an extended timeframe. Patients and Methods A total of 322 BCSs were randomly assigned to either a 6-week MBSR(BC) program (n = 155) or a usual care group (n = 167). Psychological (depression, anxiety, stress, and fear of recurrence) and physical symptoms (fatigue and pain) and quality of life (as related to health) were assessed at baseline and at 6 and 12 weeks. Linear mixed models were used to assess MBSR(BC) effects over time, and participant characteristics at baseline were also tested as moderators of MBSR(BC) effects. Results Results demonstrated extended improvement for the MBSR(BC) group compared with usual care in both psychological symptoms of anxiety, fear of recurrence overall, and fear of recurrence problems and physical symptoms of fatigue severity and fatigue interference (P < .01). Overall effect sizes were largest for fear of recurrence problems (d = 0.35) and fatigue severity (d = 0.27). Moderation effects showed BCSs with the highest levels of stress at baseline experienced the greatest benefit from MBSR(BC). Conclusion The MBSR(BC) program significantly improved a broad range of symptoms among BCSs up to 6 weeks after MBSR(BC) training, with generally small to moderate overall effect sizes. PMID:27247219

Risk of Drug Resistance Among Persons Acquiring HIV Within a Randomized Clinical Trial of Single- or Dual-Agent Preexposure Prophylaxis

PubMed Central

Lehman, Dara A.; Baeten, Jared M.; McCoy, Connor O.; Weis, Julie F.; Peterson, Dylan; Mbara, Gerald; Donnell, Deborah; Thomas, Katherine K.; Hendrix, Craig W.; Marzinke, Mark A.; Frenkel, Lisa; Ndase, Patrick; Mugo, Nelly R.; Celum, Connie; Overbaugh, Julie; Matsen, Frederick A.; Celum, Connie; Baeten, Jared M.; Donnell, Deborah; Coombs, Robert W.; Frenkel, Lisa; Hendrix, Craig W.; Marzinke, Mark A.; Lingappa, Jairam; McElrath, M. Juliana; Fife, Kenneth; Were, Edwin; Tumwesigye, Elioda; Ndase, Patrick; Katabira, Elly; Katabira, Elly; Ronald, Allan; Bukusi, Elizabeth; Cohen, Craig; Wangisi, Jonathan; Campbell, James; Tappero, Jordan; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Mugo, Nelly Rwamba; Campbell, James; Tappero, Jordan; Wangisi, Jonathan

2015-01-01

Background. Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use. Methods. Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing. Results. Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment. Conclusions. These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF. PMID:25587020

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

PubMed

Azoulay, Elie; Lemiale, Virginie; Mokart, Djamel; Nseir, Saad; Argaud, Laurent; Pène, Frédéric; Kontar, Loay; Bruneel, Fabrice; Klouche, Kada; Barbier, François; Reignier, Jean; Stoclin, Anabelle; Louis, Guillaume; Constantin, Jean-Michel; Mayaux, Julien; Wallet, Florent; Kouatchet, Achille; Peigne, Vincent; Perez, Pierre; Girault, Christophe; Jaber, Samir; Oziel, Johanna; Nyunga, Martine; Terzi, Nicolas; Bouadma, Lila; Lebert, Christine; Lautrette, Alexandre; Bigé, Naike; Raphalen, Jean-Herlé; Papazian, Laurent; Rabbat, Antoine; Darmon, Michael; Chevret, Sylvie; Demoule, Alexandre

2018-03-05

Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO 2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO 2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

PubMed Central

Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.

PubMed

Chin, Melanie P; Bakris, George L; Block, Geoffrey A; Chertow, Glenn M; Goldsberry, Angie; Inker, Lesley A; Heerspink, Hiddo J L; O'Grady, Megan; Pergola, Pablo E; Wanner, Christoph; Warnock, David G; Meyer, Colin J

2018-01-01

Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001). Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. © 2018 The Author(s) Published by S. Karger AG, Basel.

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

PubMed

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

2016-02-01

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

Integrated mental health care and vocational rehabilitation to improve return to work rates for people on sick leave because of depression and anxiety (the Danish IBBIS trial): study protocol for a randomized controlled trial.

PubMed

Poulsen, Rie; Hoff, Andreas; Fisker, Jonas; Hjorthøj, Carsten; Eplov, Lene Falgaard

2017-12-02

Depression and anxiety are among the largest contributors to the global burden of disease and have negative effects on both the individual and society. Depression and anxiety are very likely to influence the individual's work ability, and up to 40% of the people on sick leave in Denmark have depression and/or anxiety. There is no clear evidence that treatment alone will provide sufficient support for vocational recovery in this group. Integrated vocational and health care services have shown good effects on return to work in other, similar welfare contexts. The purpose of the IBBIS (Integrated Mental Health Care and Vocational Rehabilitation to Individuals on Sick Leave Due to Anxiety and Depression) interventions is to improve and hasten the process of return to employment for people in Denmark on sick leave because of depression and anxiety. This three-arm, parallel-group, randomized superiority trial has been set up to investigate the effectiveness of the IBBIS mental health care intervention and the integrated IBBIS mental health care and IBBIS vocational rehabilitation intervention for people on sick leave because of depression and/or anxiety in Denmark. The trial has an investigator-initiated multicenter design. A total of 603 patients will be recruited from Danish job centers in 4 municipalities and randomly assigned to one of 3 groups: (1) IBBIS mental health care integrated with IBBIS vocational rehabilitation, (2) IBBIS mental health care and standard vocational rehabilitation, and (3) standard mental health care and standard vocational rehabilitation. The primary outcome is register-based return to work at 12 months. The secondary outcome measures are self-assessed level of depression (Beck Depression Inventory II), anxiety (Beck Anxiety Inventory), stress symptoms (Four-Dimensional Symptom Questionnaire), work and social functioning (Work and Social Adjustment Scale), and register-based recurrent sickness absence. This study will provide new knowledge on vocational recovery, integrated vocational and health care interventions, and prevention of recurrent sickness absence among people with depression and anxiety. If the effect on return to work is different in the intervention groups, this study can contribute to current knowledge on shared care models for health care and vocational rehabilitation services. ClinicalTrials.gov, NCT02872051 . Retrospectively registered on 15 August 2016.

Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study.

PubMed

Paramasivan, S; Rogers, C A; Welbourn, R; Byrne, J P; Salter, N; Mahon, D; Noble, H; Kelly, J; Mazza, G; Whybrow, P; Andrews, R C; Wilson, C; Blazeby, J M; Donovan, J L

2017-11-01

Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI). The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization. Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers. The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.

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),…

Value for money: economic evaluation of two different caries prevention programmes compared with standard care in a randomized controlled trial.

PubMed

Vermaire, J H; van Loveren, C; Brouwer, W B F; Krol, M

2014-01-01

A cost-effectiveness analysis was conducted during a 3-year randomized controlled clinical trial in a general dental practice in the Netherlands in which 230 6-year-old children (± 3 months) were assigned to either regular dental care, an increased professional fluoride application (IPFA) programme or a non-operative caries treatment and prevention (NOCTP) programme. Information on resource use during the 3-year period was documented by the dental nurse at every patient visit, such as treatment time, travel time and travel distance. Caries increment scores (at D3MFS level) were used to assess effectiveness. Cost calculations were performed using bottom-up micro-costing. Incremental cost-effectiveness ratios (ICERs) were expressed as additional average costs per prevented DMFS. The ICERs compared with regular dental care from a health care system perspective and societal perspective were, respectively, EUR 269 and EUR 1,369 per prevented DMFS in the IPFA programme, and EUR 30 and EUR 100 in the NOCTP programme. The largest investments for the NOCTP group were made in the first year of the study; they decreased in the second and equalled the costs of control group in third year of the study. From both medical and economic points of view, the NOCTP strategy may be considered the preferred strategy for caries prevention.

Management of oral lesions in HIV-positive patients.

PubMed

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

2007-03-01

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

Protocol for the "Michigan Awareness Control Study": A prospective, randomized, controlled trial comparing electronic alerts based on bispectral index monitoring or minimum alveolar concentration for the prevention of intraoperative awareness.

PubMed

Mashour, George A; Tremper, Kevin K; Avidan, Michael S

2009-11-05

The incidence of intraoperative awareness with explicit recall is 1-2/1000 cases in the United States. The Bispectral Index monitor is an electroencephalographic method of assessing anesthetic depth that has been shown in one prospective study to reduce the incidence of awareness in the high-risk population. In the B-Aware trial, the number needed to treat in order to prevent one case of awareness in the high-risk population was 138. Since the number needed to treat and the associated cost of treatment would be much higher in the general population, the efficacy of the Bispectral Index monitor in preventing awareness in all anesthetized patients needs to be clearly established. This is especially true given the findings of the B-Unaware trial, which demonstrated no significant difference between protocols based on the Bispectral Index monitor or minimum alveolar concentration for the reduction of awareness in high risk patients. To evaluate efficacy in the general population, we are conducting a prospective, randomized, controlled trial comparing the Bispectral Index monitor to a non-electroencephalographic gauge of anesthetic depth. The total recruitment for the study is targeted for 30,000 patients at both low and high risk for awareness. We have developed a novel algorithm that is capable of real-time analysis of our electronic perioperative information system. In one arm of the study, anesthesia providers will receive an electronic page if the Bispectral Index value is >60. In the other arm of the study, anesthesia providers will receive a page if the age-adjusted minimum alveolar concentration is <0.5. Our minimum alveolar concentration algorithm is sensitive to both inhalational anesthetics and intravenous sedative-hypnotic agents. Awareness during general anesthesia is a persistent problem and the role of the Bispectral Index monitor in its prevention is still unclear. The Michigan Awareness Control Study is the largest prospective trial of awareness prevention ever conducted. Clinical Trial NCT00689091.

Effect of an Internet-based, personalized nutrition randomized trial on dietary changes associated with the Mediterranean diet: the Food4Me Study.

PubMed

Livingstone, Katherine M; Celis-Morales, Carlos; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Macready, Anna L; Fallaize, Rosalind; Forster, Hannah; Woolhead, Clara; O'Donovan, Clare B; Marsaux, Cyril Fm; Kolossa, Silvia; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Drevon, Christian A; Manios, Yannis; Traczyk, Iwona; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Saris, Wim H; Daniel, Hannelore; Gibney, Mike; Martinez, J Alfredo; Mathers, John C

2016-08-01

Little is known about the efficacy of personalized nutrition (PN) interventions for improving consumption of a Mediterranean diet (MedDiet). The objective was to evaluate the effect of a PN intervention on dietary changes associated with the MedDiet. Participants (n = 1607) were recruited into a 6-mo, Internet-based, PN randomized controlled trial (Food4Me) designed to evaluate the effect of PN on dietary change. Participants were randomly assigned to receive conventional dietary advice [control; level 0 (L0)] or PN advice on the basis of current diet [level 1 (L1)], diet and phenotype [level 2 (L2)], or diet, phenotype, and genotype [level 3 (L3)]. Dietary intakes from food-frequency questionnaires at baseline and at 6 mo were converted to a MedDiet score. Linear regression compared participant characteristics between high (>5) and low (≤5) MedDiet scores. Differences in MedDiet scores between treatment arms at month 6 were evaluated by using contrast analyses. At baseline, high MedDiet scorers had a 0.5 lower body mass index (in kg/m(2); P = 0.007) and a 0.03 higher physical activity level (P = 0.003) than did low scorers. MedDiet scores at month 6 were greater in individuals randomly assigned to receive PN (L1, L2, and L3) than in controls (PN compared with controls: 5.20 ± 0.05 and 5.48 ± 0.07, respectively; P = 0.002). There was no significant difference in MedDiet scores at month 6 between PN advice on the basis of L1 compared with L2 and L3. However, differences in MedDiet scores at month 6 were greater in L3 than in L2 (L3 compared with L2: 5.63 ± 0.10 and 5.38 ± 0.10, respectively; P = 0.029). Higher MedDiet scores at baseline were associated with healthier lifestyles and lower adiposity. After the intervention, MedDiet scores were greater in individuals randomly assigned to receive PN than in controls, with the addition of DNA-based dietary advice resulting in the largest differences in MedDiet scores. Although differences were significant, their clinical relevance is modest. This trial was registered at clinicaltrials.gov as NCT01530139. © 2016 American Society for Nutrition.

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.

Comparison of the efficacy of three PubMed search filters in finding randomized controlled trials to answer clinical questions.

PubMed

Yousefi-Nooraie, Reza; Irani, Shirin; Mortaz-Hedjri, Soroush; Shakiba, Behnam

2013-10-01

The aim of this study was to compare the performance of three search methods in the retrieval of relevant clinical trials from PubMed to answer specific clinical questions. Included studies of a sample of 100 Cochrane reviews which recorded in PubMed were considered as the reference standard. The search queries were formulated based on the systematic review titles. Precision, recall and number of retrieved records for limiting the results to clinical trial publication type, and using sensitive and specific clinical queries filters were compared. The number of keywords, presence of specific names of intervention and syndrome in the search keywords were used in a model to predict the recalls and precisions. The Clinical queries-sensitive search strategy retrieved the largest number of records (33) and had the highest recall (41.6%) and lowest precision (4.8%). The presence of specific intervention name was the only significant predictor of all recalls and precisions (P = 0.016). The recall and precision of combination of simple clinical search queries and methodological search filters to find clinical trials in various subjects were considerably low. The limit field strategy yielded in higher precision and fewer retrieved records and approximately similar recall, compared with the clinical queries-sensitive strategy. Presence of specific intervention name in the search keywords increased both recall and precision. © 2010 John Wiley & Sons Ltd.

Types of intraocular lenses for cataract surgery in eyes with uveitis

PubMed Central

Leung, Theresa G; Lindsley, Kristina; Kuo, Irene C

2014-01-01

Background Cataract formation often occurs in people with uveitis. It is unclear which intraocular lens (IOL) type is optimal for use in cataract surgery for eyes with uveitis. Objectives To summarize the effects of different IOLs on visual acuity, other visual outcomes, and quality of life in people with uveitis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 August 2013. We also performed forward and backward searching using the Science Citation Index and the reference lists of the included studies, respectively, in August 2013. Selection criteria We included randomized controlled trials (RCTs) comparing hydrophobic or hydrophilic acrylic, silicone, or poly(methyl methacrylate) (PMMA) IOLs with or without heparin-surface modification (HSM), with each other, or with no treatment in adults with uveitis, for any indication, undergoing cataract surgery. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors screened the search results and for included studies, assessed the risk of bias and extracted data independently. We contacted study investigators for additional information. We did not perform a meta-analysis due to variability in reporting and follow-up intervals for the primary and secondary outcomes of interest. Main results We included four RCTs involving 216 participants (range of 2 to 140 participants with uveitic cataract per trial) and comparing up to four types of IOLs. The largest study was an international study with centers in Brazil, Egypt, Finland, France, Japan, the Netherlands, Slovak Republic, Spain, and the USA; two studies were conducted in Germany and one in Saudi Arabia. There was substantial heterogeneity with respect to the ages of participants and etiologies of uveitis within and across studies. The length of follow-up among the studies ranged from 1 to 24 months after cataract surgery. The studies were at low risk of selection bias, but two of the four studies did not employ masking and only one study included all randomized participants in the final analyses. The funding source was disclosed by investigators of the largest study (professional society) and not reported by the other three. Due to heterogeneity in lens types evaluated and outcomes reported among the trials, we did not combine data in a meta-analysis. In the largest study (140 participants), the study eye of each participant was randomized to receive one of four types of IOLs: hydrophobic acrylic, silicone, HSM PMMA, or unmodified PMMA. Proportions of participants with one or more Snellen lines of visual improvement were similar among the four treatment groups at one year' follow-up: 45 of 48 (94%) in the hydrophobic acrylic IOL group, 39 of 44 (89%) in the silicone IOL group, 18 of 22 (82%) in the HSM PMMA IOL group, and 22 of 26 (85%) in the unmodified PMMA IOL group. When comparing hydrophobic acrylic IOLs with silicone IOLs, the risk ratio (RR) was 1.06 (95% confidence interval (CI) 0.93 to 1.20). At one year' follow-up, fewer eyes randomized to hydrophobic acrylic IOLs developed posterior synechiae when compared with eyes receiving silicone IOLs (RR 0.18, 95% CI 0.04 to 0.79); the effects between these groups were less certain with respect to developing posterior capsule opacification (PCO) (RR 0.74, 95% CI 0.41 to 1.37), corneal edema (RR 0.49, 95% CI 0.22 to 1.12), cystoid macular edema (RR 0.10, 95% CI 0.01 to 1.84), or mild IOL decentration (RR 0.92, 95% CI 0.06 to 14.22). Two intra-individual studies also compared HSM PMMA IOLs with unmodified PMMA IOLs at three or six months of follow-up. These studies, including a combined total of 16 participants with uveitis, were insufficiently powered to detect differences in outcomes among eyes of people with uveitis randomized to receive HSM PMMA IOLs when compared with fellow eyes receiving unmodified PMMA IOLs. In the fourth study (60 participants), the study eye of each participant was randomized to receive a hydrophobic or hydrophilic acrylic IOL. At three months, there were no statistical or clinical differences between hydrophobic and hydrophilic acrylic IOL types in the proportions of participants with two or more Snellen lines of visual improvement (RR 1.03, 95% CI 0.87 to 1.22). There were similar rates in the development of PCO between hydrophobic or hydrophilic acrylic IOLs at six months' follow-up (RR 1.00, 95% CI 0.80 to 1.25). The effect of the lenses on posterior synechiae was uncertain at six months' follow-up (RR 0.50, 95% CI 0.05 to 5.22). None of the included studies reported quality of life outcomes. Authors' conclusions Based on the trials identified in this review, there is uncertainty as to which type of IOL provides the best visual and clinical outcomes in people with uveitis undergoing cataract surgery. The studies were small, not all lens materials were compared in all studies, and not all lens materials were available in all study sites. Evidence of a superior effect of hydrophobic acrylic lenses over silicone lenses, specifically for posterior synechiae outcomes comes from a single study at a high risk of performance and detection bias. However, due to small sample sizes and heterogeneity in outcome reporting, we found insufficient information to assess these and other types of IOL materials for cataract surgery for eyes with uveitis. PMID:24590672

Renal denervation: What happened, and why?

PubMed

Shishehbor, Mehdi H; Hammad, Tarek A; Thomas, George

2017-09-01

Despite promising results in initial trials, renal denervation failed to achieve its efficacy end points as a treatment for resistant hypertension in the SYMPLICITY HTN-3 trial, the largest trial of this treatment to date (N Engl J Med 2014; 370:1393-1401). Is renal denervation dead, or will future trials and newer technology revive it? Copyright © 2017 Cleveland Clinic.

Bayesian adaptive trials offer advantages in comparative effectiveness trials: an example in status epilepticus.

PubMed

Connor, Jason T; Elm, Jordan J; Broglio, Kristine R

2013-08-01

We present a novel Bayesian adaptive comparative effectiveness trial comparing three treatments for status epilepticus that uses adaptive randomization with potential early stopping. The trial will enroll 720 unique patients in emergency departments and uses a Bayesian adaptive design. The trial design is compared to a trial without adaptive randomization and produces an efficient trial in which a higher proportion of patients are likely to be randomized to the most effective treatment arm while generally using fewer total patients and offers higher power than an analogous trial with fixed randomization when identifying a superior treatment. When one treatment is superior to the other two, the trial design provides better patient care, higher power, and a lower expected sample size. Copyright © 2013 Elsevier Inc. All rights reserved.

Are probiotics effective in preventing urinary tract infection?

PubMed

Canales, Juan; Rada, Gabriel

2018-04-04

Urinary tract infection is the most common bacterial infection and recurrences are common. Probiotics have been proposed as an alternative to decrease this risk. However, it is not clear if they are really effective. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We identified six systematic reviews including nine studies overall, of which seven were randomized trials. We concluded it is not clear whether probiotics decrease the risk of symptomatic urinary tract infection, because the certainty of the evidence is very low.

What is the effectiveness of systemic corticosteroids in children with croup?

PubMed

Muñoz-Osores, Elizabeth; Arenas, Deidyland

2017-06-06

Systemic corticosteroids constitute standard treatment in children with acute obstructive laryngitis (croup). However, there is some uncertainty in relation with the magnitude of the benefits and risks associated with their use. To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We identified six systematic reviews including 25 randomized trials relevant for the question of interest. We extracted data from the systematic reviews, reananalysed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded the use of systemic corticosteroids increases the number of patients with clinical improvement at 12 hours and reduces the risk of readmission.

A New Model of Reverse Cholesterol Transport: EnTICEing Strategies to Stimulate Intestinal Cholesterol Excretion

PubMed Central

Temel, Ryan E.; Brown, J. Mark

2015-01-01

Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention. PMID:25930707

Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

PubMed

Holodniy, Mark; Brown, Sheldon T; Cameron, D William; Kyriakides, Tassos C; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

2011-03-31

Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Clinicaltrials.gov NCT00050089.

Use of Theory in Behavior Change Interventions: An Analysis of Programs to Increase Physical Activity in Posttreatment Breast Cancer Survivors

PubMed Central

Bluethmann, Shirley M.; Bartholomew, L. Kay; Murphy, Caitlin C.; Vernon, Sally W.

2017-01-01

Objective Theory use may enhance effectiveness of behavioral interventions, yet critics question whether theory-based interventions have been sufficiently scrutinized. This study applied a framework to evaluate theory use in physical activity interventions for breast cancer survivors. The aims were to (1) evaluate theory application intensity and (2) assess the association between extensiveness of theory use and intervention effectiveness. Methods Studies were previously identified through a systematic search, including only randomized controlled trials published from 2005 to 2013, that addressed physical activity behavior change and studied survivors who were <5 years posttreatment. Eight theory items from Michie and Prestwich’s coding framework were selected to calculate theory intensity scores. Studies were classified into three subgroups based on extensiveness of theory use (Level 1 = sparse; Level 2 = moderate; and Level 3 = extensive). Results Fourteen randomized controlled trials met search criteria. Most trials used the transtheoretical model (n = 5) or social cognitive theory (n = 3). For extensiveness of theory use, 5 studies were classified as Level 1, 4 as Level 2, and 5 as Level 3. Studies in the extensive group (Level 3) had the largest overall effect size (g = 0.76). Effects were more modest in Level 1 and 2 groups with overall effect sizes of g = 0.28 and g = 0.36, respectively. Conclusions Theory use is often viewed as essential to behavior change, but theory application varies widely. In this study, there was some evidence to suggest that extensiveness of theory use enhanced intervention effectiveness. However, there is more to learn about how theory can improve interventions for breast cancer survivors. PMID:27226430

Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials.

PubMed

Li, Jie-Li; Fan, Guang-Yu; Liu, Yu-Jie; Zeng, Zi-Hang; Huang, Jing-Juan; Yang, Zong-Ming; Meng, Xiang-Yu

2018-01-01

We aimed to quantitatively synthesize data from randomized controlled trials (RCTs) concerning maintenance for multiple myeloma (MM). We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA) to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA) to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS) but not overall survival (OS). Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR) = 0.59, 95% Confidence Interval (CI) = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len)-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001). NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial

PubMed Central

Tabouret, Emeline; Houillier, Caroline; Martin-Duverneuil, Nadine; Blonski, Marie; Soussain, Carole; Ghesquières, Herve; Houot, Roch; Larrieu, Delphine; Soubeyran, Pierre; Gressin, Remy; Gyan, Emmanuel; Chinot, Olivier; Taillandier, Luc; Choquet, Sylvain; Alentorn, Agusti; Leclercq, Delphine; Omuro, Antonio; Tanguy, Marie-Laure

2017-01-01

Abstract Background. Our aim was to review MRI characteristics of patients with primary CNS lymphoma (PCNSL) enrolled in a randomized phase II trial and to evaluate their potential prognostic value and patterns of relapse, including T2 fluid attenuated inversion recovery (FLAIR) MRI abnormalities. Methods. Neuroimaging findings in 85 patients with PCNSL enrolled in a prospective trial were reviewed blinded to outcomes. MRI characteristics and responses according to International PCNSL Collaborative Group (IPCG) criteria were correlated with progression-free survival (PFS) and overall survival (OS). Results. Multivariate analysis showed that objective response at 2 months (P < .001) and at end of treatment (P = .015) were predictors of prolonged OS. Infratentorial location (P = .008) and large (>11.4 cm3) enhancing tumor volume (P = .006) were associated with poor OS and PFS, respectively. Ratio of change in product of largest diameters at early MRI evaluation but not timing of complete response achievement (early vs delayed) was prognostic for OS. Sixty-nine patients relapsed. Relapse in the brain (n = 52) involved an initial enhancing site, a different site, or both in 46%, 40%, and 14% of patients, respectively. At baseline, non-enhancing T2-FLAIR hypersignal lesions distant from the enhancing tumor site were detected in 18 patients. These lesions markedly decreased (>50%) in 16 patients after chemotherapy, supporting their neoplastic nature. Of these patients, 10/18 relapsed, half (n = 5) in the initially non-enhancing T2-FLAIR lesions. Conclusions. Baseline tumor size and infratentorial localization are of prognostic value in PCNSL. Our findings provide evidence that non-enhancing FLAIR abnormalities may add to overall tumor burden, suggesting that response criteria should be refined to incorporate evaluation of T2-weighted/FLAIR sequences. PMID:27994065

Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial.

PubMed

Kirton, Adam; Andersen, John; Herrero, Mia; Nettel-Aguirre, Alberto; Carsolio, Lisa; Damji, Omar; Keess, Jamie; Mineyko, Aleksandra; Hodge, Jacquie; Hill, Michael D

2016-05-03

To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis. A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6-19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model). All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57-8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand. Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement. This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy. © 2016 American Academy of Neurology.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

PubMed

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-05-01

Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. © 2014 The British Pharmacological Society.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis

PubMed Central

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-01-01

Aims Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. Methods We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. Results From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l−1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l−1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Conclusions Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. PMID:25377481

Age effects on discrimination of timing in auditory sequences

NASA Astrophysics Data System (ADS)

Fitzgibbons, Peter J.; Gordon-Salant, Sandra

2004-08-01

The experiments examined age-related changes in temporal sensitivity to increments in the interonset intervals (IOI) of components in tonal sequences. Discrimination was examined using reference sequences consisting of five 50-ms tones separated by silent intervals; tone frequencies were either fixed at 4 kHz or varied within a 2-4-kHz range to produce spectrally complex patterns. The tonal IOIs within the reference sequences were either equal (200 or 600 ms) or varied individually with an average value of 200 or 600 ms to produce temporally complex patterns. The difference limen (DL) for increments of IOI was measured. Comparison sequences featured either equal increments in all tonal IOIs or increments in a single target IOI, with the sequential location of the target changing randomly across trials. Four groups of younger and older adults with and without sensorineural hearing loss participated. Results indicated that DLs for uniform changes of sequence rate were smaller than DLs for single target intervals, with the largest DLs observed for single targets embedded within temporally complex sequences. Older listeners performed more poorly than younger listeners in all conditions, but the largest age-related differences were observed for temporally complex stimulus conditions. No systematic effects of hearing loss were observed.

Exercise Training for Blood Pressure: A Systematic Review and Meta‐analysis

PubMed Central

Cornelissen, Veronique A.; Smart, Neil A.

2013-01-01

Background We conducted meta‐analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes. Methods and Results Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer‐reviewed journal up to February 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (SBP) was reduced after endurance (−3.5 mm Hg [confidence limits −4.6 to −2.3]), dynamic resistance (−1.8 mm Hg [−3.7 to −0.011]), and isometric resistance (−10.9 mm Hg [−14.5 to −7.4]) but not after combined training. Reductions in diastolic BP (DBP) were observed after endurance (−2.5 mm Hg [−3.2 to −1.7]), dynamic resistance (−3.2 mm Hg [−4.5 to −2.0]), isometric resistance (−6.2 mm Hg [−10.3 to −2.0]), and combined (−2.2 mm Hg [−3.9 to −0.48]) training. BP reductions after endurance training were greater (P<0.0001) in 26 study groups of hypertensive subjects (−8.3 [−10.7 to −6.0]/−5.2 [−6.8 to −3.4] mm Hg) than in 50 groups of prehypertensive subjects (−2.1 [−3.3 to −0.83]/−1.7 [−2.7 to −0.68]) and 29 groups of subjects with normal BP levels (−0.75 [−2.2 to +0.69]/−1.1 [−2.2 to −0.068]). BP reductions after dynamic resistance training were largest for prehypertensive participants (−4.0 [−7.4 to −0.5]/−3.8 [−5.7 to −1.9] mm Hg) compared with patients with hypertension or normal BP. Conclusion Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in SBP. PMID:23525435

Cockpit Window Edge Proximity Effects on Judgements of Horizon Vertical Displacement

NASA Technical Reports Server (NTRS)

Haines, R. F.

1984-01-01

To quantify the influence of a spatially fixed edge on vertical displacement threshold, twenty-four males (12 pilots, 12 non-pilots) were presented a series of forced choice, paired comparison trials in which a 32 deg arc wide, thin, luminous horizontal stimulus line moved smoothly downward through five angles from a common starting position within a three second-long period. The five angles were 1.4, 1.7, 2, 2.3, and 2.6 deg. Each angle was presented paired with itself and the other four angles in all combinations in random order. For each pair of trials the observer had to choose which trial possessed the largest displacement. A confidence response also was made. The independent variable was the angular separation between the lower edge of a stable 'window' aperture through which the stimulus was seen to move and the lowest position attained by the stimulus. It was found that vertical displacement accuracy is inversely related to the angle separating the stimulus and the fixed window edge (p = .05). In addition, there is a strong tendency for pilot confidence to be lower than that of non-pilots for each of the three angular separations. These results are discussed in erms of selected cockpit features and as they relate to how pilots judge changes in aircraft pitch attitude.

Genetic progress in homogeneous regions of wheat cultivation in Rio Grande do Sul State, Brazil.

PubMed

Follmann, D N; Cargnelutti Filho, A; Lúcio, A D; de Souza, V Q; Caraffa, M; Wartha, C A

2017-03-30

The State of Rio Grande do Sul (RS) stands out as the largest wheat producer in Brazil. Wheat is the most emphasized winter cereal in RS, attracting public and private investments directed to wheat genetic breeding. The study of genetic progress should be performed routinely at breeding programs to study the behavior of cultivars developed for homogeneous regions of cultivation. The objectives of this study were: 1) to evaluate the genetic progress of wheat grain yield in RS; 2) to evaluate the influence of cultivar competition trial stratification in homogeneous regions of cultivation on the study of genetic progress. Grain yield data of 122 wheat cultivars evaluated in 137 trials arranged in randomized block design with three or four replications were used. Field trials were carried out in 23 locations in RS divided into two homogeneous regions during the period from 2002 to 2013. Genetic progress for RS and homogeneous regions was studied utilizing the method proposed by Vencovsky. Annual genetic progress for wheat grain yield during the period of 12 years in the State of RS was 2.86%, oscillating between homogeneous regions of cultivation. The difference of annual genetic progress in region 1 (1.82%) in relation to region 2 (4.38%) justifies the study of genetic progress by homogeneous regions of cultivation.

Treatment Trials for Neonatal Seizures: The Effect of Design on Sample Size

PubMed Central

Stevenson, Nathan J.; Boylan, Geraldine B.; Hellström-Westas, Lena; Vanhatalo, Sampsa

2016-01-01

Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations. We used five outcome measures, three AED protocols, eight treatment delays from seizure onset (Td) and four levels of trial AED efficacy to simulate different RCTs. We performed power calculations for each RCT design and analysed the resultant sample size. We also assessed the rate of false positives, or placebo effect, in typical uncontrolled studies. We found that the false positive rate ranged from 5 to 85% of patients depending on RCT design. For controlled trials, the choice of outcome measure had the largest effect on sample size with median differences of 30.7 fold (IQR: 13.7–40.0) across a range of AED protocols, Td and trial AED efficacy (p<0.001). RCTs that compared the trial AED with positive controls required sample sizes with a median fold increase of 3.2 (IQR: 1.9–11.9; p<0.001). Delays in AED administration from seizure onset also increased the required sample size 2.1 fold (IQR: 1.7–2.9; p<0.001). Subgroup analysis showed that RCTs in neonates treated with hypothermia required a median fold increase in sample size of 2.6 (IQR: 2.4–3.0) compared to trials in normothermic neonates (p<0.001). These results show that RCT design has a profound influence on the required sample size. Trials that use a control group, appropriate outcome measure, and control for differences in Td between groups in analysis will be valid and minimise sample size. PMID:27824913

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

A randomized controlled trial of mindfulness meditation for chronic insomnia.

PubMed

Ong, Jason C; Manber, Rachel; Segal, Zindel; Xia, Yinglin; Shapiro, Shauna; Wyatt, James K

2014-09-01

To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. Three-arm, single-site, randomized controlled trial. Academic medical center. Fifty-four adults with chronic insomnia. Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781. © 2014 Associated Professional Sleep Societies, LLC.

Rationale, design, and baseline findings from Seamos Saludables: a randomized controlled trial testing the efficacy of a culturally and linguistically adapted, computer- tailored physical activity intervention for Latinas

PubMed Central

Pekmezi, Dori; Dunsiger, Shira; Gans, Kim; Bock, Beth; Gaskins, Ronnesia; Marquez, Becky; Lee, Christina; Neighbors, Charles; Jennings, Ernestine; Tilkemeier, Peter; Marcus, Bess

2012-01-01

Background Latinos are now the largest (and fastest growing) ethnic minority group in the United States. Latinas report high rates of physical inactivity and suffer disproportionately from obesity, diabetes, and other conditions that are associated with sedentary lifestyles. Effective physical activity interventions are urgently needed to address these health disparities. Method/Design An ongoing randomized controlled trial will test the efficacy of a home-based, individually tailored physical activity print intervention for Latinas (1R01NR011295). This program was culturally and linguistically adapted for the target population through extensive formative research (6 focus groups, 25 cognitive interviews, iterative translation process). This participant feedback was used to inform intervention development. Then, 268 sedentary Latinas were randomly assigned to receive either the Tailored Intervention or the Wellness Contact Control arm. The intervention, based on Social Cognitive Theory and the Transtheoretical Model, consists of six months of regular mailings of motivation-matched physical activity manuals and tip sheets and individually tailored feedback reports generated by a computer expert system, followed by a tapered dose of mailings during the second six months (maintenance phase). The main outcome is change in minutes/week of physical activity at six months and one year as measured by the 7-Day Physical Activity Recall (7-Day PAR). To validate these findings, accelerometer data will be collected at the same time points. Discussion High reach, low cost, culturally relevant interventions to encourage physical activity among Latinas could help reduce health disparities and thus have a substantial positive impact on public health. PMID:22789455

OpT2mise: a randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes-research design and methods.

PubMed

Aronson, Ronnie; Cohen, Ohad; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; de Portu, Simona; Lee, Scott; Reznik, Yves

2014-07-01

In insulin-requiring type 2 diabetes patients, current insulin therapy approaches such as basal-alone or basal-bolus multiple daily injections (MDI) have not consistently provided achievement of optimal glycemic control. Previous studies have suggested a potential benefit of continuous subcutaneous insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter, randomized, trial comparing CSII with MDI in a large cohort of subjects with evidence of persistent hyperglycemia despite previous MDI therapy. Subjects were enrolled into a run-in period for optimization of their MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated hemoglobin [HbA1c] ≥8% and ≤12%) were then randomly assigned to CSII or continuing an MDI regimen for a 6-month phase followed by a single crossover of the MDI arm, switching to CSII. The primary end point is the between-group difference in mean change in HbA1c from baseline to 6 months. Secondary end points include change in mean 24-h glucose values, area under the curve and time spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety end points include hypoglycemia, hospital admissions, and emergency room visits. When subject enrollment was completed in May 2013, 495 subjects had been enrolled in the study. The study completion for the primary end point is expected in January 2014. OpT2mise will represent the largest studied homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia despite optimized MDI therapy. OpT2mise will help define the role of CSII in insulin intensification and define its safety, rate of hypoglycemia, patient adherence, and patient satisfaction.

A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women.

PubMed

Manousou, S; Stål, M; Larsson, C; Mellberg, C; Lindahl, B; Eggertsen, R; Hulthén, L; Olsson, T; Ryberg, M; Sandberg, S; Nyström, H F

2018-01-01

Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet. A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium. At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group. A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.

Effect of Structured Touch and Guided Imagery for Pain and Anxiety in Elective Joint Replacement Patients--A Randomized Controlled Trial: M-TIJRP.

PubMed

Forward, John Brent; Greuter, Nancy Elizabeth; Crisall, Santa J; Lester, Houston F

2015-01-01

Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics. Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively. To investigate the effectiveness of the "M" Technique (M), a registered method of structured touch using a set sequence and number of strokes, and a consistent level of pressure on hands and feet, compared with guided imagery and usual care, for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery. Randomized controlled trial: M-TIJRP (MiTechnique and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a community hospital, 225 male and female patients, aged 38 to 90 years, undergoing elective total hip or knee replacement were randomly assigned to 1 of 3 groups (75 patients in each): M, guided imagery, or usual care. They were blinded to their assignment until the intervention. Reduction of pain and anxiety postoperatively. Secondary outcomes measured use of pain medication and patient satisfaction. This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care. M showed the largest predicted decreases in both pain and anxiety between groups. There was no significant difference in narcotic pain medication use between groups. Patient satisfaction survey ratings were highest for M, followed by guided imagery. The benefit of M may be because of the specifically structured sequence of touch by competent caring, trained providers.

Effect of Structured Touch and Guided Imagery for Pain and Anxiety in Elective Joint Replacement Patients—A Randomized Controlled Trial: M-TIJRP

PubMed Central

Forward, John Brent; Greuter, Nancy Elizabeth; Crisall, Santa J; Lester, Houston F

2015-01-01

Context: Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics. Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively. Objective: To investigate the effectiveness of the “M” Technique (M), a registered method of structured touch using a set sequence and number of strokes, and a consistent level of pressure on hands and feet, compared with guided imagery and usual care, for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery. Methods: Randomized controlled trial: M-TIJRP (MiTechnique and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a community hospital, 225 male and female patients, aged 38 to 90 years, undergoing elective total hip or knee replacement were randomly assigned to 1 of 3 groups (75 patients in each): M, guided imagery, or usual care. They were blinded to their assignment until the intervention. Main Outcome Measures: Reduction of pain and anxiety postoperatively. Secondary outcomes measured use of pain medication and patient satisfaction. Results: This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care. M showed the largest predicted decreases in both pain and anxiety between groups. There was no significant difference in narcotic pain medication use between groups. Patient satisfaction survey ratings were highest for M, followed by guided imagery. Conclusion: The benefit of M may be because of the specifically structured sequence of touch by competent caring, trained providers. PMID:26222093

Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy.

PubMed

Adams, David; Suhr, Ole B; Dyck, Peter J; Litchy, William J; Leahy, Raina G; Chen, Jihong; Gollob, Jared; Coelho, Teresa

2017-09-11

Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality. Here we describe the rationale and design of the Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled, global study to evaluate the efficacy and safety of patisiran in patients with hATTR amyloidosis with polyneuropathy. Eligible patients are 18-85 years old with hATTR amyloidosis, investigator-estimated survival of ≥2 years, Neuropathy Impairment Score (NIS) of 5-130, and polyneuropathy disability score ≤IIIb. Patients are randomized 2:1 to receive either intravenous patisiran 0.3 mg/kg or placebo once every 3 weeks. The primary objective is to determine the efficacy of patisiran at 18 months based on the difference in the change in modified NIS+7 (a composite measure of motor strength, sensation, reflexes, nerve conduction, and autonomic function) between the patisiran and placebo groups. Secondary objectives are to evaluate the effect of patisiran on Norfolk-Diabetic Neuropathy quality of life questionnaire score, nutritional status (as evaluated by modified body mass index), motor function (as measured by NIS-weakness and timed 10-m walk test), and autonomic symptoms (as measured by the Composite Autonomic Symptom Score-31 questionnaire). Exploratory objectives include assessment of cardiac function and pathologic evaluation to assess nerve fiber innervation and amyloid burden. Safety of patisiran will be assessed throughout the study. APOLLO represents the largest randomized, Phase 3 study to date in patients with hATTR amyloidosis, with endpoints that capture the multisystemic nature of this disease. This trial is registered at clinicaltrials.gov ( NCT01960348 ); October 9, 2013.

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 populations unless they are confident of the similarity between the trial sample and that target population. PMID:25307417

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 they are confident of the similarity between the trial sample and that target population.

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 ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs. Similar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.

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.

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 orthopaedic randomized clinical trials and their analysis.

Metacognitive monitoring during category learning: how success affects future behaviour.

PubMed

Doyle, Mario E; Hourihan, Kathleen L

2016-10-01

The purpose of this study was to see how people perceive their own learning during a category learning task, and whether their perceptions matched their performance. In two experiments, participants were asked to learn natural categories, of both high and low variability, and make category learning judgements (CLJs). Variability was manipulated by varying the number of exemplars and the number of times each exemplar was presented within each category. Experiment 1 showed that participants were generally overconfident in their knowledge of low variability families, suggesting that they considered repetition to be more useful for learning than it actually was. Also, a correct trial, for a particular category, was more likely to occur if the previous trial was correct. CLJs had the largest increase when a trial was correct following an incorrect trial and the largest decrease when an incorrect trial followed a correct trial. Experiment 2 replicated these results, but also demonstrated that global CLJ ratings showed the same bias towards repetition. These results indicate that we generally identify success as being the biggest determinant of learning, but do not always recognise cues, such as variability, that enhance learning.

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. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

PubMed

Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all

PubMed Central

Antonoglou, Georgios N.; Sándor, George K.; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date. PMID:28777820

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Computer-based psychological treatment for comorbid depression and problematic alcohol and/or cannabis use: a randomized controlled trial of clinical efficacy.

PubMed

Kay-Lambkin, Frances J; Baker, Amanda L; Lewin, Terry J; Carr, Vaughan J

2009-03-01

To evaluate computer- versus therapist-delivered psychological treatment for people with comorbid depression and alcohol/cannabis use problems. Randomized controlled trial. Community-based participants in the Hunter Region of New South Wales, Australia. Ninety-seven people with comorbid major depression and alcohol/cannabis misuse. All participants received a brief intervention (BI) for depressive symptoms and substance misuse, followed by random assignment to: no further treatment (BI alone); or nine sessions of motivational interviewing and cognitive behaviour therapy (intensive MI/CBT). Participants allocated to the intensive MI/CBT condition were selected at random to receive their treatment 'live' (i.e. delivered by a psychologist) or via a computer-based program (with brief weekly input from a psychologist). Depression, alcohol/cannabis use and hazardous substance use index scores measured at baseline, and 3, 6 and 12 months post-baseline assessment. (i) Depression responded better to intensive MI/CBT compared to BI alone, with 'live' treatment demonstrating a strong short-term beneficial effect which was matched by computer-based treatment at 12-month follow-up; (ii) problematic alcohol use responded well to BI alone and even better to the intensive MI/CBT intervention; (iii) intensive MI/CBT was significantly better than BI alone in reducing cannabis use and hazardous substance use, with computer-based therapy showing the largest treatment effect. Computer-based treatment, targeting both depression and substance use simultaneously, results in at least equivalent 12-month outcomes relative to a 'live' intervention. For clinicians treating people with comorbid depression and alcohol problems, BIs addressing both issues appear to be an appropriate and efficacious treatment option. Primary care of those with comorbid depression and cannabis use problems could involve computer-based integrated interventions for depression and cannabis use, with brief regular contact with the clinician to check on progress.

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

Investigation of the contextual interference effect in the manipulation of the motor parameter of over-all force.

PubMed

Goodwin, J E; Meeuwsen, H J

1996-12-01

This investigation examined the contextual interference effect when manipulating over-all force in a golf-putting task. Undergraduate women (N = 30) were randomly assigned to a Random, Blocked-Random, or Blocked practice condition and practiced golf putting from distances of 2.43 m, 3.95 m, and 5.47 m during acquisition. Subjects in the Random condition practiced trials in a quasirandom sequence and those in the Blocked-Random condition practiced trials initially in a blocked sequence with the remainder of the trials practiced in a quasirandom sequence. In the Blocked condition subjects practiced trials in a blocked sequence. A 24-hr. transfer test consisted of 30 trials with 10 trials each from 1.67 m, 3.19 m, and 6.23 m. Transfer scores supported the Magill and Hall (1990) hypothesis that, when task variations involve learning parameters of a generalized motor program, the benefit of random practice over blocked practice would not be found.

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.

Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.

PubMed

Mujugira, Andrew; Baeten, Jared M; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R; Barnes, Linda; Campbell, James D; Wangisi, Jonathan; Tappero, Jordan W; Bukusi, Elizabeth; Cohen, Craig R; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Were, Edwin; Fife, Kenneth H; Kiarie, James; Farquhar, Carey; John-Stewart, Grace; Kidoguchi, Lara; Panteleeff, Dana; Krows, Meighan; Shah, Heena; Revall, Jennifer; Morrison, Susan; Ondrejcek, Lisa; Ingram, Charlotte; Coombs, Robert W; Lingappa, Jairam R; Celum, Connie

2011-01-01

Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort. HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months. From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40) and (26-39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/µL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease. Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245).

Random matrix theory and cross-correlations in global financial indices and local stock market indices

NASA Astrophysics Data System (ADS)

Nobi, Ashadun; Maeng, Seong Eun; Ha, Gyeong Gyun; Lee, Jae Woo

2013-02-01

We analyzed cross-correlations between price fluctuations of global financial indices (20 daily stock indices over the world) and local indices (daily indices of 200 companies in the Korean stock market) by using random matrix theory (RMT). We compared eigenvalues and components of the largest and the second largest eigenvectors of the cross-correlation matrix before, during, and after the global financial the crisis in the year 2008. We find that the majority of its eigenvalues fall within the RMT bounds [ λ -, λ +], where λ - and λ + are the lower and the upper bounds of the eigenvalues of random correlation matrices. The components of the eigenvectors for the largest positive eigenvalues indicate the identical financial market mode dominating the global and local indices. On the other hand, the components of the eigenvector corresponding to the second largest eigenvalue are positive and negative values alternatively. The components before the crisis change sign during the crisis, and those during the crisis change sign after the crisis. The largest inverse participation ratio (IPR) corresponding to the smallest eigenvector is higher after the crisis than during any other periods in the global and local indices. During the global financial the crisis, the correlations among the global indices and among the local stock indices are perturbed significantly. However, the correlations between indices quickly recover the trends before the crisis.

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

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.

Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer.

PubMed

Leighl, Natasha B; Shepherd, Frances A; Kwong, Rita; Burkes, Ronald L; Feld, Ronald; Goodwin, Pamela J

2002-03-01

To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non-small-cell lung cancer. A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada's public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. The incremental survival benefit in the docetaxel arm over BSC was 2 months (P =.047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m(2), the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home. Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

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.

[Effectiveness of educational interventions conducted in latin america for the prevention of overweight and obesity in scholar children from 6-17 years old; a systematic review].

PubMed

Mancipe Navarrete, Jenny Alejandra; Garcia Villamil, Shanen Samanta; Correa Bautista, Jorge Enrique; Meneses-Echávez, José Francisco; González-Jiménez, Emilio; Schmidt Rio-Valle, Jacqueline

2014-10-03

Overweight and obesity are serious public health problem, which is specially among children populations. To determine the effectiveness of educational interventions conducted in Latino America for the prevention of overweight and obesity in scholar children from 6 to 17 years old. Metodology: MEDLINE, LILACS and EMBASE were searched between february and may 2014 to retrieve randomized controlled trials and longitudinal studies that evaluated the effects of educational interventions intended to retrieve randomized controlled trials and longitudinal studies aiming to prevent overweight and obesity among Latinoamerican children. Risk of bias was evaluated using the PEDro scale and the CASPe tool. Twenty one studies were included (n=12,092). Different types of educational interventions were identified, such as nutritional campaigns, physical activity practice and environmental changes. Mixed approaches combining nutritional campaigns, physical activity promotion and enviromental changes were the most effective interventions, since their results produced the largest improvements in the overweight and obesity of children. None evidence of reporting bias was observed. Educational interventions performed in the educational environment that combined an adequate nutrition and the promotion of physical activity practice, are more effective for preventing overweight and obesity in Latino American children, although familiar interventions are also encouraged approach, associated with better responses on the behavioral change in scholar children. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Evaluation of herbal cannabis characteristics by medical users: a randomized trial

PubMed Central

Ware, Mark A; Ducruet, Thierry; Robinson, Ann R

2006-01-01

Background Cannabis, in herbal form, is widely used as self-medication by patients with diseases such as HIV/AIDS and multiple sclerosis suffering from symptoms including pain, muscle spasticity, stress and insomnia. Valid clinical studies of herbal cannabis require a product which is acceptable to patients in order to maximize adherence to study protocols. Methods We conducted a randomized controlled crossover trial of 4 different herbal cannabis preparations among 8 experienced and authorized cannabis users with chronic pain. Preparations were varied with respect to grind size, THC content and humidity. Subjects received each preparation on a separate day and prepared the drug in their usual way in a dedicated and licensed clinical facility. They were asked to evaluate the products based on appearance (smell, colour, humidity, grind size, ease of preparation and overall appearance) and smoking characteristics (burn rate, hotness, harshness and taste). Five-point Likert scores were assigned to each characteristic. Scores were compared between preparations using ANOVA. Results Seven subjects completed the study, and the product with highest THC content (12%), highest humidity (14%) and largest grind size (10 mm) was rated highest overall. Significant differences were noted between preparations on overall appearance and colour (p = 0.003). Discussion While the small size of the study precludes broad conclusions, the study shows that medical cannabis users can appreciate differences in herbal product. A more acceptable cannabis product may increase recruitment and retention in clinical studies of medical cannabis. PMID:17101054

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.…

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.

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 importance of preservation of the ethical principle of equipoise in the design of clinical trials: relative impact of the methodological quality domains on the treatment effect in randomized controlled trials.

PubMed

Djulbegovic, Benjamin; Cantor, Alan; Clarke, Mike

2003-01-01

Previous research has identified methodological problems in the design and conduct of randomized trials that could, if left unaddressed, lead to biased results. In this report we discuss one such problem, inadequate control intervention, and argue that it can be by far the most important design characteristic of randomized trials in overestimating the effect of new treatments. Current guidelines for the design and reporting of randomized trials, such as the Consolidated Standards of Reporting Trials (CONSORT) statement, do not address the choice of the comparator intervention. We argue that an adequate control intervention can be selected if people designing a trial explicitly take into consideration the ethical principle of equipoise, also known as "the uncertainty principle."

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.

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

Effects of an Art-Based Curriculum on Clinical Trials Attitudes and Breast Cancer Prevention Knowledge

ERIC Educational Resources Information Center

Herman, Patricia M.; Larkey, Linda K.

2006-01-01

Although Latinos now comprise the largest minority in the U.S. population, they continue to be seriously underrepresented in clinical trials. A nonrandomized controlled study of an innovative community-developed clinical trial and breast cancer education program targeting Latinas tested whether use of an art-based curriculum could increase…

Costs and cost-effectiveness of a mental health intervention for war-affected young persons: decision analysis based on a randomized controlled trial

PubMed Central

McBain, Ryan K; Salhi, Carmel; Hann, Katrina; Salomon, Joshua A; Kim, Jane J; Betancourt, Theresa S

2016-01-01

Background: One billion children live in war-affected regions of the world. We conducted the first cost-effectiveness analysis of an intervention for war-affected youth in sub-Saharan Africa, as well as a broader cost analysis. Methods: The Youth Readiness Intervention (YRI) is a behavioural treatment for reducing functional impairment associated with psychological distress among war-affected young persons. A randomized controlled trial was conducted in Freetown, Sierra Leone, from July 2012 to July 2013. Participants (n = 436, aged 15–24) were randomized to YRI (n = 222) or care as usual (n = 214). Functional impairment was indexed by the World Health Organization Disability Assessment Scale; scores were converted to quality-adjusted life years (QALYs). An ‘ingredients approach’ estimated financial and economic costs, assuming a societal perspective. Incremental cost-effectiveness ratios (ICERs) were also expressed in terms of gains across dimensions of mental health and schooling. Secondary analyses explored whether intervention effects were largest among those worst-off (upper quartile) at baseline. Results: Retention at 6-month follow-up was 85% (n = 371). The estimated economic cost of the intervention was $104 per participant. Functional impairment was lower among YRI recipients, compared with controls, following the intervention but not at 6-month follow-up, and yielded an ICER of $7260 per QALY gained. At 8-month follow-up, teachers’ interviews indicated that YRI recipients observed higher school enrolment [P < 0.001, odds ratio (OR) 8.9], denoting a cost of $431 per additional school year gained, as well as better school attendance (P = 0.007, OR 34.9) and performance (P = 0.03, effect size = −1.31). Secondary analyses indicated that the intervention was cost-effective among those worst-off at baseline, yielding an ICER of $3564 per QALY gained. Conclusions: The YRI is not cost-effective at a willingness-to-pay threshold of three times average gross domestic product per capita. However, results indicate that the YRI translated into a range of benefits, such as improved school enrolment, not captured by cost-effectiveness analysis. We also outline areas for modification to improve cost-effectiveness in future trials. Trial Registration: clinicaltrials.gov Identifier: RPCGA-YRI-21003 PMID:26345320

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

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Are cannabinoids an alternative for cachexia-anorexia syndrome in patients with advanced cancer?

PubMed

Cabeza, Claudia; Corsi, Oscar; Pérez-Cruz, Pedro

2017-12-29

Cachexia and anorexia are among the most frequent symptoms in patients with cancer. Cannabinoids have been used in patients with advanced cancer; however, their role is still controversial. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, and generated a summary of findings table using the GRADE approach. We identified ten systematic reviews including three studies overall, of which two were randomized trials. We concluded it is not clear whether cannabinoids have any positive effect on increasing weight because the certainty of the evidence is very low. They might not have any effect on appetite, and are probably associated to frequent adverse effects.

Reporting of participant flow diagrams in published reports of randomized trials

PubMed Central

2011-01-01

Background 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. Methods 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. Results 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. Conclusions Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented. PMID:22141446

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.

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 American Heart Association, Inc.

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

PubMed

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

2016-11-01

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

Improving Language Comprehension in Preschool Children with Language Difficulties: A Cluster Randomized Trial

ERIC Educational Resources Information Center

Hagen, Åste M.; Melby-Lervåg, Monica; Lervåg, Arne

2017-01-01

Background: Children with language comprehension difficulties are at risk of educational and social problems, which in turn impede employment prospects in adulthood. However, few randomized trials have examined how such problems can be ameliorated during the preschool years. Methods: We conducted a cluster randomized trial in 148 preschool…

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…

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

Weighted re-randomization tests for minimization with unbalanced allocation.

PubMed

Han, Baoguang; Yu, Menggang; McEntegart, Damian

2013-01-01

Re-randomization test has been considered as a robust alternative to the traditional population model-based methods for analyzing randomized clinical trials. This is especially so when the clinical trials are randomized according to minimization, which is a popular covariate-adaptive randomization method for ensuring balance among prognostic factors. Among various re-randomization tests, fixed-entry-order re-randomization is advocated as an effective strategy when a temporal trend is suspected. Yet when the minimization is applied to trials with unequal allocation, fixed-entry-order re-randomization test is biased and thus compromised in power. We find that the bias is due to non-uniform re-allocation probabilities incurred by the re-randomization in this case. We therefore propose a weighted fixed-entry-order re-randomization test to overcome the bias. The performance of the new test was investigated in simulation studies that mimic the settings of a real clinical trial. The weighted re-randomization test was found to work well in the scenarios investigated including the presence of a strong temporal trend. Copyright © 2013 John Wiley & Sons, Ltd.

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 (31 July 2012). Full trial first randomization: 19 September 2012. PMID:24304689

Communicating data about the benefits and harms of treatment: a randomized trial.

PubMed

Woloshin, Steven; Schwartz, Lisa M

2011-07-19

Despite limited evidence, it is often asserted that natural frequencies (for example, 2 in 1000) are the best way to communicate absolute risks. To compare comprehension of treatment benefit and harm when absolute risks are presented as natural frequencies, percents, or both. Parallel-group randomized trial with central allocation and masking of investigators to group assignment, conducted through an Internet survey in September 2009. (ClinicalTrials.gov registration number: NCT00950014) National sample of U.S. adults randomly selected from a professional survey firm's research panel of about 30,000 households. 2944 adults aged 18 years or older (all with complete follow-up). Tables presenting absolute risks in 1 of 5 numeric formats: natural frequency (x in 1000), variable frequency (x in 100, x in 1000, or x in 10,000, as needed to keep the numerator >1), percent, percent plus natural frequency, or percent plus variable frequency. Comprehension as assessed by 18 questions (primary outcome) and judgment of treatment benefit and harm. The average number of comprehension questions answered correctly was lowest in the variable frequency group and highest in the percent group (13.1 vs. 13.8; difference, 0.7 [95% CI, 0.3 to 1.1]). The proportion of participants who "passed" the comprehension test (≥13 correct answers) was lowest in the natural and variable frequency groups and highest in the percent group (68% vs. 73%; difference, 5 percentage points [CI, 0 to 10 percentage points]). The largest format effect was seen for the 2 questions about absolute differences: the proportion correct in the natural frequency versus percent groups was 43% versus 72% (P < 0.001) and 73% versus 87% (P < 0.001). Even when data were presented in the percent format, one third of participants failed the comprehension test. Natural frequencies are not the best format for communicating the absolute benefits and harms of treatment. The more succinct percent format resulted in better comprehension: Comprehension was slightly better overall and notably better for absolute differences. Attorney General Consumer and Prescriber Education grant program, the Robert Wood Johnson Pioneer Program, and the National Cancer Institute.

Mediation of Short and Longer Term Effects of an Intervention Program to Enhance Resilience in Immigrants from Mainland China to Hong Kong

PubMed Central

Yu, Nancy X.; Lam, T. H.; Liu, Iris K. F.; Stewart, Sunita M.

2015-01-01

Few clinical trials report on the active intervention components that result in outcome changes, although this is relevant to further improving efficacy and adapting effective programs to other populations. This paper presents follow-up analyses of a randomized controlled trial to enhance adaptation by increasing knowledge and personal resilience in two separate brief interventions with immigrants from Mainland China to Hong Kong (Yu et al., 2014b). The present paper extends our previous one by reporting on the longer term effect of the interventions on personal resilience, and examining whether the Resilience intervention worked as designed to enhance personal resilience. The four-session intervention targeted at self-efficacy, positive thinking, altruism, and goal setting. In this randomized controlled trial, 220 immigrants were randomly allocated to three arms: Resilience, Information (an active control arm), and Control arms. Participants completed measures of the four active components (self-efficacy, positive thinking, altruism, and goal setting) at baseline and immediately after the intervention. Personal resilience was assessed at baseline, post-intervention, and 3- and 6-month follow-ups. The results showed that the Resilience arm had greater increases in the four active components post-intervention. Changes in each of the four active components at the post-intervention assessment mediated enhanced personal resilience at the 3-month follow-up in the Resilience arm. Changes in self-efficacy and goal setting showed the largest effect size, and altruism showed the smallest. The arm effects of the Resilience intervention on enhanced personal resilience at the 6-month follow-up were mediated by increases of personal resilience post-intervention (Resilience vs. Control) and at the 3-month follow-up (Resilience vs. Information). These findings showed that these four active components were all mediators in this Resilience intervention. Our results of the effects of short term increases in personal resilience on longer term increase in personal resilience in some models suggest how changes in intervention outcomes might persist over time. PMID:26640446

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.

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

PubMed

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

2016-11-01

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

School-based programmes for preventing smoking.

PubMed

Thomas, R; Perera, R

2006-07-19

Smoking rates in adolescents are rising in some countries. Helping young people to avoid starting smoking is a widely endorsed goal of public health, but there is uncertainty about how to do this. Schools provide a route for communicating with a large proportion of young people, and school-based programmes for smoking prevention have been widely developed and evaluated. To review all randomized controlled trials of behavioural interventions in schools to prevent children (aged 5 to12) and adolescents (aged 13 to18) starting smoking. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Tobacco Addiction Group's Specialized Register, MEDLINE, EMBASE, PsyclNFO, ERIC, CINAHL, Health Star, Dissertation Abstracts and studies identified in the bibliographies of articles. Individual MEDLINE searches were made for 133 authors who had undertaken randomized controlled trials in this area. Types of studies: those in which individual students, classes, schools, or school districts were randomized to the intervention or control groups and followed for at least six months. Children (aged 5 to12) or adolescents (aged 13 to18) in school settings. Types of interventions: Classroom programmes or curricula, including those with associated family and community interventions, intended to deter use of tobacco. We included programmes or curricula that provided information, those that used social influences approaches, those that taught generic social competence, and those that included interventions beyond the school into the community. We included programmes with a drug or alcohol focus if outcomes for tobacco use were reported. Types of outcome measures: Prevalence of non-smoking at follow up among those not smoking at baseline. We did not require biochemical validation of self-reported tobacco use for study inclusion. We assessed whether identified citations were randomized controlled trials. We assessed the quality of design and execution, and abstracted outcome data. Because of the marked heterogeneity of design and outcomes, we computed pooled estimates only for those trials that could be analyzed together and for which statistical data were available. We predominantly synthesized the data using narrative systematic review. We grouped studies by intervention method (information; social competence; social influences; combined social influences/social competence; multi-modal programmes). Within each group, we placed them into three categories (low, medium and high risk of bias) according to validity using quality criteria for reported study design. Of the 94 randomized controlled trials identified, we classified 23 as category one (most valid). There was one category one study of information-giving and two of teaching social comeptence. There were thirteen category one studies of social influences interventions. Of these, nine found some positive effect of intervention on smoking prevalence, and four failed to detect an effect on smoking prevalence. The largest and most rigorous study, the Hutchinson Smoking Prevention Project, found no long-term effect of an intensive eight-year programme on smoking behaviour. There were three category one RCTs of combined social influences and social competence interventions: one provided significant results and one only for instruction by health educators compared to self-instruction. There was a lack of high quality evidence about the effectiveness of combinations of social influences and social competence approaches. There was one category one study providing data on social influences compared with information giving. There were four category one studies of multi-modal approaches but they provided limited evidence about the effectiveness of multi-modal approaches including community initiatives. There is one rigorous test of the effects of information-giving about smoking. There are well-conducted randomized controlled trials to test the effects of social influences interventions: in half of the group of best quality studies those in the intervention group smoke less than those in the control, but many studies failed to detect an effect of the intervention. There are only three high quality RCTs which test the effectiveness of combinations of social influences and social competence interventions, and four which test multi-modal interventions; half showed significant positive results.

Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.

PubMed

Zinman, Bernard; Inzucchi, Silvio E; Lachin, John M; Wanner, Christoph; Fitchett, David; Kohler, Sven; Mattheus, Michaela; Woerle, Hans J; Broedl, Uli C; Johansen, Odd Erik; Albers, Gregory W; Diener, Hans Christoph

2017-05-01

In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89-1.56; P =0.26). We further investigated cerebrovascular events. Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81-1.45; P =0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676. © 2017 The Authors.

Biorepository for Selenium and Vitamin E Cancer Prevention Trial (SELECT) | Division of Cancer Prevention

Cancer.gov

As the largest prostate cancer prevention trial ever undertaken, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) has assembled a substantial biorepository of specimens. To help make SELECT resources available to a wider research community, NCI and the Southwest Oncology Group are developing a plan for prostate cancer biology and nutritional science and

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…

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation

ERIC Educational Resources Information Center

Acosta, Joie D.; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S.

2016-01-01

Restorative practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this article describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI)…

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.

Quality of surgical randomized controlled trials for acute cholecystitis: assessment based on CONSORT and additional check items.

PubMed

Shikata, Satoru; Nakayama, Takeo; Yamagishi, Hisakazu

2008-01-01

In this study, we conducted a limited survey of reports of surgical randomized controlled trials, using the consolidated standards of reporting trials (CONSORT) statement and additional check items to clarify problems in the evaluation of surgical reports. A total of 13 randomized trials were selected from two latest review articles on biliary surgery. Each randomized trial was evaluated according to 28 quality measures that comprised items from the CONSORT statement plus additional items. Analysis focused on relationships between the quality of each study and the estimated effect gap ("pooled estimate in meta-analysis" -- "estimated effect of each study"). No definite relationships were found between individual study quality and the estimated effect gap. The following items could have been described but were not provided in almost all the surgical RCT reports: "clearly defined outcomes"; "details of randomization"; "participant flow charts"; "intention-to-treat analysis"; "ancillary analyses"; and "financial conflicts of interest". The item, "participation of a trial methodologist in the study" was not found in any of the reports. Although the quality of reporting trials is not always related to a biased estimation of treatment effect, the items used for quality measures must be described to enable readers to evaluate the quality and applicability of the reporting. Further development of an assessment tool is needed for items specific to surgical randomized controlled trials.

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.

Disappointment and adherence among parents of newborns allocated to the control group: a qualitative study of a randomized clinical trial.

PubMed

Meinich Petersen, Sandra; Zoffmann, Vibeke; Kjærgaard, Jesper; Graff Stensballe, Lone; Graff Steensballe, Lone; Greisen, Gorm

2014-04-15

When a child participates in a clinical trial, informed consent has to be given by the parents. Parental motives for participation are complex, but the hope of getting a new and better treatment for the child is important. We wondered how parents react when their child is allocated to the control group of a randomized controlled trial, and how it will affect their future engagement in the trial. We included parents of newborns randomized to the control arm in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study is a randomized clinical trial investigating the non-specific effects of early BCG-vaccine to healthy neonates. Randomization is performed immediately after birth and parents are not blinded to the allocation. We set up a semi-structured focus group with six parents from four families. Afterwards we telephone-interviewed another 19 mothers to achieve saturation. Thematic analysis was used to identify themes across the data sets. The parents reported good understanding of the randomization process. Their most common reaction to allocation was disappointment, though relief was also seen. A model of reactions to being allocated to the control group was developed based on the participants' different positions along two continuities from 'Our participation in trial is not important' to 'Our participation in trial is important', and 'Vaccine not important to us' to 'Vaccine important to us'. Four very disappointed families had thought of getting the vaccine elsewhere, and one had actually had their child vaccinated. All parents involved in the focus group and the telephone interviews wanted to participate in the follow-ups planned for the Calmette study. This study identified an almost universal experience of disappointment among parents of newborns who were randomized to the control group, but also a broad expression of understanding and accepting the idea of randomization. The trial staff might use the model of reactions in understanding the parents' disappointment and in this way support their motives for participation. A generalized version might be applicable across randomized controlled trials at large. The Calmette study is registered in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

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

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.

The role of NIV in chronic hypercapnic COPD following an acute exacerbation: the importance of patient selection?

PubMed

Duiverman, Marieke L; Windisch, Wolfram; Storre, Jan H; Wijkstra, Peter J

2016-04-01

Recently, clear benefits have been shown from long-term noninvasive ventilation (NIV) in stable chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure. In our opinion, these benefits are confirmed and nocturnal NIV using sufficiently high inspiratory pressures should be considered in COPD patients with chronic hypercapnic respiratory failure in stable disease, preferably combined with pulmonary rehabilitation. In contrast, clear benefits from (continuing) NIV at home after an exacerbation in patients who remain hypercapnic have not been shown. In this review we will discuss the results of five trials investigating the use of home nocturnal NIV in patients with prolonged hypercapnia after a COPD exacerbation with acute hypercapnic respiratory failure. Although some uncontrolled trials might have shown some benefits of this therapy, the largest randomized controlled trial did not show benefits in terms of hospital readmission or death. However, further studies are necessary to select the patients that optimally benefit, select the right moment to initiate home NIV, select the optimal ventilatory settings, and to choose optimal follow up programmes. Furthermore, there is insufficient knowledge about the optimal ventilatory settings in the post-exacerbation period. Finally, we are not well informed about exact reasons for readmission in patients on NIV, the course of the exacerbation and the treatment instituted. A careful follow up might probably be necessary to prevent deterioration on NIV early. © The Author(s), 2016.

Rapid response systems.

PubMed

Lyons, Patrick G; Edelson, Dana P; Churpek, Matthew M

2018-07-01

Rapid response systems are commonly employed by hospitals to identify and respond to deteriorating patients outside of the intensive care unit. Controversy exists about the benefits of rapid response systems. We aimed to review the current state of the rapid response literature, including evolving aspects of afferent (risk detection) and efferent (intervention) arms, outcome measurement, process improvement, and implementation. Articles written in English and published in PubMed. Rapid response systems are heterogeneous, with important differences among afferent and efferent arms. Clinically meaningful outcomes may include unexpected mortality, in-hospital cardiac arrest, length of stay, cost, and processes of care at end of life. Both positive and negative interventional studies have been published, although the two largest randomized trials involving rapid response systems - the Medical Early Response and Intervention Trial (MERIT) and the Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients (EPOCH) trial - did not find a mortality benefit with these systems, albeit with important limitations. Advances in monitoring technologies, risk assessment strategies, and behavioral ergonomics may offer opportunities for improvement. Rapid responses may improve some meaningful outcomes, although these findings remain controversial. These systems may also improve care for patients at the end of life. Rapid response systems are expected to continue evolving with novel developments in monitoring technologies, risk prediction informatics, and work in human factors. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

A new mosaic method for three-dimensional surface

NASA Astrophysics Data System (ADS)

Yuan, Yun; Zhu, Zhaokun; Ding, Yongjun

2011-08-01

Three-dimensional (3-D) data mosaic is a indispensable link in surface measurement and digital terrain map generation. With respect to the mosaic problem of the local unorganized cloud points with rude registration and mass mismatched points, a new mosaic method for 3-D surface based on RANSAC is proposed. Every circular of this method is processed sequentially by random sample with additional shape constraint, data normalization of cloud points, absolute orientation, data denormalization of cloud points, inlier number statistic, etc. After N random sample trials the largest consensus set is selected, and at last the model is re-estimated using all the points in the selected subset. The minimal subset is composed of three non-colinear points which form a triangle. The shape of triangle is considered in random sample selection in order to make the sample selection reasonable. A new coordinate system transformation algorithm presented in this paper is used to avoid the singularity. The whole rotation transformation between the two coordinate systems can be solved by twice rotations expressed by Euler angle vector, each rotation has explicit physical means. Both simulation and real data are used to prove the correctness and validity of this mosaic method. This method has better noise immunity due to its robust estimation property, and has high accuracy as the shape constraint is added to random sample and the data normalization added to the absolute orientation. This method is applicable for high precision measurement of three-dimensional surface and also for the 3-D terrain mosaic.

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

Coordination and Management of Multisite Complementary and Alternative Medicine (CAM) Therapies: Experience from a Multisite Reflexology Intervention Trial

PubMed Central

Rahbar, Mohammad H.; Wyatt, Gwen; Sikorskii, Alla; Victorson, David; Ardjomand-Hessabi, Manouchehr

2011-01-01

Background Multisite randomized clinical trials allow for increased research collaboration among investigators and expedite data collection efforts. As a result, government funding agencies typically look favorably upon this approach. As the field of complementary and alternative medicine (CAM) continues to evolve, so do increased calls for the use of more rigorous study design and trial methodologies, which can present challenges for investigators. Purpose To describe the processes involved in the coordination and management of a multisite randomized clinical trial of a CAM intervention. Methods Key aspects related to the coordination and management of a multisite CAM randomized clinical trial are presented, including organizational and site selection considerations, recruitment concerns and issues related to data collection and randomization to treatment groups. Management and monitoring of data, as well as quality assurance procedures are described. Finally, a real world perspective is shared from a recently conducted multisite randomized clinical trial of reflexology for women diagnosed with advanced breast cancer. Results The use of multiple sites in the conduct of CAM-based randomized clinical trials can provide an efficient, collaborative and robust approach to study coordination and data collection that maximizes efficiency and ensures the quality of results. Conclusions Multisite randomized clinical trial designs can offer the field of CAM research a more standardized and efficient approach to examine the effectiveness of novel therapies and treatments. Special attention must be given to intervention fidelity, consistent data collection and ensuring data quality. Assessment and reporting of quantitative indicators of data quality should be required. PMID:21664296

The acute effect of exercise modality and nutrition manipulations on post-exercise resting energy expenditure and respiratory exchange ratio in women: a randomized trial.

PubMed

Wingfield, Hailee L; Smith-Ryan, Abbie E; Melvin, Malia N; Roelofs, Erica J; Trexler, Eric T; Hackney, Anthony C; Weaver, Mark A; Ryan, Eric D

2015-06-01

The purpose of this study was to examine the effect of exercise modality and pre-exercise carbohydrate (CHO) or protein (PRO) ingestion on post-exercise resting energy expenditure (REE) and respiratory exchange ratio (RER) in women. Twenty recreationally active women (mean ± SD; age 24.6 ± 3.9 years; height 164.4 ± 6.6 cm; weight 62.7 ± 6.6 kg) participated in this randomized, crossover, double-blind study. Each participant completed six exercise sessions, consisting of three exercise modalities: aerobic endurance exercise (AEE), high-intensity interval running (HIIT), and high-intensity resistance training (HIRT); and two acute nutritional interventions: CHO and PRO. Salivary samples were collected before each exercise session to determine estradiol-β-17 and before and after to quantify cortisol. Post-exercise REE and RER were analyzed via indirect calorimetry at the following: baseline, immediately post (IP), 30 minutes (30 min) post, and 60 minutes (60 min) post exercise. A mixed effects linear regression model, controlling for estradiol, was used to compare mean longitudinal changes in REE and RER. On average, HIIT produced a greater REE than AEE and HIRT ( p < 0.001) post exercise. Effects of AEE and HIRT were not significantly different for post-exercise REE ( p = 0.1331). On average, HIIT produced lower RER compared to either AEE or HIRT after 30 min ( p < 0.001 and p = 0.0169, respectively) and compared to AEE after 60 min ( p = 0.0020). On average, pre-exercise PRO ingestion increased post-exercise REE ( p = 0.0076) and decreased post-exercise RER ( p < 0.0001) compared to pre-exercise CHO ingestion. HIIT resulted in the largest increase in REE and largest reduction in RER.

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…

RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

2015-08-01

Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool , a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature.

Transabdominal amnioinfusion for preterm premature rupture of membranes: a systematic review and metaanalysis of randomized and observational studies.

PubMed

Porat, Shay; Amsalem, Hagai; Shah, Prakesh S; Murphy, Kellie E

2012-11-01

The purpose of this study was to review systematically the efficacy of transabdominal amnioinfusion (TA) in early preterm premature rupture of membranes (PPROM). We conducted a literature search of EMBASE, MEDLINE, and ClinicalTrials.gov databases and identified studies in which TA was used in cases of proven PPROM and oligohydramnios. Risk of bias was assessed for observational studies and randomized controlled trials. Primary outcomes were latency period and perinatal mortality rates. Four observational studies (n = 147) and 3 randomized controlled trials (n = 165) were eligible. Pooled latency period was 14.4 (range, 8.2-20.6) and 11.41 (range -3.4 to 26.2) days longer in the TA group in the observational and the randomized controlled trials, respectively. Perinatal mortality rates were reduced among the treatment groups in both the observational studies (odds ratio, 0.12; 95% confidence interval, 0.02-0.61) and the randomized controlled trials (odds ratio, 0.33; 95% confidence interval, 0.10-1.12). Serial TA for early PPROM may improve early PPROM-associated morbidity and mortality rates. Additional adequately powered randomized control trials are needed. Copyright © 2012 Mosby, Inc. All rights reserved.

Clinical trials in crisis: four simple methodologic fixes

PubMed Central

Vickers, Andrew J.

2014-01-01

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the “Sensible Guidelines Group” seek to push back against current trends in clinical trials, arguing that all aspects of trials - including design, approval, conduct, monitoring, analysis and dissemination - should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs and increasing patient acceptability by dramatically reducing eligibility criteria - often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal - and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients and we need to ensure that they continue to do so. PMID:25278228

Clinical trials in crisis: Four simple methodologic fixes.

PubMed

Vickers, Andrew J

2014-12-01

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet, concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the "Sensible Guidelines Group" seek to push back against current trends in clinical trials, arguing that all aspects of trials-including design, approval, conduct, monitoring, analysis, and dissemination-should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs, and increasing patient acceptability by dramatically reducing eligibility criteria-often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal-and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet, the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients, and we need to ensure that they continue to do so. © The Author(s) 2014.

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

The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: a Global Allergy and Asthma European Network (GA(2)LEN) article.

PubMed

Bousquet, Philippe J; Calderón, Moisés A; Demoly, Pascal; Larenas, Désirée; Passalacqua, Giovanni; Bachert, Claus; Brozek, Jan; Canonica, G Walter; Casale, Thomas; Fonseca, Joao; Dahl, Ronald; Durham, Stephen R; Merk, Hans; Worm, Margitta; Wahn, Ulrich; Zuberbier, Torsten; Schünemann, Holger J; Bousquet, Jean

2011-01-01

Randomized trials provide evidence to inform treatment decisions. The Consolidated Standards of Reporting Trials (CONSORT) Statement is a set of recommendations for the reporting of trials. We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria. The reporting of the procedure, randomization, dropouts, strict conduct of intention-to-treat (ITT) analysis, and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy (SLIT) blind, placebo-controlled randomized trials published between 1996 and 2009 in English. One subcutaneous immunotherapy (2.2%) and 3 SLIT (6.6%) trials met CONSORT Statement criteria. These were used for the registration of sublingual tablets to the European Medicines Agency. In subcutaneous immunotherapy, 16 (35%) studies reported a CONSORT flow chart, and 12 (26%) provided a description of dropouts. Adequate randomization was reported in 9 (35%) studies, and incomplete randomization was reported in 15 (33%). Power analysis was reported in 15 (33%) studies. In SLIT, 20 (42%) studies reported a CONSORT flow chart, and 16 (32%) a description of dropouts. ITT analysis was carried out in 1 (2.2%) SLIT study, and a modified ITT analysis was used in 1 (2.2%) subcutaneous immunotherapy study and 2 (4.4%) SLIT studies. Adequate randomization was reported in 6 (12%) studies, and incomplete randomization was reported in 16 (32%). Power analysis was reported in 15 (27%) studies. As in other areas of medicine, the quality of reporting of most immunotherapy trials is low, and only 4.2% of SLIT randomized controlled trials met all of the criteria of the CONSORT Statement. Use of the CONSORT criteria should be encouraged. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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

PubMed

Roper, Nitin; Korenstein, Deborah

2015-10-01

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

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia

PubMed Central

Shenoy, Erica S.; Huang, Mingshu; Kuhlen, James L.; Ware, Winston A.; Parker, Robert A.; Walensky, Rochelle P.

2016-01-01

Background Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral β-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. Objective To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Design Retrospective cohort. Participants Adult inpatients with MSSA bacteremia, January 2009 through October 2013. Main Measures The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. Key Results Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). Conclusions Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients. PMID:27438379

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

PubMed

Blumenthal, Kimberly G; Shenoy, Erica S; Huang, Mingshu; Kuhlen, James L; Ware, Winston A; Parker, Robert A; Walensky, Rochelle P

2016-01-01

Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral β-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Retrospective cohort. Adult inpatients with MSSA bacteremia, January 2009 through October 2013. The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.

The Recombinant Bacille Calmette-Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing.

PubMed

Nieuwenhuizen, Natalie E; Kulkarni, Prasad S; Shaligram, Umesh; Cotton, Mark F; Rentsch, Cyrill A; Eisele, Bernd; Grode, Leander; Kaufmann, Stefan H E

2017-01-01

The only licensed vaccine against tuberculosis (TB), bacille Calmette-Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes . Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔ ureC :: hly (VPM1002) promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

Clinical Knowledge from Observational Studies: Everything You Wanted to Know but Were Afraid to Ask.

PubMed

Gershon, Andrea S; Jafarzadeh, S Reza; Wilson, Kevin C; Walkey, Allan J

2018-05-07

Well-done randomized trials provide accurate estimates of treatment effect by producing groups that are similar on all measures except for the intervention of interest. However, inferences of efficacy in tightly-controlled experimental settings may not translate into similar effectiveness in real-world settings. Observational studies generally enable inferences over a wider range of patient characteristics and evaluation of a broader range of outcomes over a longer period than randomized trials. However, clinicians are often reluctant to incorporate the findings of observational studies into clinical practice. Reason for uncertainty regarding observational studies include a lack of familiarity with observational research methods, occasional disagreements between results of observational studies and randomized trials, the perceived risk of spurious results from systematic bias, and prior teaching that randomized trials are the most reliable source of medical evidence. We propose that a better understanding of observational research will enhance clinicians' ability to distinguish reliable observational studies from those that are subjected to biases and, therefore, provide more confidence to apply observational research results into clinical practice when appropriate. Herein, we explain why observational studies may be perceived as less conclusive than randomized trials, address situations in which observational research and randomized trials produced different findings, and provide information on observational study design so that quality can be evaluated. We conclude that observational research is a valuable source of medical evidence and that clinical action is strongest when supported by both high quality observational studies and randomized trials.

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

2015-01-01

Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

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.

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.

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

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.

[Non-randomized evaluation studies (TREND)].

PubMed

Vallvé, Carles; Artés, Maite; Cobo, Erik

2005-12-01

Nonrandomized intervention trials are needed when randomized clinical trials cannot be performed. To report the results from nonrandomized intervention studies transparently, the TREND (Transparent Reporting of Evaluations with Nonrandomized Designs) checklist should be used. This implies that nonrandomized studies should follow the remaining methodological tools usually employed in randomized trials and that the uncertainty introduced by the allocation mechanism should be explicitly reported and, if possible, quantified.

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…

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.

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.

Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study.

PubMed

Baber, Usman; Dangas, George; Cohen, David J; Gibson, C Michael; Mehta, Shamir R; Angiolillo, Dominick J; Pocock, Stuart J; Krucoff, Mitchell W; Kastrati, Adnan; Ohman, E Magnus; Steg, Philippe Gabriel; Badimon, Juan; Zafar, M Urooj; Chandrasekhar, Jaya; Sartori, Samantha; Aquino, Melissa; Mehran, Roxana

2016-12-01

Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y 12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES. Copyright © 2016 Elsevier Inc. All rights reserved.

Dissemination of the Look AHEAD Lifestyle Intervention in the United States Air Force: Study Rationale, Design and Methods

PubMed Central

Krukowski, Rebecca A.; Hare, Marion E.; Talcott, Gerald W.; Johnson, Karen C.; Richey, Phyllis A.; Kocak, Mehmet; Balderas, Jennifer; Colvin, Lauren; Keller, Patrick L.; Waters, Teresa M.; Klesges, Robert C.

2014-01-01

Despite an increase in overweight and obesity similar to the civilian population, there have been few randomized controlled trials examining behavioral weight management interventions in the military settings. This paper describes the design, intervention development and analysis plan of the Fit Blue study, a randomized controlled behavioral weight loss trial taking place in the United States Air Force. This study compares two adapted versions of the efficacious Look AHEAD Intensive Lifestyle Intervention (ILI), a counselor-initiated condition and a self-paced condition. Also described are the unique steps required when conducting military-based health promotion research and adaptations made to the Look AHEAD intervention to accommodate the military environment. To our knowledge, this is the first translation of the Look AHEAD ILI in the military setting and one of the first translations of the ILI in general. If successful, this intervention could be disseminated to the entire U.S. Military as this project is designed to overcome the barriers and utilize the facilitators for weight loss that are unique to a military population. Programs validated in military populations can have a major public health impact given that with 1.4 million active duty personnel, the Department of Defense is the nation’s largest employer. However, while this intervention is designed for a military population and there are unique aspects of the military that may enhance weight loss interventions, the diversity of the study population should help inform obesity efforts in both civilian and military settings. PMID:25545025

Identifying inaccuracies on emergency medicine residency applications

PubMed Central

Katz, Eric D; Shockley, Lee; Kass, Lawrence; Howes, David; Tupesis, Janis P; Weaver, Christopher; Sayan, Osman R; Hogan, Victoria; Begue, Jason; Vrocher, Diamond; Frazer, Jackie; Evans, Timothy; Hern, Gene; Riviello, Ralph; Rivera, Antonio; Kinoshita, Keith; Ferguson, Edward

2005-01-01

Background Previous trials have showed a 10–30% rate of inaccuracies on applications to individual residency programs. No studies have attempted to corroborate this on a national level. Attempts by residency programs to diminish the frequency of inaccuracies on applications have not been reported. We seek to clarify the national incidence of inaccuracies on applications to emergency medicine residency programs. Methods This is a multi-center, single-blinded, randomized, cohort study of all applicants from LCME accredited schools to involved EM residency programs. Applications were randomly selected to investigate claims of AOA election, advanced degrees and publications. Errors were reported to applicants' deans and the NRMP. Results Nine residencies reviewed 493 applications (28.6% of all applicants who applied to any EM program). 56 applications (11.4%, 95%CI 8.6–14.2%) contained at least one error. Excluding "benign" errors, 9.8% (95% CI 7.2–12.4%), contained at least one error. 41% (95% CI 35.0–47.0%) of all publications contained an error. All AOA membership claims were verified, but 13.7% (95%CI 4.4–23.1%) of claimed advanced degrees were inaccurate. Inter-rater reliability of evaluations was good. Investigators were reluctant to notify applicants' dean's offices and the NRMP. Conclusion This is the largest study to date of accuracy on application for residency and the first such multi-centered trial. High rates of incorrect data were found on applications. This data will serve as a baseline for future years of the project, with emphasis on reporting inaccuracies and warning applicants of the project's goals. PMID:16105178

Geographic Clustering of Underage Drinking and the Influence of Community Characteristics

PubMed Central

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

2009-01-01

The aim of this paper was to examine the extent to which underage drinking clusters geographically in a sample of communities, and to investigate the manner in which community-level contexts are related to this process. We used data from a randomized community trial of underage drinking to provide the first quantitative estimates of the magnitude of the geographic clustering of underage drinking based upon pairwise odds ratios (PWORs). The Enforcing Underage Drinking Laws Randomized Community Trial provided data from repeated cross-sectional samples of youth aged 14-20 from 68 communities surveyed in 2004, 2006, and 2007 (n=18, 730). Past 30-day drinking, binge drinking, getting drunk, experiencing non-violent consequences as a result of drinking and making a purchase attempt all significantly clustered within-communities with PWORs ranging from 1.05 to 1.21. After adjustment for individual-level characteristics, results remained relatively unchanged. However, there was evidence that the magnitude of the clustering varied as a function of neighborhood disadvantage, neighborhood disorder, and family structure. Clustering of drunkenness and experiencing non-violent consequences as a result of drinking was greatest in the least economically disadvantaged and least disordered communities with the greatest percentage of married couple families. The clustering of making a purchase attempt, however, was greatest in more disordered communities, specifically the largest communities with the highest degree of residential mobility and housing density. These findings that clustering of underage drinking behaviors varies by community context has the potential for identifying the types of communities to target for underage drinking behavior-specific preventive interventions. PMID:19740611

Geographic clustering of underage drinking and the influence of community characteristics.

PubMed

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

2010-01-01

The aim of this paper was to examine the extent to which underage drinking clusters geographically in a sample of communities, and to investigate the manner in which community-level contexts are related to this process. We used data from a randomized community trial of underage drinking to provide the first quantitative estimates of the magnitude of the geographic clustering of underage drinking based upon pairwise odds ratios (PWORs). The Enforcing Underage Drinking Laws Randomized Community Trial provided data from repeated cross-sectional samples of youth aged 14-20 from 68 communities surveyed in 2004, 2006, and 2007 (n=18,730). Past 30-day drinking, binge drinking, getting drunk, experiencing non-violent consequences as a result of drinking and making a purchase attempt all significantly clustered within-communities with PWORs ranging from 1.05 to 1.21. After adjustment for individual-level characteristics, results remained relatively unchanged. However, there was evidence that the magnitude of the clustering varied as a function of neighborhood disadvantage, neighborhood disorder, and family structure. Clustering of drunkenness and experiencing non-violent consequences as a result of drinking was greatest in the least economically disadvantaged and least disordered communities with the greatest percentage of married-couple families. The clustering of making a purchase attempt, however, was greatest in more disordered communities, specifically the largest communities with the highest degree of residential mobility and housing density. These findings that clustering of underage drinking behaviors varies by community context has the potential for identifying the types of communities to target for underage drinking behavior-specific preventive interventions. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

International multicentre trial protocol to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest: the Thrombolysis in Cardiac Arrest (TROICA) Study.

PubMed

Spöhr, F; Arntz, H R; Bluhmki, E; Bode, C; Carli, P; Chamberlain, D; Danays, T; Poth, J; Skamira, C; Wenzel, V; Böttiger, B W

2005-05-01

Prehospital cardiac arrest has been associated with a very poor prognosis. Acute myocardial infarction and massive pulmonary embolism are the underlying causes of out-of-hospital cardiac arrest in 50-70% of patients. Although fibrinolysis is an effective treatment strategy for both myocardial infarction and pulmonary embolism, clinical experience for this therapy performed during resuscitation has been limited owing to the anticipated risk of severe bleeding complications. The TROICA study is planned as one of the largest randomized, double-blind, placebo-controlled trials to assess the efficacy and safety of prehospital thrombolytic therapy in cardiac arrest of presumed cardiac origin. Approximately 1000 patients with cardiac arrest will be randomized at approximately 60 international study centres to receive either a weight-adjusted dose of tenecteplase or placebo after the first dose of a vasopressor. Patients can be included if they are at least 18 years, presenting with a witnessed cardiac arrest of presumed cardiac origin, and if either basic life support had started within 10 min of onset and had been performed up to 10 min or advanced life support is started within 10 min of onset of cardiac arrest. Primary endpoint of the study is the 30-day survival rate, and the coprimary endpoint is hospital admission. Secondary endpoints are the return of spontaneous circulation (ROSC), survival after 24 h, survival to hospital discharge, and neurological performance. Safety endpoints include major bleeding complications and symptomatic intracranial haemorrhage.

Dissemination of the Look AHEAD intensive lifestyle intervention in the United States Air Force: study rationale, design and methods.

PubMed

Krukowski, Rebecca A; Hare, Marion E; Talcott, Gerald W; Johnson, Karen C; Richey, Phyllis A; Kocak, Mehmet; Balderas, Jennifer; Colvin, Lauren; Keller, Patrick L; Waters, Teresa M; Klesges, Robert C

2015-01-01

Despite an increase in overweight and obesity similar to the civilian population, there have been few randomized controlled trials examining behavioral weight management interventions in the military settings. This paper describes the design, intervention development and analysis plan of the Fit Blue study, a randomized controlled behavioral weight loss trial taking place in the United States Air Force. This study compares two adapted versions of the efficacious Look AHEAD Intensive Lifestyle Intervention (ILI), a counselor-initiated condition and a self-paced condition. Also described are the unique steps required when conducting military-based health promotion research and adaptations made to the Look AHEAD intervention to accommodate the military environment. To our knowledge, this is the first translation of the Look AHEAD ILI in the military setting and one of the first translations of the ILI in general. If successful, this intervention could be disseminated to the entire U.S. Military as this project is designed to overcome the barriers and utilize the facilitators for weight loss that are unique to a military population. Programs validated in military populations can have a major public health impact given that with 1.4 million active duty personnel, the Department of Defense is the nation's largest employer. However, while this intervention is designed for a military population and there are unique aspects of the military that may enhance weight loss interventions, the diversity of the study population should help inform obesity efforts in both civilian and military settings. Copyright © 2014 Elsevier Inc. All rights reserved.

Information management and complementary alternative medicine: the anatomy of information about CAMs through PubMed.

PubMed

Corrao, Salvatore; Argano, Christiano; Colomba, Daniela; Ippolito, Calogero; Gargano, Vincenzo; Arcoraci, Vincenzo; Licata, Giuseppe

2013-10-01

In recent years, there has been a growing interest about complementary and alternative medicine (CAM), and the use of CAM interventions has become more common among people. For these reasons, health professionals must be able to effectively manage information in this field of knowledge according to an evidence-based point of view. This study assessed the anatomy of the available information about CAMs using PubMed, to give practical instructions to manage information in this field. We also analyzed the anatomy of information according to each alternative medicine branch, narrow and broad search methods, subset filters for indexed-for-Medline and non-indexed citations, and different publication types including randomized controlled trials (RCTs) and meta-analyses. Our results demonstrated that the use of CAMs subset (supplied by PubMed search engine) leads to a great number of citations determining an information overload. Our data reveal that it would be more useful to search for the CAM separately, identifying specific items and study design. Moreover, we found the largest number of randomized clinical trials and meta-analyses related to herbal medicine and acupuncture, neither RCTs nor meta-analyses were available for bach and flower remedies, auriculoacupuncture, iridology, and pranotherapy. For the first time, our study gives a comprehensive view of the anatomy of information regarding CAMs and each branch of them. We suggest a methodological approach to face with searching information about this emerging issue from an evidence-based point of view. Finally, our data pointed out some "grey zones" since neither RCTs nor meta-analyses were available for some CAMs.

How do cardiorespiratory fitness improvements vary with physical training modality in heart failure patients? A quantitative guide

PubMed Central

Smart, Neil A

2013-01-01

BACKGROUND: Peak oxygen consumption (VO2) is the gold standard measure of cardiorespiratory fitness and a reliable predictor of survival in chronic heart failure patients. Furthermore, any form of physical training usually improves cardiorespiratory fitness, although the magnitude of improvement in peak VO2 may vary across different training prescriptions. OBJECTIVE: To quantify, and subsequently rank, the magnitude of improvement in peak VO2 for different physical training prescriptions using data from published meta-analyses and randomized controlled trials. METHODS: Prospective randomized controlled parallel trials and meta-analyses of exercise training in chronic heart failure patients that provided data on change in peak VO2 for nine a priori comparative analyses were examined. RESULTS: All forms of physical training were beneficial, although the improvement in peak VO2 varied with modality. High-intensity interval exercise yielded the largest increase in peak VO2, followed in descending order by moderate-intensity aerobic exercise, functional electrical stimulation, inspiratory muscle training, combined aerobic and resistance training, and isolated resistance training. With regard to setting, the present study was unable to determine whether outpatient or unsupervised home exercise provided greater benefits in terms of peak VO2 improvment. CONCLUSIONS: Interval exercise is not suitable for all patients, especially the high-intensity variety; however, when indicated, this form of exercise should be adopted to optimize peak VO2 adaptations. Other forms of activity, such as functional electrical stimulation, may be more appropriate for patients who are not capable of high-intensity interval training, especially for severely deconditioned patients who are initially unable to exercise. PMID:24294043

A pattern-mixture model approach for handling missing continuous outcome data in longitudinal cluster randomized trials.

PubMed

Fiero, Mallorie H; Hsu, Chiu-Hsieh; Bell, Melanie L

2017-11-20

We extend the pattern-mixture approach to handle missing continuous outcome data in longitudinal cluster randomized trials, which randomize groups of individuals to treatment arms, rather than the individuals themselves. Individuals who drop out at the same time point are grouped into the same dropout pattern. We approach extrapolation of the pattern-mixture model by applying multilevel multiple imputation, which imputes missing values while appropriately accounting for the hierarchical data structure found in cluster randomized trials. To assess parameters of interest under various missing data assumptions, imputed values are multiplied by a sensitivity parameter, k, which increases or decreases imputed values. Using simulated data, we show that estimates of parameters of interest can vary widely under differing missing data assumptions. We conduct a sensitivity analysis using real data from a cluster randomized trial by increasing k until the treatment effect inference changes. By performing a sensitivity analysis for missing data, researchers can assess whether certain missing data assumptions are reasonable for their cluster randomized trial. Copyright © 2017 John Wiley & Sons, Ltd.

Low power and type II errors in recent ophthalmology research.

PubMed

Khan, Zainab; Milko, Jordan; Iqbal, Munir; Masri, Moness; Almeida, David R P

2016-10-01

To investigate the power of unpaired t tests in prospective, randomized controlled trials when these tests failed to detect a statistically significant difference and to determine the frequency of type II errors. Systematic review and meta-analysis. We examined all prospective, randomized controlled trials published between 2010 and 2012 in 4 major ophthalmology journals (Archives of Ophthalmology, British Journal of Ophthalmology, Ophthalmology, and American Journal of Ophthalmology). Studies that used unpaired t tests were included. Power was calculated using the number of subjects in each group, standard deviations, and α = 0.05. The difference between control and experimental means was set to be (1) 20% and (2) 50% of the absolute value of the control's initial conditions. Power and Precision version 4.0 software was used to carry out calculations. Finally, the proportion of articles with type II errors was calculated. β = 0.3 was set as the largest acceptable value for the probability of type II errors. In total, 280 articles were screened. Final analysis included 50 prospective, randomized controlled trials using unpaired t tests. The median power of tests to detect a 50% difference between means was 0.9 and was the same for all 4 journals regardless of the statistical significance of the test. The median power of tests to detect a 20% difference between means ranged from 0.26 to 0.9 for the 4 journals. The median power of these tests to detect a 50% and 20% difference between means was 0.9 and 0.5 for tests that did not achieve statistical significance. A total of 14% and 57% of articles with negative unpaired t tests contained results with β > 0.3 when power was calculated for differences between means of 50% and 20%, respectively. A large portion of studies demonstrate high probabilities of type II errors when detecting small differences between means. The power to detect small difference between means varies across journals. It is, therefore, worthwhile for authors to mention the minimum clinically important difference for individual studies. Journals can consider publishing statistical guidelines for authors to use. Day-to-day clinical decisions rely heavily on the evidence base formed by the plethora of studies available to clinicians. Prospective, randomized controlled clinical trials are highly regarded as a robust study and are used to make important clinical decisions that directly affect patient care. The quality of study designs and statistical methods in major clinical journals is improving overtime, 1 and researchers and journals are being more attentive to statistical methodologies incorporated by studies. The results of well-designed ophthalmic studies with robust methodologies, therefore, have the ability to modify the ways in which diseases are managed. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Are diuretics effective for Ménière`s disease?

PubMed

Rosenbaum, Andrés; Winter, Matías

2018-03-28

Ménière`s disease is an inner ear disorder characterized by episodes of spontaneous vertigo, fluctuating hearing loss and tinnitus. Diuretics have been widely used for the treatment of attacks, but there is controversy about their effectiveness. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We identified three systematic reviews including nineteen studies overall, of which four were randomized trials. We concluded it is not clear whether diuretics lead to a symptomatic improvement of vertigo or an objective decrease in hearing loss in patients with Ménière`s disease, because the certainty of the evidence is very low.

Effects of Recombinant Human Growth Hormone for Osteoporosis: Systematic Review and Meta-Analysis.

PubMed

Atkinson, Hayden F; Moyer, Rebecca F; Yacoub, Daniel; Coughlin, Dexter; Birmingham, Trevor B

2017-03-01

Our objective was to evaluate the efficacy of recombinant human growth hormone (GH) on bone mineral density (BMD) in persons age 50 and older, with normal pituitary function, with or at risk for developing osteoporosis. We systematically reviewed randomized clinical trials (RCTs), searching six databases, and conducted meta-analyses to examine GH effects on BMD of the lumbar spine and femoral neck. Data for fracture incidence, bone metabolism biomarkers, and adverse events were also extracted and analysed. Thirteen RCTs met the eligibility criteria. Pooled effect sizes suggested no significant GH effect on BMD. Pooled effect sizes were largest, but nonsignificant, when compared to placebo. GH had a significant effect on several bone metabolism biomarkers. A significantly higher rate of adverse events was observed in the GH groups. Meta-analysis of RCTs suggests that GH treatment for persons with or at risk for developing osteoporosis results in very small, nonsignificant increases in BMD.

Evaluation of genotype x environment interactions in cotton using the method proposed by Eberhart and Russell and reaction norm models.

PubMed

Alves, R S; Teodoro, P E; Farias, F C; Farias, F J C; Carvalho, L P; Rodrigues, J I S; Bhering, L L; Resende, M D V

2017-08-17

Cotton produces one of the most important textile fibers of the world and has great relevance in the world economy. It is an economically important crop in Brazil, which is the world's fifth largest producer. However, studies evaluating the genotype x environment (G x E) interactions in cotton are scarce in this country. Therefore, the goal of this study was to evaluate the G x E interactions in two important traits in cotton (fiber yield and fiber length) using the method proposed by Eberhart and Russell (simple linear regression) and reaction norm models (random regression). Eight trials with sixteen upland cotton genotypes, conducted in a randomized block design, were used. It was possible to identify a genotype with wide adaptability and stability for both traits. Reaction norm models have excellent theoretical and practical properties and led to more informative and accurate results than the method proposed by Eberhart and Russell and should, therefore, be preferred. Curves of genotypic values as a function of the environmental gradient, which predict the behavior of the genotypes along the environmental gradient, were generated. These curves make possible the recommendation to untested environmental levels.

Cluster Tails for Critical Power-Law Inhomogeneous Random Graphs

NASA Astrophysics Data System (ADS)

van der Hofstad, Remco; Kliem, Sandra; van Leeuwaarden, Johan S. H.

2018-04-01

Recently, the scaling limit of cluster sizes for critical inhomogeneous random graphs of rank-1 type having finite variance but infinite third moment degrees was obtained in Bhamidi et al. (Ann Probab 40:2299-2361, 2012). It was proved that when the degrees obey a power law with exponent τ \\in (3,4), the sequence of clusters ordered in decreasing size and multiplied through by n^{-(τ -2)/(τ -1)} converges as n→ ∞ to a sequence of decreasing non-degenerate random variables. Here, we study the tails of the limit of the rescaled largest cluster, i.e., the probability that the scaling limit of the largest cluster takes a large value u, as a function of u. This extends a related result of Pittel (J Combin Theory Ser B 82(2):237-269, 2001) for the Erdős-Rényi random graph to the setting of rank-1 inhomogeneous random graphs with infinite third moment degrees. We make use of delicate large deviations and weak convergence arguments.

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.

The influence of training characteristics on the effect of aerobic exercise training in patients with chronic heart failure: A meta-regression analysis.

PubMed

Vromen, T; Kraal, J J; Kuiper, J; Spee, R F; Peek, N; Kemps, H M

2016-04-01

Although aerobic exercise training has shown to be an effective treatment for chronic heart failure patients, there has been a debate about the design of training programs and which training characteristics are the strongest determinants of improvement in exercise capacity. Therefore, we performed a meta-regression analysis to determine a ranking of the individual effect of the training characteristics on the improvement in exercise capacity of an aerobic exercise training program in chronic heart failure patients. We focused on four training characteristics; session frequency, session duration, training intensity and program length, and their product; total energy expenditure. A systematic literature search was performed for randomized controlled trials comparing continuous aerobic exercise training with usual care. Seventeen unique articles were included in our analysis. Total energy expenditure appeared the only training characteristic with a significant effect on improvement in exercise capacity. However, the results were strongly dominated by one trial (HF-action trial), accounting for 90% of the total patient population and showing controversial results compared to other studies. A repeated analysis excluding the HF-action trial confirmed that the increase in exercise capacity is primarily determined by total energy expenditure, followed by session frequency, session duration and session intensity. These results suggest that the design of a training program requires high total energy expenditure as a main goal. Increases in training frequency and session duration appear to yield the largest improvement in exercise capacity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial

PubMed Central

Scriven, James E.; Rhein, Joshua; Hullsiek, Katherine Huppler; von Hohenberg, Maximilian; Linder, Grace; Rolfes, Melissa A.; Williams, Darlisha A.; Taseera, Kabanda; Meya, David B.; Meintjes, Graeme; Boulware, David R.

2015-01-01

Introduction. Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1–2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome. Methods. Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis. Results. More participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation. Conclusions. Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated. PMID:25651842

Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?

PubMed

Als-Nielsen, Bodil; Chen, Wendong; Gluud, Christian; Kjaergard, Lise L

2003-08-20

Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.

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.

Random Versus Blocked Practice to Enhance Mental Representation in Golf Putting.

PubMed

Fazeli, Davoud; Taheri, HamidReza; Saberi Kakhki, Alireza

2017-06-01

The purpose of this study was to investigate changes in mental representation from either random or blocked practice when engaged in golf putting. Thirty participants were randomly assigned to random practice, blocked practice, and no-practice groups. First, we measured novice golfers' initial mental representation levels and required them to perform 18 putting trials as a pre-test. We then asked random and blocked groups to practice in accordance with their group assignment for six consecutive days (10 blocks each day, 18 trials each). A week after the last practice session, we re-measured all participants' final mental representation levels and required them to perform 18 putting trials to evaluate learning retention through practice. While those engaged in the random practice method putted more poorly during acquisition (i.e., practice) than those in blocked practice, the random practice group experienced more accurate retention during the final putting trials, and they showed a more structured mental representation than those in blocked practice, one that was more similar to that of skilled golfers. These results support the acquisition of a rich mental representation through random versus blocked practice.

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

PubMed Central

2011-01-01

Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

New clinical trial to study long-term progression of brain and spine cancers | Center for Cancer Research

Cancer.gov

Dr. Mark Gilbert, Chief, Neuro-Oncology Branch, describes an ambitious new clinical trial that, for the first time, will study the long-term progression of brain and spine cancers. The 10,000 patient trial is the largest of its kind and will follow patients throughout the course of their disease. In addition to identifying optimal treatments for common brain and spine cancers,

Structured-light 3D scanner in use to assess the human body posture in physical therapy - a pilot study.

PubMed

Kurzydło, Wojciech; Stach, Beata; Bober, Aleksandra; Wodzińska, Mariola; Długosz, Mirosława M

2014-01-01

The main goal of this study was to asses the possibility of using mass production structured-light 3d scanner to asses human body posture. The study was conducted on a healthy 23 year old volunteer and a lay-figure. The experiment consisted of 28 3D scans, divided into three separate tests. The largest deviation observed in the first two trials was 24.42 mm. While the largest deviation observed in the third trial was 49.91 mm. Data obtained with the mass production structured-light 3d scanner may have comparable or better performance than commercially available systems for the assessment of BP.

When Is It Possible to Conduct a Randomized Controlled Trial in Education at Reduced Cost, Using Existing Data Sources? A Brief Overview

ERIC Educational Resources Information Center

Coalition for Evidence-Based Policy, 2007

2007-01-01

The purpose of this Guide is to advise researchers, policymakers, and others on when it is possible to conduct a high-quality randomized controlled trial in education at reduced cost. Well-designed randomized controlled trials are recognized as the gold standard for evaluating the effectiveness of an intervention (i.e., program or practice) in…

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

[Clinical trial on the effectiveness and safety of triptorelin in treatment of uterine leiomyoma].

PubMed

Zhou, Ying-fang; Yang, Dong-zi; Hu, Li-na; Zheng, Shu-rong

2005-07-01

To evaluate the effectiveness and safety of triptorelin in the treatment of uterine leiomyoma. A multi-center, prospective, randomly controlled clinical trial was carried out from Dec. 2002 to Mar. 2004 in three university hospitals. A total of 125 qualified patients with uterine leiomyoma were randomly divided into either triptorelin group (63 cases) treated with 3.75 mg triptorelin injected intramuscularly or leuprorelin group (62 cases) treated with 3.75 mg leuprorelin injected subcutaneously. Both drugs were injected every 28 days for a total of 3 months. All 125 patients finished the trial. The uterine volumes were similar before treatment between the triptorelin group and the leuprorelin group and were decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 51% and 49%, respectively, without significant difference between two groups (P > 0.05). The volumes of the largest leiomyoma decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 50% and 48% in the triptorelin and leuprorelin groups, respectively, without significant difference between them (P > 0.05). Patients with serum level of 17beta-estradiol < 183 pmol/L accounted for 94% in both groups. The hemoglobin and serum ferrum levels were both significantly increased in the two groups after treatment (P < 0.05). The amenorrhea rates after 3 months of treatment were 97% in the triptorelin group and 95% in the leuprorelin group (P > 0.05). Dysmenorrhea, noncyclic pelvic pain and pressure-like symptoms were relieved quickly and remarkably in both groups after treatment. The rates of adverse event occurred in 71% of patients in both groups. The main side effects included flare-up effects and hypoestrogenic symptoms. Nine patients in the triptorelin group and 6 in the leuprorelin group received add-back therapy with tibolone 1.25-2.50 mg/d because of remarkable climacteric-like symptoms. Treatment of uterine leiomyoma with triptorelin for 3 months is both effective and safe in Chinese women.

International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol.

PubMed

Williams, Leanne M; Rush, A John; Koslow, Stephen H; Wisniewski, Stephen R; Cooper, Nicholas J; Nemeroff, Charles B; Schatzberg, Alan F; Gordon, Evian

2011-01-05

Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1

Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors

PubMed Central

Colditz, Graham A.; Rock, Cheryl L.; Sedjo, Rebecca L.; Liu, Jingxia; Wolin, Kathleen Y.; Krontiras, Helen; Byers, Tim; Pakiz, Bilgé; Parker, Barbara A.; Naughton, Michael; Elias, Anthony; Ganz, Patricia A.

2015-01-01

Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % (p < 0.0001) and 3.7 versus 1.3 % (p<0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25–45 kg/m2) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, −3.45 (95 % Confidence Interval [CI] −6.10, –0.79, p = 0.0109) and 0.10 (95 %CI 0.04, 0.16, p = 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm −2.72 (95 % CI −5.45, 0.01, p = 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, −1.64 (95 % CI −3.13, –0.15, p = 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time. PMID:26518022

Photoaging smartphone app promoting poster campaign to reduce smoking prevalence in secondary schools: the Smokerface Randomized Trial: design and baseline characteristics

PubMed Central

Holzapfel, Julia; Baudson, Tanja G; Sies, Katharina; Jakob, Lena; Baumert, Hannah Maria; Heckl, Marlene; Cirac, Ana; Suhre, Janina L; Mathes, Verena; Spielmann, Hannah; Rigotti, Nancy; Herth, Felix; Groneberg, David A; Raupach, Tobias; Gall, Henning; Bauer, Claudia; Marek, Pat; Batra, Anil; Harrison, Chase H; Taha, Lava; Owczarek, Andreas; Hofmann, Felix J; Thomas, Roger; Mons, Ute; Kreuter, Michael

2016-01-01

Introduction Smoking is the largest cause of preventable death globally. Most smokers smoke their first cigarette in early adolescence. We took advantage of the widespread availability of mobile phones and adolescents’ interest in appearance to develop a free photoaging app which is promoted via a poster campaign in secondary schools. This study aims to evaluate its effectiveness regarding smoking prevalence and students’ attitudes towards smoking. Methods and analysis A randomised controlled trial is conducted with 9851 students of both genders with an average age of 12 years in grades 6 and 7 of 126 secondary schools in Germany. At present, cigarette smoking prevalence in our sample is 4.7%, with 4.6% of the students currently using e-cigarettes (1.6% use both). The prospective experimental study design includes measurements at baseline and at 6, 12 and 24 months postintervention via a questionnaire plus a random cotinine saliva sample at 24 months postintervention. The study groups consist of randomised schools receiving the Smokerface poster campaign and control schools with comparable baseline data (no intervention). The primary end point is the difference of change in smoking prevalence in the intervention group versus the difference in the control group at 24 months follow-up. Longitudinal changes in smoking-related attitudes, the number of new smokers and quitters and the change in the number of never-smokers will be compared between the two groups as secondary outcomes. Ethics and dissemination Ethical approval was obtained from the ethics committee of the University of Gießen and the ministries of cultural affairs, both in Germany. Results will be disseminated at conferences, in peer-reviewed journals, on our websites and throughout the multinational Education Against Tobacco network. Trial registration number NCT02544360, Pre-results. PMID:27821601

Finite-sample corrected generalized estimating equation of population average treatment effects in stepped wedge cluster randomized trials.

PubMed

Scott, JoAnna M; deCamp, Allan; Juraska, Michal; Fay, Michael P; Gilbert, Peter B

2017-04-01

Stepped wedge designs are increasingly commonplace and advantageous for cluster randomized trials when it is both unethical to assign placebo, and it is logistically difficult to allocate an intervention simultaneously to many clusters. We study marginal mean models fit with generalized estimating equations for assessing treatment effectiveness in stepped wedge cluster randomized trials. This approach has advantages over the more commonly used mixed models that (1) the population-average parameters have an important interpretation for public health applications and (2) they avoid untestable assumptions on latent variable distributions and avoid parametric assumptions about error distributions, therefore, providing more robust evidence on treatment effects. However, cluster randomized trials typically have a small number of clusters, rendering the standard generalized estimating equation sandwich variance estimator biased and highly variable and hence yielding incorrect inferences. We study the usual asymptotic generalized estimating equation inferences (i.e., using sandwich variance estimators and asymptotic normality) and four small-sample corrections to generalized estimating equation for stepped wedge cluster randomized trials and for parallel cluster randomized trials as a comparison. We show by simulation that the small-sample corrections provide improvement, with one correction appearing to provide at least nominal coverage even with only 10 clusters per group. These results demonstrate the viability of the marginal mean approach for both stepped wedge and parallel cluster randomized trials. We also study the comparative performance of the corrected methods for stepped wedge and parallel designs, and describe how the methods can accommodate interval censoring of individual failure times and incorporate semiparametric efficient estimators.

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 130,000 records retrieved by this term were reports of trials. The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as randomized trials in MEDLINE, 959 (5%) were in languages other than English. The EMBASE search identified an additional 658 reports in languages other than English, of which the highest number were in Chinese (320). Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE, especially in some languages other than English. The search strategy used was subjectively derived from a small 'gold standard' set of test records and was not validated in an independent test set. We intend to design an objectively-derived validated search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of randomized trials identified compared with the frequency of these terms across the entire EMBASE database. PMID:18826567

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

PubMed Central

2014-01-01

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

A Multivariate Randomization Text of Association Applied to Cognitive Test Results

NASA Technical Reports Server (NTRS)

Ahumada, Albert; Beard, Bettina

2009-01-01

Randomization tests provide a conceptually simple, distribution-free way to implement significance testing. We have applied this method to the problem of evaluating the significance of the association among a number (k) of variables. The randomization method was the random re-ordering of k-1 of the variables. The criterion variable was the value of the largest eigenvalue of the correlation matrix.

Individual or group antenatal education for childbirth or parenthood, or both.

PubMed

Gagnon, A J; Sandall, J

2007-07-18

Structured antenatal education programs for childbirth or parenthood, or both, are commonly recommended for pregnant women and their partners by healthcare professionals in many parts of the world. Such programs are usually offered to groups but may be offered to individuals. To assess the effects of this education on knowledge acquisition, anxiety, sense of control, pain, labour and birth support, breastfeeding, infant-care abilities, and psychological and social adjustment. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2006), CINAHL (1982 to April 2006), ERIC (1984 to April 2006), EMBASE (1980 to April 2006) and PsycINFO (1988 to April 2006). We handsearched the Journal of Psychosomatic Research from 1956 to April 2006 and reviewed the reference lists of retrieved studies. Randomized controlled trials of any structured educational program provided during pregnancy by an educator to either parent that included information related to pregnancy, birth or parenthood. The educational interventions could have been provided on an individual or group basis. Educational interventions directed exclusively to either increasing breastfeeding success, knowledge of and coping skills concerning postpartum depression, improving maternal psycho-social health including anxiety, depression and self-esteem or reducing smoking were excluded. Both authors assessed trial quality and extracted data from published reports. Nine trials, involving 2284 women, were included. Thirty-seven studies were excluded. Educational interventions were the focus of eight of the studies (combined n = 1009). Details of the randomization procedure, allocation concealment, and/or participant accrual or loss for these trials were not reported. No consistent results were found. Sample sizes were very small to moderate, ranging from 10 to 318. No data were reported concerning anxiety, breastfeeding success, or general social support. Knowledge acquisition, sense of control, factors related to infant-care competencies, and some labour and birth outcomes were measured. The largest of the included studies (n = 1275) examined an educational and social support intervention to increase vaginal birth after caesarean section. This high-quality study showed similar rates of vaginal birth after caesarean section in 'verbal' and 'document' groups (relative risk 1.08, 95% confidence interval 0.97 to 1.21). The effects of general antenatal education for childbirth or parenthood, or both, remain largely unknown. Individualized prenatal education directed toward avoidance of a repeat caesarean birth does not increase the rate of vaginal birth after caesarean section.

Assessment of the Reporting Quality of Placebo-controlled Randomized Trials on the Treatment of Type 2 Diabetes With Traditional Chinese Medicine in Mainland China: A PRISMA-Compliant Systematic Review.

PubMed

Zhao, Xiyan; Zhen, Zhong; Guo, Jing; Zhao, Tianyu; Ye, Ru; Guo, Yu; Chen, Hongdong; Lian, Fengmei; Tong, Xiaolin

2016-01-01

Placebo-controlled randomized trials are often used to evaluate the absolute effect of new treatments and are considered gold standard for clinical trials. No studies, however, have yet been conducted evaluating the reporting quality of placebo-controlled randomized trials. The current study aims to assess the reporting quality of placebo-controlled randomized trials on treatment of diabetes with Traditional Chinese Medicine (TCM) in Mainland China and to provide recommendations for improvements.China National Knowledge Infrastructure database, Wanfang database, China Biology Medicine database, and VIP database were searched for placebo-controlled randomized trials on treatment of diabetes with TCM. Review, animal experiment, and randomized controlled trials without placebo control were excluded. According to Consolidated Standards of Reporting Trials (CONSORT) 2010 checklists items, each item was given a yes or no depending on whether it was reported or not.A total of 68 articles were included. The reporting percentage in each article ranged from 24.3% to 73%, and 30.9% articles reported more than 50% of the items. Seven of the 37 items were reported more than 90% of the items, whereas 7 items were not mentioned at all. The average reporting for "title and abstract," "introduction," "methods," "results," "discussion," and "other information" was 43.4%, 78.7%, 40.1%, 49.9%, 71.1%, and 17.2%, respectively. The percentage of each section had increased after 2010. In addition, the reporting of multiple study centers, funding, placebo species, informed consent forms, and ethical approvals were 14.7%, 50%, 36.85%, 33.8%, and 4.4%, respectively.Although a scoring system was created according to the CONSORT 2010 checklist, it was not designed as an assessment tool. According to CONSORT 2010, the reporting quality of placebo-controlled randomized trials on the treatment of diabetes with TCM improved after 2010. Future improvements, however, are still needed, particularly in methods sections.

A generic minimization random allocation and blinding system on web.

PubMed

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

2006-12-01

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

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…

The influence of an uncertain force environment on reshaping trial-to-trial motor variability.

PubMed

Izawa, Jun; Yoshioka, Toshinori; Osu, Rieko

2014-09-10

Motor memory is updated to generate ideal movements in a novel environment. When the environment changes every trial randomly, how does the brain incorporate this uncertainty into motor memory? To investigate how the brain adapts to an uncertain environment, we considered a reach adaptation protocol where individuals practiced moving in a force field where a noise was injected. After they had adapted, we measured the trial-to-trial variability in the temporal profiles of the produced hand force. We found that the motor variability was significantly magnified by the adaptation to the random force field. Temporal profiles of the motor variance were significantly dissociable between two different types of random force fields experienced. A model-based analysis suggests that the variability is generated by noise in the gains of the internal model. It further suggests that the trial-to-trial motor variability magnified by the adaptation in a random force field is generated by the uncertainty of the internal model formed in the brain as a result of the adaptation.

Introduction to the Special Issue.

ERIC Educational Resources Information Center

Petrosino, Anthony

2003-01-01

Introduces the articles of this special issue focusing on randomized field trials in criminology. In spite of the overall lack of randomized field trials in criminology, some agencies and individuals are able to mount an impressive number of field trials, and these articles focus on their experiences. (SLD)

Latent Subgroup Analysis of a Randomized Clinical Trial Through a Semiparametric Accelerated Failure Time Mixture Model

PubMed Central

Altstein, L.; Li, G.

2012-01-01

Summary This paper studies a semiparametric accelerated failure time mixture model for estimation of a biological treatment effect on a latent subgroup of interest with a time-to-event outcome in randomized clinical trials. Latency is induced because membership is observable in one arm of the trial and unidentified in the other. This method is useful in randomized clinical trials with all-or-none noncompliance when patients in the control arm have no access to active treatment and in, for example, oncology trials when a biopsy used to identify the latent subgroup is performed only on subjects randomized to active treatment. We derive a computational method to estimate model parameters by iterating between an expectation step and a weighted Buckley-James optimization step. The bootstrap method is used for variance estimation, and the performance of our method is corroborated in simulation. We illustrate our method through an analysis of a multicenter selective lymphadenectomy trial for melanoma. PMID:23383608

The efficacy of anticonvulsants on orofacial pain: a systematic review.

PubMed

Martin, Wilhelmus J J M; Forouzanfar, Tymour

2011-05-01

Controversy exists about the effectiveness of anticonvulsants for the management of orofacial pain disorders. To ascertain appropriate therapies, a systematic review was conducted of existing randomized controlled trials. Trials were identified from PubMed, Cochrane, and Ovid Medline databases from 1962 through March 2010, from references in retrieved reports, and from references in review articles. Eight useful trials were identified for this review. Six studies were randomized placebo-controlled trials and 2 studies were randomized active-controlled. Two independent investigators reviewed these articles by using a 15-item checklist. Four studies were classified as "high quality." However, heterogeneity of the trials and the small sample sizes precluded the drawing of firm conclusions about the efficacy of the interventions studied on orofacial pain patients. There is limited to moderate evidence supporting the efficacy of commonly used anticonvulsants for treatment of patients with orofacial pain disorders. More randomized controlled trials are needed on the efficacy of anticonvulsants. Copyright © 2011 Mosby, Inc. All rights reserved.

Some practical problems in implementing randomization.

PubMed

Downs, Matt; Tucker, Kathryn; Christ-Schmidt, Heidi; Wittes, Janet

2010-06-01

While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice. At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method. We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling. Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur. Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235-245. http://ctj.sagepub.com.

Prophylactic sildenafil citrate improves select aspects of sexual function in men treated with radiotherapy for prostate cancer.

PubMed

Zelefsky, Michael J; Shasha, Daniel; Branco, Rebekah Dunn; Kollmeier, Marisa; Baser, Raymond E; Pei, Xin; Ennis, Ronald; Stock, Richard; Bar-Chama, Natan; Mulhall, John P

2014-09-01

We studied adjuvant daily sildenafil citrate during and after radiotherapy for prostate cancer for erectile function preservation. We performed a randomized, prospective trial of 279 patients with localized prostate cancer treated with radiotherapy who received sildenafil citrate (50 mg daily) or placebo (2:1 randomization). Medication/placebo was initiated 3 days before treatment and continued daily for 6 months. Before therapy and 3, 6, 9, 12, 18 and 24 months after radiotherapy patients completed the IIEF questionnaire, including the erectile function domain, the I-PSS questionnaire and the RAND SF-36®. All IIEF domains were scored. At 12 months erectile function scores were better for sildenafil citrate than placebo (p = 0.018), 73% of patients on sildenafil citrate vs 50% on placebo had mild/no erectile dysfunction (p = 0.024) and the sildenafil citrate arm had superior overall satisfaction (p = 0.027) and IIEF total scores (p = 0.043). At 24 months erectile function and IIEF scores were no longer significantly better for sildenafil citrate (p = 0.172 and 0.09, respectively) and yet overall satisfaction scores were higher (p = 0.033). Sexual desire scores in patients who received sildenafil citrate were higher at 24 months although they had completed drug therapy 18 months previously (p = 0.049). At 24 months 81.6% of patients on sildenafil citrate and 56.0% of those on placebo achieved functional erection with or without erectile dysfunction medication (p = 0.045). Daily sildenafil citrate during and after radiotherapy for prostate cancer was associated with improved overall sexual function compared with placebo for various sexual function domains. To our knowledge this is the largest randomized, prospective, controlled trial to show the usefulness of a phosphodiesterase-5 inhibitor as a rehabilitation strategy in patients with prostate cancer who received radiation therapy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial☆,☆☆

PubMed Central

Mangano, Kelsey M.; Hutchins-Wiese, Heather L.; Kenny, Anne M.; Walsh, Stephen J.; Abourizk, Robin H.; Bruno, Richard S.; Lipcius, Rosanne; Fall, Pamela; Kleppinger, Alison; Kenyon-Pesce, Lisa; Prestwood, Karen M.; Kerstetter, Jane E.

2015-01-01

Soy foods contain several components, notably, isoflavones and amino acids, that may improve cardiovascular health. We evaluated the long-term effect of soy protein and/or soy isoflavones supplementation on serum lipids and inflammatory markers using a 1-year randomized, double-blind, placebo-control, clinical trial in 131 healthy ambulatory women older than 60 years. We hypothesized that soy protein, in combination with isoflavones, would have the largest positive effect on coronary heart disease risk factors (serum lipids and inflammatory markers) compared with either intervention alone and that, within groups receiving isoflavones, equol producers would have more positive effects on coronary heart disease risk factors than nonequol producers. After a 1-month baseline period, participants were randomized into 1 of 4 intervention groups: soy protein (18 g/d) and isoflavone tablets (105 mg/d isoflavone aglycone equivalents), soy protein and placebo tablets, control protein and isoflavone tablets, or control protein and placebo tablets. T Tests were used to assess differences between equol and nonequol producers. Ninety-seven women completed the trial. Consumption of protein powder and isoflavone tablets did not differ among groups, and compliance with study powder and tablets was 79% and 90%, respectively. After 1 year, in the entire population, there were either no or little effects on serum lipids and inflammatory markers, regardless of treatment group. Equol producers, when analyzed separately, had significant improvements in total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios (−5.9%, P = .02; −7.2%, P = .04 respectively). Soy protein and isoflavone (either alone or together) did not impact serum lipids or inflammatory markers. Therefore, they should not be considered an effective intervention to prevent cardiovascular disease because of lipid modification in healthy late postmenopausal women lacking the ability to produce equol. PMID:24267042

Efficacy and safety of once-daily insulin degludec/insulin aspart compared with once-daily insulin glargine in participants with Type 2 diabetes: a randomized, treat-to-target study.

PubMed

Kumar, S; Jang, H C; Demirağ, N G; Skjøth, T V; Endahl, L; Bode, B

2017-02-01

To investigate, in a 26-week, open-label, randomized, treat-to-target trial, the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily vs insulin glargine (IGlar) once daily in adults with Type 2 diabetes, inadequately controlled on basal insulin. Participants were randomized (1:1) to IDegAsp once daily or IGlar once daily in combination with existing oral antidiabetic drugs. IDegAsp once daily was administered with the main evening meal or the largest meal of the day (agreed at baseline); dosing time was maintained throughout the trial. Participants titrated their insulin dose weekly to a mean pre-breakfast self-measured plasma glucose target [3.9-4.9 mmol/l (70-89 mg/dl)]. IDegAsp once daily was non-inferior to IGlar once daily in reducing HbA 1c after 26 weeks [mean estimated treatment difference IDegAsp once daily - IGlar once daily: -0.03% (95% CI -0.20, 0.14)]. The evening meal glucose increment was significantly lower with IDegAsp once daily vs IGlar once daily [estimated treatment difference IDegAsp once daily - IGlar once daily: -1.32 mmol/l (95% CI -1.93, -0.72); P < 0.05]. The overall confirmed hypoglycaemia rate was higher with IDegAsp once daily (estimated rate ratio 1.43; 95% CI 1.07, 1.92; P < 0.05). The rate of nocturnal hypoglycaemia did not significantly differ between the IDegAsp and IGlar groups [estimated rate ratio 0.80 (95% CI 0.49, 1.30); not significant]. In participants with Type 2 diabetes inadequately controlled on basal insulin, IDegAsp once daily improved glycaemic control and was non-inferior to IGlar once daily. IDegAsp led to higher rates of overall hypoglycaemia than IGlar, with no significant difference in rates of nocturnal hypoglycaemia. © 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

PubMed

Quyyumi, Arshed A; Vasquez, Alejandro; Kereiakes, Dean J; Klapholz, Marc; Schaer, Gary L; Abdel-Latif, Ahmed; Frohwein, Stephen; Henry, Timothy D; Schatz, Richard A; Dib, Nabil; Toma, Catalin; Davidson, Charles J; Barsness, Gregory W; Shavelle, David M; Cohen, Martin; Poole, Joseph; Moss, Thomas; Hyde, Pamela; Kanakaraj, Anna Maria; Druker, Vitaly; Chung, Amy; Junge, Candice; Preti, Robert A; Smith, Robin L; Mazzo, David J; Pecora, Andrew; Losordo, Douglas W

2017-01-20

Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364. © 2016 American Heart Association, Inc.

Randomized controlled trial to determine the effectiveness of an interactive multimedia food safety education program for clients of the special supplemental nutrition program for women, infants, and children.

PubMed

Trepka, Mary Jo; Newman, Frederick L; Davila, Evelyn P; Matthew, Karen J; Dixon, Zisca; Huffman, Fatma G

2008-06-01

Pregnant women and the very young are among those most susceptible to foodborne infections and at high risk of a severe outcome from foodborne infections. To determine if interactive multimedia is a more effective method than pamphlets for delivering food safety education to Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clients. A randomized controlled trial of WIC clients was conducted. Self-reported food safety practices were compared between pre- and postintervention questionnaires completed >or=2 months after the intervention. Pregnant WIC clients or female caregivers (usually mothers) of WIC clients who were 18 years of age or older and able to speak and read English were recruited from an inner-city WIC clinic. Participants were randomized to receive food safety pamphlets or complete an interactive multimedia food safety education program on a computer kiosk. Change from pre- to postintervention food safety scores. A mean food safety score was determined for each participant for the pre- and postintervention questionnaires. The scores were used in a two-group repeated measures analysis of variance. Of the 394 participants, 255 (64.7%) completed the postintervention questionnaire. Satisfaction with the program was high especially among those with no education beyond high school. When considering a repeated measures analysis of variance model with the two fixed between-subject effects of group and age, a larger improvement in score in the interactive multimedia group than in the pamphlet group (P=0.005) was found, but the size of the group effect was small (partial eta(2)=0.033). Women aged 35 years or older in the interactive multimedia group had the largest increase in score. The interactive multimedia was well-accepted and resulted in improved self-reported food safety practices, suggesting that interactive multimedia is an effective option for food safety education in WIC clinics.

Presentation of Diagnostic Information to Doctors May Change Their Interpretation and Clinical Management: A Web-Based Randomised Controlled Trial.

PubMed

Ben-Shlomo, Yoav; Collin, Simon M; Quekett, James; Sterne, Jonathan A C; Whiting, Penny

2015-01-01

There is little evidence on how best to present diagnostic information to doctors and whether this makes any difference to clinical management. We undertook a randomised controlled trial to see if different data presentations altered clinicians' decision to further investigate or treat a patient with a fictitious disorder ("Green syndrome") and their ability to determine post-test probability. We recruited doctors registered with the United Kingdom's largest online network for medical doctors between 10 July and 6" November 2012. Participants were randomised to one of four arms: (a) text summary of sensitivity and specificity, (b) Fagan's nomogram, (c) probability-modifying plot (PMP), (d) natural frequency tree (NFT). The main outcome measure was the decision whether to treat, not treat or undertake a brain biopsy on the hypothetical patient and the correct post-test probability. Secondary outcome measures included knowledge of diagnostic tests. 917 participants attempted the survey and complete data were available from 874 (95.3%). Doctors randomized to the PMP and NFT arms were more likely to treat the patient than those randomized to the text-only arm. (ORs 1.49, 95% CI 1.02, 2.16) and 1.43, 95% CI 0.98, 2.08 respectively). More patients randomized to the PMP (87/218-39.9%) and NFT (73/207-35.3%) arms than the nomogram (50/194-25.8%) or text only (30/255-11.8%) arms reported the correct post-test probability (p <0.001). Younger age, postgraduate training and higher self-rated confidence all predicted better knowledge performance. Doctors with better knowledge were more likely to view an optional learning tutorial (OR per correct answer 1.18, 95% CI 1.06, 1.31). Presenting diagnostic data using a probability-modifying plot or natural frequency tree influences the threshold for treatment and improves interpretation of tests results compared to text summary of sensitivity and specificity or Fagan's nomogram.

[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. At the same time, in order to improve the reporting quality of randomized controlled trials, CONSORT standards should be adopted in the preparation of research reports and submissions. Copyright© by the Chinese Pharmaceutical Association.

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494

PubMed Central

2012-01-01

Background Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study. Methods/Design The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up. Discussion At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program. Trial registration German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494 PMID:22394693

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.

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

Online Early Resilience Intervention for Combat-Related PTSD in Military Primary Healthcare Settings: A Randomized Trial of DESTRESS-PC

DTIC Science & Technology

2009-08-01

Bryant, R, Engel, CC (2004). A therapist-assisted internet self-help program for traumatic stress . Professional Psychology: Research and Practice, 35...Combat-Related PTSD in Military Primary Healthcare Settings: A Randomized Trial of “DESTRESS-PC” PRINCIPAL INVESTIGATOR: Charles Engel...Early Resilience Intervention for Combat-Related PTSD in Military Primary Healthcare Settings: A Randomized Trial of DESTRESS-PC 5b. GRANT NUMBER

Evaluation of internal peer-review to train nurses recruiting to a randomized controlled trial--Internal Peer-review for Recruitment Training in Trials (InterPReTiT).

PubMed

Mann, Cindy; Delgado, Debbie; Horwood, Jeremy

2014-04-01

A discussion and qualitative evaluation of the use of peer-review to train nurses and optimize recruitment practice in a randomized controlled trial. Sound recruitment processes are critical to the success of randomized controlled trials. Nurses recruiting to trials must obtain consent for an intervention that is administered for reasons other than anticipated benefit to the patient. This requires not only patients' acquiescence but also evidence that they have weighed the relevant information in reaching their decision. How trial information is explained is vital, but communication and training can be inadequate. A discussion of a new process to train nurses recruiting to a randomized controlled trial. Literature from 1999-2013 about consenting to trials is included. Over 3 months from 2009-2010, recruiting nurses reviewed recruitment interviews recorded during the pilot phase of a single-site randomized controlled trial and noted content, communication style and interactions. They discussed their findings during peer-review meetings, which were audio-recorded and analysed using qualitative methodology. Peer-review can enhance nurses' training in trial recruitment procedures by supporting development of the necessary communication skills, facilitating consistency in information provision and sharing best practice. Nurse-led peer-review can provide a forum to share communication strategies that will elicit and address participant concerns and obtain evidence of participant understanding prior to consent. Comparing practice can improve consistency and accuracy of trial information and facilitate identification of recruitment issues. Internal peer-review was well accepted and promoted team cohesion. Further evaluation is needed. © 2013 John Wiley & Sons Ltd.

Study protocol for two randomized controlled trials examining the effectiveness and safety of current weekend allied health services and a new stakeholder-driven model for acute medical/surgical patients versus no weekend allied health services.

PubMed

Haines, Terry P; O'Brien, Lisa; Mitchell, Deb; Bowles, Kelly-Ann; Haas, Romi; Markham, Donna; Plumb, Samantha; Chiu, Timothy; May, Kerry; Philip, Kathleen; Lescai, David; McDermott, Fiona; Sarkies, Mitchell; Ghaly, Marcelle; Shaw, Leonie; Juj, Genevieve; Skinner, Elizabeth H

2015-04-02

Disinvestment from inefficient or ineffective health services is a growing priority for health care systems. Provision of allied health services over the weekend is now commonplace despite a relative paucity of evidence supporting their provision. The relatively high cost of providing this service combined with the paucity of evidence supporting its provision makes this a potential candidate for disinvestment so that resources consumed can be used in other areas. This study aims to determine the effectiveness, cost-effectiveness and safety of the current model of weekend allied health service and a new stakeholder-driven model of weekend allied health service delivery on acute medical and surgical wards compared to having no weekend allied health service. Two stepped wedge, cluster randomised trials of weekend allied health services will be conducted in six acute medical/surgical wards across two public metropolitan hospitals in Melbourne (Australia). Wards have been chosen to participate by management teams at each hospital. The allied health services to be investigated will include physiotherapy, occupational therapy, speech therapy, dietetics, social work and allied health assistants. At baseline, all wards will be receiving weekend allied health services. Study 1 intervention will be the sequential disinvestment (roll-in) of the current weekend allied health service model from each participating ward in monthly intervals and study 2 will be the roll-out of a new stakeholder-driven model of weekend allied health service delivery. The order in which weekend allied health services will be rolled in and out amongst participating wards will be determined randomly. This trial will be conducted in each of the two participating hospitals at a different time interval. Primary outcomes will be length of stay, rate of unplanned hospital readmission within 28 days and rate of adverse events. Secondary outcomes will be number of complaints and compliments, staff absenteeism, and patient discharge destination, satisfaction, and functional independence at discharge. This is the world's first application of the recently described non-inferiority (roll-in) stepped wedge trial design, and the largest investigation of the effectiveness of weekend allied health services on acute medical surgical wards to date. Australian New Zealand Clinical Trials Registry. ACTRN12613001231730 (first study) and ACTRN12613001361796 (second study). Was this trial prospectively registered?: Yes. Date registered: 8 November 2013 (first study), 12 December 2013 (second study). Anticipated completion: June 2015. Protocol version: 1. Role of trial sponsor: KP and DL are directly employed by one of the trial sponsors, their roles were: KP assisted with overall development of research design and assisted with overall project management; DL contributed to project management, administration and communications strategy.

Experiences of being a control group: lessons from a UK-based randomized controlled trial of group singing as a health promotion initiative for older people.

PubMed

Skingley, Ann; Bungay, Hilary; Clift, Stephen; Warden, June

2014-12-01

Existing randomized controlled trials within the health field suggest that the concept of randomization is not always well understood and that feelings of disappointment may occur when participants are not placed in their preferred arm. This may affect a study's rigour and ethical integrity if not addressed. We aimed to test whether these issues apply to a healthy volunteer sample within a health promotion trial of singing for older people. Written comments from control group participants at two points during the trial were analysed, together with individual semi-structured interviews with a small sample (n = 11) of this group. We found that motivation to participate in the trial was largely due to the appeal of singing and disappointment resulted from allocation to the control group. Understanding of randomization was generally good and feelings of disappointment lessened over time and with a post-research opportunity to sing. Findings suggest that measures should be put in place to minimize the potential negative impacts of randomized controlled trials in health promotion research. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Efficient design of clinical trials and epidemiological research: is it possible?

PubMed

Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

2017-08-01

Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

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

Feasibility of a randomized single-blind crossover trial to assess the effects of the second-generation slow-release dopamine agonists pramipexole and ropinirole on cued recall memory in idiopathic mild or moderate Parkinson's disease without cognitive impairment.

PubMed

Shepherd, Thomas A; Edelstyn, Nicola M J; Longshaw, Laura; Sim, Julius; Watts, Keira; Mayes, Andrew R; Murray, Michael; Ellis, Simon J

2018-01-01

The aim was to assess the feasibility of a single-centre, single-blind, randomized, crossover design to explore the effects of two slow-release dopamine agonists, ropinirole and pramipexole, on cued recall in Parkinson's disease. As the design required a switch from the prescribed agonist (pramipexole-to-ropinirole, or ropinirole-to-pramipexole), the primary objectives were to (a) examine the efficacy of processes and procedures used to manage symptoms during the washout period and (b) to use cued recall estimates to inform a power calculation for a definitive trial. Secondary objectives were to assess consent and missing data rates, acceptability of clinical support for the OFF sessions, experience of the OFF sessions and of agonist switching, barriers-to-participation for patients and informal caregivers. Patients were randomized in a 1:1 ratio to two treatment arms and stabilized on each agonist for 6 weeks. The arms differed only in the sequence in which the agonists were administered. Cued recall was assessed ON medication and, following a washout period resulting in 93.75% agonist elimination, OFF medication. A total of 220 patients were screened: 145 were excluded and 75 invitations to participate were sent to eligible patients. Fifty-three patients declined, 22 consented and 16 completed the study. There were no serious adverse events, and rates of non-serious adverse events were equivalent between the agonists. Using the largest standard deviation (SD) of the ON-OFF difference cued recall score (inflated by ~25% to give a conservative estimate of the SD in a definitive trial) and assuming an effect of at least 10% of the observed range of OFF medication cued recall scores for either agonist to be clinically important, a main trial requires a sample size of just under 150 patients. The consent and missing data rates were 29 and 27% respectively. The washout period and the preparation for the OFF sessions were acceptable, and the sessions were manageable. The experience of switching was also manageable. Barriers to participation included concerns about disease stability, side effects, research process, carer workload and accessibility of the information sheet. This study presented challenges to recruitment both in design and execution, and while it was a major aim of the study to assess this, evaluation of these challenges provided the opportunity to explore how they could be overcome for future studies. EudraCT 2012-000801-64.

Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa.

PubMed

Keenan, Jeremy D; Bailey, Robin L; West, Sheila K; Arzika, Ahmed M; Hart, John; Weaver, Jerusha; Kalua, Khumbo; Mrango, Zakayo; Ray, Kathryn J; Cook, Catherine; Lebas, Elodie; O'Brien, Kieran S; Emerson, Paul M; Porco, Travis C; Lietman, Thomas M

2018-04-26

We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations. In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses. A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing. Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

Efficacy of Laparoscopic Nissen Fundoplication vs Transoral Incisionless Fundoplication or Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease: A Systematic Review and Network Meta-analysis.

PubMed

Richter, Joel E; Kumar, Ambuj; Lipka, Seth; Miladinovic, Branko; Velanovich, Vic

2018-04-01

The effects of transoral incisionless fundoplication (TIF) and laparoscopic Nissen fundoplication (LNF) have been compared with those of proton pump inhibitors (PPIs) or a sham procedure in patients with gastroesophageal reflux disease (GERD), but there has been no direct comparison of TIF vs LNF. We performed a systematic review and network meta-analysis of randomized controlled trials to compare the relative efficacies of TIF vs LNF in patients with GERD. We searched publication databases and conference abstracts through May 10, 2017 for randomized controlled trials that compared the efficacy of TIF or LNF with that of a sham procedure or PPIs in patients with GERD. We performed a network meta-analysis using Bayesian methods under random-effects multiple treatment comparisons. We assessed ranking probability by surface under the cumulative ranking curve. Our search identified 7 trials comprising 1128 patients. Surface under the cumulative ranking curve ranking indicated TIF had highest probability of increasing patients' health-related quality of life (0.96), followed by LNF (0.66), a sham procedure (0.35), and PPIs (0.042). LNF had the highest probability of increasing percent time at pH <4 (0.99), followed by PPIs (0.64), TIF (0.32), and the sham procedure (0.05). LNF also had the highest probability of increasing LES pressure (0.78), followed by TIF (0.72) and PPIs (0.01). Patients who underwent the sham procedure had the highest probability for persistent esophagitis (0.74), followed by those receiving TIF (0.69), LNF (0.38), and PPIs (0.19). Meta-regression showed a shorter follow-up time as a significant confounder for the outcome of health-related quality of life in studies of TIF. In a systematic review and network meta-analysis of trials of patients with GERD, we found LNF to have the greatest ability to improve physiologic parameters of GERD, including increased LES pressure and decreased percent time pH <4. Although TIF produced the largest increase in health-related quality of life, this could be due to the shorter follow-up time of patients treated with TIF vs LNF or PPIs. TIF is a minimally invasive endoscopic procedure, yet based on evaluation of benefits vs risks, we do not recommend it as a long-term alternative to PPI or LNF treatment of GERD. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

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.

Osteoporosis therapies: evidence from health-care databases and observational population studies.

PubMed

Silverman, Stuart L

2010-11-01

Osteoporosis is a well-recognized disease with severe consequences if left untreated. Randomized controlled trials are the most rigorous method for determining the efficacy and safety of therapies. Nevertheless, randomized controlled trials underrepresent the real-world patient population and are costly in both time and money. Modern technology has enabled researchers to use information gathered from large health-care or medical-claims databases to assess the practical utilization of available therapies in appropriate patients. Observational database studies lack randomization but, if carefully designed and successfully completed, can provide valuable information that complements results obtained from randomized controlled trials and extends our knowledge to real-world clinical patients. Randomized controlled trials comparing fracture outcomes among osteoporosis therapies are difficult to perform. In this regard, large observational database studies could be useful in identifying clinically important differences among therapeutic options. Database studies can also provide important information with regard to osteoporosis prevalence, health economics, and compliance and persistence with treatment. This article describes the strengths and limitations of both randomized controlled trials and observational database studies, discusses considerations for observational study design, and reviews a wealth of information generated by database studies in the field of osteoporosis.

A two-way enriched clinical trial design: combining advantages of placebo lead-in and randomized withdrawal.

PubMed

Ivanova, Anastasia; Tamura, Roy N

2015-12-01

A new clinical trial design, designated the two-way enriched design (TED), is introduced, which augments the standard randomized placebo-controlled trial with second-stage enrichment designs in placebo non-responders and drug responders. The trial is run in two stages. In the first stage, patients are randomized between drug and placebo. In the second stage, placebo non-responders are re-randomized between drug and placebo and drug responders are re-randomized between drug and placebo. All first-stage data, and second-stage data from first-stage placebo non-responders and first-stage drug responders, are utilized in the efficacy analysis. The authors developed one, two and three degrees of freedom score tests for treatment effect in the TED and give formulae for asymptotic power and for sample size computations. The authors compute the optimal allocation ratio between drug and placebo in the first stage for the TED and compare the operating characteristics of the design to the standard parallel clinical trial, placebo lead-in and randomized withdrawal designs. Two motivating examples from different disease areas are presented to illustrate the possible design considerations. © The Author(s) 2011.

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.

Designing clinical trials for amblyopia

PubMed Central

Holmes, Jonathan M.

2015-01-01

Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747

Effects of live sax music on various physiological parameters, pain level, and mood level in cancer patients: a randomized controlled trial.

PubMed

Burrai, Francesco; Micheluzzi, Valentina; Bugani, Valentina

2014-01-01

Few randomized controlled trial studies have focused on the effect of music in cancer patients, and there are no randomized controlled trials on the effects of live music with saxophone in cancer patients. To determine the effects of live saxophone music on various physiological parameters, pain level, and mood level. A randomized controlled trial study. 52 cancer patients were randomized to a control group (n = 26), an experimental group (n = 26) whose members received 30 minutes of live music therapy with saxophone. Systolic and diastolic blood pressure, pulse rate, glycemia, oxygen saturation, pain level, and mood level were measured before and after the live music performance. There was a statistical difference between the groups for oxygen saturation (0.003) and mood level (0.001). Live music performed with a saxophone could be introduced in oncology care to improve the oxygen saturation and mood in cancer patients.

A comparative study of restricted randomization procedures for multiarm trials with equal or unequal treatment allocation ratios.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr

2018-06-04

Randomization designs for multiarm clinical trials are increasingly used in practice, especially in phase II dose-ranging studies. Many new methods have been proposed in the literature; however, there is lack of systematic, head-to-head comparison of the competing designs. In this paper, we systematically investigate statistical properties of various restricted randomization procedures for multiarm trials with fixed and possibly unequal allocation ratios. The design operating characteristics include measures of allocation balance, randomness of treatment assignments, variations in the allocation ratio, and statistical characteristics such as type I error rate and power. The results from the current paper should help clinical investigators select an appropriate randomization procedure for their clinical trial. We also provide a web-based R shiny application that can be used to reproduce all results in this paper and run simulations under additional user-defined experimental scenarios. Copyright © 2018 John Wiley & Sons, Ltd.

Surgery for post-vitrectomy cataract

PubMed Central

Do, Diana V; Gichuhi, Stephen; Vedula, Satyanarayana S; Hawkins, Barbara S

2014-01-01

Background Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery. Objectives The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 May 2013. Selection criteria We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy. Data collection and analysis Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration. Main results We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery. Authors' conclusions There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined. PMID:24357418

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.

Was RA Fisher Right?

PubMed

Srivastava, Ayush; Srivastava, Anurag; Pandey, Ravindra M

2017-10-01

Randomized controlled trials have become the most respected scientific tool to measure the effectiveness of a medical therapy. The design, conduct and analysis of randomized controlled trials were developed by Sir Ronald A. Fisher, a mathematician in Great Britain. Fisher propounded that the process of randomization would equally distribute all the known and even unknown covariates in the two or more comparison groups, so that any difference observed could be ascribed to treatment effect. Today, we observe that in many situations, this prediction of Fisher does not stand true; hence, adaptive randomization schedules have been designed to adjust for major imbalance in important covariates. Present essay unravels some weaknesses inherent in Fisherian concept of randomized controlled trial.

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

Market Correlation Structure Changes Around the Great Crash: A Random Matrix Theory Analysis of the Chinese Stock Market

NASA Astrophysics Data System (ADS)

Han, Rui-Qi; Xie, Wen-Jie; Xiong, Xiong; Zhang, Wei; Zhou, Wei-Xing

The correlation structure of a stock market contains important financial contents, which may change remarkably due to the occurrence of financial crisis. We perform a comparative analysis of the Chinese stock market around the occurrence of the 2008 crisis based on the random matrix analysis of high-frequency stock returns of 1228 Chinese stocks. Both raw correlation matrix and partial correlation matrix with respect to the market index in two time periods of one year are investigated. We find that the Chinese stocks have stronger average correlation and partial correlation in 2008 than in 2007 and the average partial correlation is significantly weaker than the average correlation in each period. Accordingly, the largest eigenvalue of the correlation matrix is remarkably greater than that of the partial correlation matrix in each period. Moreover, each largest eigenvalue and its eigenvector reflect an evident market effect, while other deviating eigenvalues do not. We find no evidence that deviating eigenvalues contain industrial sectorial information. Surprisingly, the eigenvectors of the second largest eigenvalues in 2007 and of the third largest eigenvalues in 2008 are able to distinguish the stocks from the two exchanges. We also find that the component magnitudes of the some largest eigenvectors are proportional to the stocks’ capitalizations.

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…

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

DTIC Science & Technology

2017-06-01

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

Adequacy of different experimental designs for eucalyptus spacing trials in Portuguese environmental conditions

Treesearch

Paula Soares; Margarida Tome

2000-01-01

In Portugal, several eucalyptus spacing trials cover a relatively broad range of experimental designs: trials with a non-randomized block design with plots of different size and number of trees per plot; trials based on a non-systematic design in which spacings were randomized resulting in a factorial arrangement with plots of different size and shape and equal number...

CENTRAL, PEDro, PubMed, and EMBASE are the most comprehensive databases indexing randomized controlled trials of physical therapy interventions.

PubMed

Michaleff, Zoe A; Costa, Leonardo O P; Moseley, Anne M; Maher, Christopher G; Elkins, Mark R; Herbert, Robert D; Sherrington, Catherine

2011-02-01

Many bibliographic databases index research studies evaluating the effects of health care interventions. One study has concluded that the Physiotherapy Evidence Database (PEDro) has the most complete indexing of reports of randomized controlled trials of physical therapy interventions, but the design of that study may have exaggerated estimates of the completeness of indexing by PEDro. The purpose of this study was to compare the completeness of indexing of reports of randomized controlled trials of physical therapy interventions by 8 bibliographic databases. This study was an audit of bibliographic databases. Prespecified criteria were used to identify 400 reports of randomized controlled trials from the reference lists of systematic reviews published in 2008 that evaluated physical therapy interventions. Eight databases (AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO, and PubMed) were searched for each trial report. The proportion of the 400 trial reports indexed by each database was calculated. The proportions of the 400 trial reports indexed by the databases were as follows: CENTRAL, 95%; PEDro, 92%; PubMed, 89%; EMBASE, 88%; CINAHL, 53%; AMED, 50%; Hooked on Evidence, 45%; and PsycINFO, 6%. Almost all of the trial reports (99%) were found in at least 1 database, and 88% were indexed by 4 or more databases. Four trial reports were uniquely indexed by a single database only (2 in CENTRAL and 1 each in PEDro and PubMed). The results are only applicable to searching for English-language published reports of randomized controlled trials evaluating physical therapy interventions. The 4 most comprehensive databases of trial reports evaluating physical therapy interventions were CENTRAL, PEDro, PubMed, and EMBASE. Clinicians seeking quick answers to clinical questions could search any of these databases knowing that all are reasonably comprehensive. PEDro, unlike the other 3 most complete databases, is specific to physical therapy, so studies not relevant to physical therapy are less likely to be retrieved. Researchers could use CENTRAL, PEDro, PubMed, and EMBASE in combination to conduct exhaustive searches for randomized trials in physical therapy.

A systematic review found that deviations from intention-to-treat are common in randomized trials and systematic reviews.

PubMed

Abraha, Iosief; Cozzolino, Francesco; Orso, Massimiliano; Marchesi, Mauro; Germani, Antonella; Lombardo, Guido; Eusebi, Paolo; De Florio, Rita; Luchetta, Maria Laura; Iorio, Alfonso; Montedori, Alessandro

2017-04-01

To describe the characteristics, and estimate the incidence, of trials included in systematic reviews deviating from the intention-to-treat (ITT) principle. A 5% random sample of reviews were selected (Medline 2006-2010). Trials from reviews were classified based on the ITT: (1) ITT trials (trials reporting standard ITT analyses); (2) modified ITT (mITT) trials (modified ITT; trials deviating from standard ITT); or (3) no ITT trials. Of 222 reviews, 81 (36%) included at least one mITT trial. Reviews with mITT trials were more likely to contain trials that used placebo, that investigated drugs, and that reported favorable results. The incidence of reviews with mITT trial ranged from 29% (17/58) to 48% (23/48). Of the 2,349 trials, 597 (25.4%) were classified as ITT trials, 323 (13.8%) as mITT trials, and 1,429 (60.8%) as no ITT trials. The mITT trials were more likely to have reported exclusions compared to studies classified as ITT trials and to have received funding. The reporting of the type of ITT may differ according to the clinical area and the type of intervention. Deviation from ITT in randomized controlled trials is a widespread phenomenon that significantly affects systematic reviews. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased Patient Enrollment to a Randomized Surgical Trial Through Equipoise Polling of an Expert Surgeon Panel.

PubMed

Ghogawala, Zoher; Schwartz, J Sanford; Benzel, Edward C; Magge, Subu N; Coumans, Jean Valery; Harrington, J Fred; Gelbs, Jared C; Whitmore, Robert G; Butler, William E; Barker, Fred G

2016-07-01

To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.

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.

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

PubMed

Doughty, R N; Rodgers, A; Sharpe, N; MacMahon, S

1997-04-01

Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Many multicenter trials had few events per center, requiring analysis via random-effects models or GEEs.

PubMed

Kahan, Brennan C; Harhay, Michael O

2015-12-01

Adjustment for center in multicenter trials is recommended when there are between-center differences or when randomization has been stratified by center. However, common methods of analysis (such as fixed-effects, Mantel-Haenszel, or stratified Cox models) often require a large number of patients or events per center to perform well. We reviewed 206 multicenter randomized trials published in four general medical journals to assess the average number of patients and events per center and determine whether appropriate methods of analysis were used in trials with few patients or events per center. The median number of events per center/treatment arm combination for trials using a binary or survival outcome was 3 (interquartile range, 1-10). Sixteen percent of trials had less than 1 event per center/treatment combination, 50% fewer than 3, and 63% fewer than 5. Of the trials which adjusted for center using a method of analysis which requires a large number of events per center, 6% had less than 1 event per center-treatment combination, 25% fewer than 3, and 50% fewer than 5. Methods of analysis that allow for few events per center, such as random-effects models or generalized estimating equations (GEEs), were rarely used. Many multicenter trials contain few events per center. Adjustment for center using random-effects models or GEE with model-based (non-robust) standard errors may be beneficial in these scenarios. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of online mindfulness-based interventions in improving mental health: A review and meta-analysis of randomised controlled trials.

PubMed

Spijkerman, M P J; Pots, W T M; Bohlmeijer, E T

2016-04-01

Mindfulness-based interventions (MBIs) are increasingly being delivered through the Internet. Whereas numerous meta-analyses have investigated the effectiveness of face-to-face MBIs in the context of mental health and well-being, thus far a quantitative synthesis of the effectiveness of online MBIs is lacking. The aim of this meta-analysis was to estimate the overall effects of online MBIs on mental health. Fifteen randomised controlled trials were included in this study. A random effects model was used to compute pre-post between-group effect sizes, and the study quality of each of the included trials was rated. Results showed that online MBIs have a small but significant beneficial impact on depression (g=0.29), anxiety (g=0.22), well-being (g=0.23) and mindfulness (g=0.32). The largest effect was found for stress, with a moderate effect size (g=0.51). For stress and mindfulness, exploratory subgroup analyses demonstrated significantly higher effect sizes for guided online MBIs than for unguided online MBIs. In addition, meta-regression analysis showed that effect sizes for stress were significantly moderated by the number of intervention sessions. Effect sizes, however, were not significantly related to study quality. The findings indicate that online MBIs have potential to contribute to improving mental health outcomes, particularly stress. Limitations, directions for future research and practical implications are discussed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis.

PubMed

Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

Intention-to-Treat Analysis in Partially Nested Randomized Controlled Trials with Real-World Complexity

ERIC Educational Resources Information Center

Schweig, Jonathan David; Pane, John F.

2016-01-01

Demands for scientific knowledge of what works in educational policy and practice has driven interest in quantitative investigations of educational outcomes, and randomized controlled trials (RCTs) have proliferated under these conditions. In educational settings, even when individuals are randomized, both experimental and control students are…

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…

Timing and Characteristics of Cumulative Evidence Available on Novel Therapeutic Agents Receiving Food and Drug Administration Accelerated Approval.

PubMed

Naci, Huseyin; Wouters, Olivier J; Gupta, Radhika; Ioannidis, John P A

2017-06-01

Policy Points: Randomized trials-the gold standard of evaluating effectiveness-constitute a small minority of existing evidence on agents given accelerated approval. One-third of randomized trials are in therapeutic areas outside of FDA approval and less than half evaluate the therapeutic benefits of these agents but use them instead as common backbone treatments. Agents receiving accelerated approval are often tested concurrently in several therapeutic areas. For most agents, no substantial time lag is apparent between the average start dates of randomized trials evaluating their effectiveness and those using them as part of background therapies. There appears to be a tendency for therapeutic agents receiving accelerated approval to quickly become an integral component of standard treatment, despite potential shortcomings in their evidence base. Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or nonrandomized, (2) explored whether they evaluated the FDA-approved indications, and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent's effectiveness. In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search of ClinicalTrials.gov identified 7,757 studies, which included 1,258,315 participants. Only one-third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411 out of 906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval ("evaluation" trials); others used these agents as common background treatment in both arms ("background" trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. Evaluation trials started on average 1.52 years (95% CI: 0.87 to 2.17) earlier than background trials. Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and nonrandomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment. © 2017 Milbank Memorial Fund.

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

PubMed

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

2016-01-01

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

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.

Adaptive adjustment of the randomization ratio using historical control data.

PubMed

Hobbs, Brian P; Carlin, Bradley P; Sargent, Daniel J

2013-01-01

Prospective trial design often occurs in the presence of 'acceptable' historical control data. Typically, these data are only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al., succeeded a similar trial reported by Saltz et al., and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS), characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial's frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure lead to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on preexisting information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare.

Nonlinear consolidation in randomly heterogeneous highly compressible aquitards

NASA Astrophysics Data System (ADS)

Zapata-Norberto, Berenice; Morales-Casique, Eric; Herrera, Graciela S.

2018-05-01

Severe land subsidence due to groundwater extraction may occur in multiaquifer systems where highly compressible aquitards are present. The highly compressible nature of the aquitards leads to nonlinear consolidation where the groundwater flow parameters are stress-dependent. The case is further complicated by the heterogeneity of the hydrogeologic and geotechnical properties of the aquitards. The effect of realistic vertical heterogeneity of hydrogeologic and geotechnical parameters on the consolidation of highly compressible aquitards is investigated by means of one-dimensional Monte Carlo numerical simulations where the lower boundary represents the effect of an instant drop in hydraulic head due to groundwater pumping. Two thousand realizations are generated for each of the following parameters: hydraulic conductivity ( K), compression index ( C c), void ratio ( e) and m (an empirical parameter relating hydraulic conductivity and void ratio). The correlation structure, the mean and the variance for each parameter were obtained from a literature review about field studies in the lacustrine sediments of Mexico City. The results indicate that among the parameters considered, random K has the largest effect on the ensemble average behavior of the system when compared to a nonlinear consolidation model with deterministic initial parameters. The deterministic solution underestimates the ensemble average of total settlement when initial K is random. In addition, random K leads to the largest variance (and therefore largest uncertainty) of total settlement, groundwater flux and time to reach steady-state conditions.

Mindfulness-based stress reduction for treating chronic headache: A systematic review and meta-analysis.

PubMed

Anheyer, Dennis; Leach, Matthew J; Klose, Petra; Dobos, Gustav; Cramer, Holger

2018-01-01

Background Mindfulness-based stress reduction/cognitive therapy are frequently used for pain-related conditions, but their effects on headache remain uncertain. This review aimed to assess the efficacy and safety of mindfulness-based stress reduction/cognitive therapy in reducing the symptoms of chronic headache. Data sources and study selection MEDLINE/PubMed, Scopus, CENTRAL, and PsychINFO were searched to 16 June 2017. Randomized controlled trials comparing mindfulness-based stress reduction/cognitive therapy with usual care or active comparators for migraine and/or tension-type headache, which assessed headache frequency, duration or intensity as a primary outcome, were eligible for inclusion. Risk of bias was assessed using the Cochrane Tool. Results Five randomized controlled trials (two on tension-type headache; one on migraine; two with mixed samples) with a total of 185 participants were included. Compared to usual care, mindfulness-based stress reduction/cognitive therapy did not improve headache frequency (three randomized controlled trials; standardized mean difference = 0.00; 95% confidence interval = -0.33,0.32) or headache duration (three randomized controlled trials; standardized mean difference = -0.08; 95% confidence interval = -1.03,0.87). Similarly, no significant difference between groups was found for pain intensity (five randomized controlled trials; standardized mean difference = -0.78; 95% confidence interval = -1.72,0.16). Conclusions Due to the low number, small scale and often high or unclear risk of bias of included randomized controlled trials, the results are imprecise; this may be consistent with either an important or negligible effect. Therefore, more rigorous trials with larger sample sizes are needed.

Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic.

PubMed

Annane, Djillali; Antona, Marion; Lehmann, Blandine; Kedzia, Cecile; Chevret, Sylvie

2012-01-01

To analyze the hurdles in implementing a randomized trial of corticosteroids for severe 2009 H1N1 influenza infections. This was an investigator-led, multicenter, randomized, placebo-controlled, double-blind trial of corticosteroids in ICU patients with 2009 H1N1 influenza pneumonia requiring mechanical ventilation. The feasibility of and hurdles in designing and initiating a phase III trial in a short-lived pandemic crisis were analyzed. The regulatory agency and ethics committee approved the study's scientific, financial, and ethical aspects within 4 weeks. Hydrocortisone and placebo were prepared centrally and shipped to participating hospitals within 6 weeks. The inclusion period started on November 9, 2009. From August 1, 2009 to March 8, 2010, only 205/224 ICU patients with H1N1 infections required mechanical ventilation. The peak of the wave was missed by 2-3 weeks and only 26 patients were randomized. The two main reasons for non-inclusion were patients' admission before the beginning of the trial and ICU personnel overwhelmed by clinical duties. Parallel rather than sequential regulatory and ethics approval, and preparation and masking of study drugs by local pharmacists would have allowed the study to start 1 month earlier and before the peak of the "flu" wave. A dedicated research team in each participating center would have increased the ratio of screened to randomized patients. This report highlights the main hurdles in implementing a randomized trial for a pandemic critical illness and proposes solutions for future trials.

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review.

PubMed

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-11-30

Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS). The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials. A systematic review of randomized controlled trials was conducted. Only trials that have reported significant FMS-related outcomes were included. Data relating to the components of hydrotherapy programs (exercise type, duration, frequency and intensity, environmental factors, and service delivery) were analyzed. Eleven randomized controlled trials were included in this review. Overall, the quality of trials was good. Aerobic exercise featured in all 11 trials and the majority of hydrotherapy programs included either a strengthening or flexibility component. Great variability was noted in both the environmental components of hydrotherapy programs and service delivery. Aerobic exercise, warm up and cool-down periods and relaxation exercises are common features of hydrotherapy programs that report significant FMS-related outcomes. Treatment duration of 60 minutes, frequency of three sessions per week and an intensity equivalent to 60%-80% maximum heart rate were the most commonly reported exercise components. Exercise appears to be the most important component of an effective hydrotherapy program for FMS, particularly when considering mental health-related outcomes.

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

PubMed Central

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

2015-01-01

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

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.

Methods for sample size determination in cluster randomized trials

PubMed Central

Rutterford, Clare; Copas, Andrew; Eldridge, Sandra

2015-01-01

Background: The use of cluster randomized trials (CRTs) is increasing, along with the variety in their design and analysis. The simplest approach for their sample size calculation is to calculate the sample size assuming individual randomization and inflate this by a design effect to account for randomization by cluster. The assumptions of a simple design effect may not always be met; alternative or more complicated approaches are required. Methods: We summarise a wide range of sample size methods available for cluster randomized trials. For those familiar with sample size calculations for individually randomized trials but with less experience in the clustered case, this manuscript provides formulae for a wide range of scenarios with associated explanation and recommendations. For those with more experience, comprehensive summaries are provided that allow quick identification of methods for a given design, outcome and analysis method. Results: We present first those methods applicable to the simplest two-arm, parallel group, completely randomized design followed by methods that incorporate deviations from this design such as: variability in cluster sizes; attrition; non-compliance; or the inclusion of baseline covariates or repeated measures. The paper concludes with methods for alternative designs. Conclusions: There is a large amount of methodology available for sample size calculations in CRTs. This paper gives the most comprehensive description of published methodology for sample size calculation and provides an important resource for those designing these trials. PMID:26174515

Effectiveness of a Parent Health Report in Increasing Fruit and Vegetable Consumption Among Preschoolers and Kindergarteners.

PubMed

Hunsaker, Sanita L; Jensen, Chad D

2017-05-01

To determine the effectiveness of a parent health report on fruit and vegetable consumption among preschoolers and kindergarteners. Pre-post open design trial and a randomized controlled trial. A university-sponsored preschool and kindergarten. A total of 63 parents of preschool and kindergarten students participated in the pre-post open design trial and 65 parents participated in the randomized controlled trial. Parents in intervention groups were given a parent health report providing information about their child's fruit and vegetable intake as well as recommendations for how to increase their child's fruit and vegetable consumption. Change in fruit and vegetable consumption. Latent growth curve modeling with Bayesian estimation. Vegetable consumption increased by 0.3 servings/d in the open trial and 0.65 servings/d in the randomized trial. Fruit consumption did not increase significantly in either study. Results from both an open trial and a randomized controlled trial suggested that the parent health report may be a beneficial tool to increase vegetable consumption in preschoolers and kindergarteners. Increases in vegetable consumption can lead to the establishment of lifelong habits of healthy vegetable intake and decrease risk for chronic diseases. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

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

2013-01-01

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

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

EPA Science Inventory

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

Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.

PubMed

Ghali, Jalal K; Anand, Inder S; Abraham, William T; Fonarow, Gregg C; Greenberg, Barry; Krum, Henry; Massie, Barry M; Wasserman, Scott M; Trotman, Marie-Louise; Sun, Yan; Knusel, Beat; Armstrong, Paul

2008-01-29

Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF. Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [-0.2, 1.0] g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > or = 1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups. In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed.

Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol

PubMed Central

2010-01-01

Background Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. Objective The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. Methods/Design Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082. PMID:20591191

Costs and cost-effectiveness of a mental health intervention for war-affected young persons: decision analysis based on a randomized controlled trial.

PubMed

McBain, Ryan K; Salhi, Carmel; Hann, Katrina; Salomon, Joshua A; Kim, Jane J; Betancourt, Theresa S

2016-05-01

One billion children live in war-affected regions of the world. We conducted the first cost-effectiveness analysis of an intervention for war-affected youth in sub-Saharan Africa, as well as a broader cost analysis. The Youth Readiness Intervention (YRI) is a behavioural treatment for reducing functional impairment associated with psychological distress among war-affected young persons. A randomized controlled trial was conducted in Freetown, Sierra Leone, from July 2012 to July 2013. Participants (n = 436, aged 15-24) were randomized to YRI (n = 222) or care as usual (n = 214). Functional impairment was indexed by the World Health Organization Disability Assessment Scale; scores were converted to quality-adjusted life years (QALYs). An 'ingredients approach' estimated financial and economic costs, assuming a societal perspective. Incremental cost-effectiveness ratios (ICERs) were also expressed in terms of gains across dimensions of mental health and schooling. Secondary analyses explored whether intervention effects were largest among those worst-off (upper quartile) at baseline. Retention at 6-month follow-up was 85% (n = 371). The estimated economic cost of the intervention was $104 per participant. Functional impairment was lower among YRI recipients, compared with controls, following the intervention but not at 6-month follow-up, and yielded an ICER of $7260 per QALY gained. At 8-month follow-up, teachers' interviews indicated that YRI recipients observed higher school enrolment [P < 0.001, odds ratio (OR) 8.9], denoting a cost of $431 per additional school year gained, as well as better school attendance (P = 0.007, OR 34.9) and performance (P = 0.03, effect size = -1.31). Secondary analyses indicated that the intervention was cost-effective among those worst-off at baseline, yielding an ICER of $3564 per QALY gained. The YRI is not cost-effective at a willingness-to-pay threshold of three times average gross domestic product per capita. However, results indicate that the YRI translated into a range of benefits, such as improved school enrolment, not captured by cost-effectiveness analysis. We also outline areas for modification to improve cost-effectiveness in future trials. clinicaltrials.gov Identifier: RPCGA-YRI-21003. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies

PubMed Central

Papanikolaou, Panagiotis N.; Christidi, Georgia D.; Ioannidis, John P.A.

2006-01-01

Background Information on major harms of medical interventions comes primarily from epidemiologic studies performed after licensing and marketing. Comparison with data from large-scale randomized trials is occasionally feasible. We compared evidence from randomized trials with that from epidemiologic studies to determine whether they give different estimates of risk for important harms of medical interventions. Methods We targeted well-defined, specific harms of various medical interventions for which data were already available from large-scale randomized trials (> 4000 subjects). Nonrandomized studies involving at least 4000 subjects addressing these same harms were retrieved through a search of MEDLINE. We compared the relative risks and absolute risk differences for specific harms in the randomized and nonrandomized studies. Results Eligible nonrandomized studies were found for 15 harms for which data were available from randomized trials addressing the same harms. Comparisons of relative risks between the study types were feasible for 13 of the 15 topics, and of absolute risk differences for 8 topics. The estimated increase in relative risk differed more than 2-fold between the randomized and nonrandomized studies for 7 (54%) of the 13 topics; the estimated increase in absolute risk differed more than 2-fold for 5 (62%) of the 8 topics. There was no clear predilection for randomized or nonrandomized studies to estimate greater relative risks, but usually (75% [6/8]) the randomized trials estimated larger absolute excess risks of harm than the nonrandomized studies did. Interpretation Nonrandomized studies are often conservative in estimating absolute risks of harms. It would be useful to compare and scrutinize the evidence on harms obtained from both randomized and nonrandomized studies. PMID:16505459

Population-Level Cost-Effectiveness of Implementing Evidence-Based Practices into Routine Care

PubMed Central

Fortney, John C; Pyne, Jeffrey M; Burgess, James F

2014-01-01

Objective The objective of this research was to apply a new methodology (population-level cost-effectiveness analysis) to determine the value of implementing an evidence-based practice in routine care. Data Sources/Study Setting Data are from sequentially conducted studies: a randomized controlled trial and an implementation trial of collaborative care for depression. Both trials were conducted in the same practice setting and population (primary care patients prescribed antidepressants). Study Design The study combined results from a randomized controlled trial and a pre-post-quasi-experimental implementation trial. Data Collection/Extraction Methods The randomized controlled trial collected quality-adjusted life years (QALYs) from survey and medication possession ratios (MPRs) from administrative data. The implementation trial collected MPRs and intervention costs from administrative data and implementation costs from survey. Principal Findings In the randomized controlled trial, MPRs were significantly correlated with QALYs (p = .03). In the implementation trial, patients at implementation sites had significantly higher MPRs (p = .01) than patients at control sites, and by extrapolation higher QALYs (0.00188). Total costs (implementation, intervention) were nonsignificantly higher ($63.76) at implementation sites. The incremental population-level cost-effectiveness ratio was $33,905.92/QALY (bootstrap interquartile range −$45,343.10/QALY to $99,260.90/QALY). Conclusions The methodology was feasible to operationalize and gave reasonable estimates of implementation value. PMID:25328029

The deterministic chaos and random noise in turbulent jet

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

Yao, Tian-Liang; Shanghai Institute of Space Propulsion, Shanghai 201112; Shanghai Engineering Research Center of Space Engine, Shanghai Institute of Space Propulsion, Shanghai 201112

2014-06-01

A turbulent flow is usually treated as a superposition of coherent structure and incoherent turbulence. In this paper, the largest Lyapunov exponent and the random noise in the near field of round jet and plane jet are estimated with our previously proposed method of chaotic time series analysis [T. L. Yao, et al., Chaos 22, 033102 (2012)]. The results show that the largest Lyapunov exponents of the round jet and plane jet are in direct proportion to the reciprocal of the integral time scale of turbulence, which is in accordance with the results of the dimensional analysis, and the proportionalitymore » coefficients are equal. In addition, the random noise of the round jet and plane jet has the same linear relation with the Kolmogorov velocity scale of turbulence. As a result, the random noise may well be from the incoherent disturbance in turbulence, and the coherent structure in turbulence may well follow the rule of chaotic motion.« less

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

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

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

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

Scientific publications from mainland China, Taiwan, and Hong Kong in integrative and complementary medicine journals: a ten-year literature survey.

PubMed

Li, Xiao-Qian; Tao, Kun-Ming; Zhou, Qing-Hui; Ling, Chang-Quan

2011-01-01

Practitioners and researchers from China, the largest user of complementary and alternative medicine (CAM), have been publishing an increasing number of scientific articles in world-famous CAM journals in recent years. However, the status of CAM research in the three major regions of China, the Mainland, Taiwan and Hong Kong has, until now, not been reported. In this study, we compared articles from these three regions published in international CAM journals from 2000 to 2009 using PubMed database and the Journal Citation Reports. The study results showed that the number of published articles from Mainland China increased significantly from 2000 to 2009, particularly since 2005. Meanwhile, the number of published articles from Taiwan also increased, whereas those from Hong Kong remained steady. Clinical trials and randomized controlled trials from Chinese authors both took a small percentage of the total. The impact factors of the journals in which these articles were published suggested similar academic levels whereas the average number of citation of articles from the Mainland was less than those from the other two regions. Journal of Ethnopharmacology, American Journal of Chinese Medicine, Journal of Alternative and Complementary Medicine and Evidence-based Complementary and Alternative Medicine were the most popular journals for Chinese authors.

Randomized Controlled Trial of a Preventive Intervention for Perinatal Depression in High-Risk Latinas

ERIC Educational Resources Information Center

Le, Huynh-Nhu; Perry, Deborah F.; Stuart, Elizabeth A.

2011-01-01

Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual…

Intraclass Correlations for Three-Level Multi-Site Cluster-Randomized Trials of Science Achievement

ERIC Educational Resources Information Center

Westine, Carl D.

2015-01-01

A cluster-randomized trial (CRT) relies on random assignment of intact clusters to treatment conditions, such as classrooms or schools (Raudenbush & Bryk, 2002). One specific type of CRT, a multi-site CRT (MSCRT), is commonly employed in educational research and evaluation studies (Spybrook & Raudenbush, 2009; Spybrook, 2014; Bloom,…

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

ERIC Educational Resources Information Center

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

2017-01-01

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

A 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…

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…

Outcomes from a School-Randomized Controlled Trial of Steps to Respect: A Bullying Prevention Program

ERIC Educational Resources Information Center

Brown, Eric C.; Low, Sabina; Smith, Brian H.; Haggerty, Kevin P.

2011-01-01

This study reports the outcomes of a randomized controlled trial of Steps to Respect: A Bullying Prevention Program conducted in 33 California elementary schools. Schools were matched on school demographic characteristics and assigned randomly to intervention or waitlisted control conditions. Outcome measures were obtained from (a) all school…

Sydney Playground Project: A Cluster-Randomized Trial to Increase Physical Activity, Play, and Social Skills

ERIC Educational Resources Information Center

Bundy, Anita; Engelen, Lina; Wyver, Shirley; Tranter, Paul; Ragen, Jo; Bauman, Adrian; Baur, Louise; Schiller, Wendy; Simpson, Judy M.; Niehues, Anita N.; Perry, Gabrielle; Jessup, Glenda; Naughton, Geraldine

2017-01-01

Background: We assessed the effectiveness of a simple intervention for increasing children's physical activity, play, perceived competence/social acceptance, and social skills. Methods: A cluster-randomized controlled trial was conducted, in which schools were the clusters. Twelve Sydney (Australia) primary schools were randomly allocated to…

After-School Multifamily Groups: A Randomized Controlled Trial Involving Low-Income, Urban, Latino Children

ERIC Educational Resources Information Center

McDonald, Lynn; Moberg, D. Paul; Brown, Roger; Rodriguez-Espiricueta, Ismael; Flores, Nydia I.; Burke, Melissa P.; Coover, Gail

2006-01-01

This randomized controlled trial evaluated a culturally representative parent engagement strategy with Latino parents of elementary school children. Ten urban schools serving low-income children from mixed cultural backgrounds participated in a large study. Classrooms were randomly assigned either either to an after-school, multifamily support…

The Walking School Bus and children's physical activity: A pilot cluster randomized controlled trial

USDA-ARS?s Scientific Manuscript database

To evaluate the impact of a "walking school bus" program on children's rates of active commuting to school and physical activity. We conducted a pilot cluster randomized controlled trial among 4th-graders from 8 schools in Houston, Texas (N = 149). Random allocation to treatment or control condition...

Randomized Clinical Trial Replication of a Psychosocial Treatment for Children with High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Thomeer, Marcus L.; Lopata, Christopher; Volker, Martin A.; Toomey, Jennifer A.; Lee, Gloria K.; Smerbeck, Audrey M.; Rodgers, Jonathan D.; McDonald, Christin A.; Smith, Rachael A.

2012-01-01

This replication randomized clinical trial examined the efficacy of a comprehensive psychosocial intervention for children aged 7 to 12 years with high-functioning autism spectrum disorders (HFASDs). Participants were randomly assigned to treatment or wait-list conditions. Treatment included instruction and therapeutic activities targeting social…

Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones.

PubMed

Goldfarb, David S; MacDonald, Patricia A; Gunawardhana, Lhanoo; Chefo, Solomon; McLean, Lachy

2013-11-01

Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation. In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥ 3 mm (as seen by multidetector computed tomography) received daily febuxostat at 80 mg, allopurinol at 300 mg, or placebo. The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid. Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance. Of 99 enrolled participants, 86 participants completed the study. Febuxostat led to significantly greater reduction in 24-hour urinary uric acid (-58.6%) than either allopurinol (-36.4%; P=0.003) or placebo (-12.7%; P<0.001). Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo. There was no change in stone size, stone number, or renal function. No new safety concerns were noted for either drug. Febuxostat (80 mg) lowered 24-hour urinary uric acid significantly more than allopurinol (300 mg) in stone formers with higher urinary uric acid excretion after 6 months of treatment. There was no change in stone size or number over the 6-month period.

Incidence and Predictors of reCurrent Restenosis After Drug-coated Balloon Angioplasty for Restenosis of a drUg-eluting Stent: The ICARUS Cooperation.

PubMed

Cassese, Salvatore; Xu, Bo; Habara, Seiji; Rittger, Harald; Byrne, Robert A; Waliszewski, Matthias; Pérez-Vizcayno, María José; Gao, Runlin; Kastrati, Adnan; Alfonso, Fernando

2017-09-12

The incidence and predictors of recurrent restenosis after drug-coated balloon (DCB) angioplasty for drug-eluting stent (DES) restenosis remain poorly studied. We sought to evaluate the incidence and predictors of recurrent restenosis among participants in randomized controlled trials receiving DCB angioplasty for DES restenosis. The clinical and lesion data of individuals enrolled in 6 randomized controlled trials of DCB angioplasty for DES restenosis were pooled. All patients included in this report were assigned to receive paclitaxel-coated balloon angioplasty with the SeQuent Please DCB (B Braun, Melsungen, Germany). The current analysis focused on participants with available follow-up angiography at 6 to 9 months. The incidence of recurrent restenosis, defined as diameter restenosis ≥ 50% in the in-segment area at follow-up angiography, and its clinical and angiographic predictors were evaluated. A total of 546 patients were combined in a single dataset. Angiographic follow-up at 6 to 9 months was available for 484 patients (88.6%) with 518 treated lesions. Recurrent restenosis was detected in 101 (20.8%) patients. On multivariable analysis, lesion length (OR, 1.58; 95%CI, 1.10-2.26; P=.012 for 5mm increase) and vessel size (OR, 1.42; 95%, 1.12-1.79; P=.003 for 0.5mm reduction) were independently associated with recurrent restenosis. In the largest cohort to date of individuals with angiographic surveillance after DCB angioplasty for DES restenosis, we demonstrated that recurrent restenosis occurs in approximately 1 out of 5 patients. Predictors of recurrent restenosis are increased lesion length and small vessel size. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: the Valsartan Heart Failure Trial (Val-HeFT).

PubMed

Latini, Roberto; Masson, Serge; Anand, Inder; Judd, Dianne; Maggioni, Aldo P; Chiang, Yann-Tong; Bevilacqua, Maurizio; Salio, Monica; Cardano, Paola; Dunselman, Peter H J M; Holwerda, Nicolaas J; Tognoni, Gianni; Cohn, Jay N

2002-11-05

Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known. Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or beta-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (+/-SEM) BNP increased from baseline by 23+/-5 pg/mL in the placebo group (n=1979) but decreased by 21+/-5 pg/mL (n=1940) in the valsartan group (P<0.0001). NE increased by 41+/-6 pg/mL (n=1979) and 12+/-6 pg/mL (n=1941) for placebo and valsartan, respectively (P=0.0003). Concomitant therapy with both ACE inhibitors and beta-blockers significantly reduced the effect of valsartan on BNP but not on NE (P for interaction=0.0223 and 0.2289, respectively). In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT.

Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

PubMed

Espeland, Mark A; Rapp, Stephen R; Manson, JoAnn E; Goveas, Joseph S; Shumaker, Sally A; Hayden, Kathleen M; Weitlauf, Julie C; Gaussoin, Sarah A; Baker, Laura D; Padula, Claudia B; Hou, Lifang; Resnick, Susan M

2017-06-01

Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age. Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos. Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase. CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain stimulation and constraint for perinatal stroke hemiparesis

PubMed Central

Andersen, John; Herrero, Mia; Nettel-Aguirre, Alberto; Carsolio, Lisa; Damji, Omar; Keess, Jamie; Mineyko, Aleksandra; Hodge, Jacquie; Hill, Michael D.

2016-01-01

Objective: To determine whether the addition of repetitive transcranial magnetic stimulation (rTMS) and/or constraint-induced movement therapy (CIMT) to intensive therapy increases motor function in children with perinatal stroke and hemiparesis. Methods: A factorial-design, blinded, randomized controlled trial (clinicaltrials.gov/NCT01189058) assessed rTMS and CIMT effects in hemiparetic children (aged 6–19 years) with MRI-confirmed perinatal stroke. All completed a 2-week, goal-directed, peer-supported motor learning camp randomized to daily rTMS, CIMT, both, or neither. Primary outcomes were the Assisting Hand Assessment and the Canadian Occupational Performance Measure at baseline, and 1 week, 2 and 6 months postintervention. Outcome assessors were blinded to treatment. Interim safety analyses occurred after 12 and 24 participants. Intention-to-treat analysis examined treatment effects over time (linear mixed effects model). Results: All 45 participants completed the trial. Addition of rTMS, CIMT, or both doubled the chances of clinically significant improvement. Assisting Hand Assessment gains at 6 months were additive and largest with rTMS + CIMT (β coefficient = 5.54 [2.57–8.51], p = 0.0004). The camp alone produced large improvements in Canadian Occupational Performance Measure scores, maximal at 6 months (Cohen d = 1.6, p = 0.002). Quality-of-life scores improved. Interventions were well tolerated and safe with no decrease in function of either hand. Conclusions: Hemiparetic children participating in intensive, psychosocial rehabilitation programs can achieve sustained functional gains. Addition of CIMT and rTMS increases the chances of improvement. Classification of evidence: This study provides Class II evidence that combined rTMS and CIMT enhance therapy-induced functional motor gains in children with stroke-induced hemiparetic cerebral palsy. PMID:27029628

A randomized trial of peer review: the UK National Chronic Obstructive Pulmonary Disease Resources and Outcomes Project: three-year evaluation.

PubMed

Roberts, Christopher M; Stone, Robert A; Buckingham, Rhona J; Pursey, Nancy A; Lowe, Derek; Potter, Jonathan M

2012-06-01

Peer review has been widely used within the National Health Service to facilitate health quality improvement but evaluation has been limited particularly over the longer-term. Change within the National Health Service (NHS) can take a prolonged period--1-2 years--to occur. We report here a 3-year evaluation of the largest randomized trial of peer review ever conducted in the UK. To evaluate whether targeted mutual peer review of respiratory units brings about improvements in services for chronic obstructive pulmonary disease (COPD) over 3 years. The peer review intervention was a reciprocal supportive exercise that included clinicians, hospital management, commissioners and patients, which focused on the quality of the provision of four specific evidence-based aspects of COPD care. Follow-up at 36 months demonstrated limited significant quantitative differences in the quality of services offered in the two groups but a strong trend in favour of intervention sites. Qualitative data suggested many benefits of peer review in most but not all intervention units and some control teams. The data identify factors that promote and obstruct change. The findings demonstrate significant change in service provision over 3 years in both control and intervention sites with great variability in both groups. The combined quantitative and qualitative findings indicate that targeted mutual peer review is associated with improved quality of care, improvements in service delivery and with changes within departments that promote and are precursors to quality improvement. The generic findings of this study have potential implications for the application of peer review throughout the NHS. © 2011 Blackwell Publishing Ltd.

A tailored educational intervention improves doctor's performance in managing depression: a randomized controlled trial.

PubMed

Shirazi, Mandana; Lonka, Kirsti; Parikh, Sagar V; Ristner, Gunilla; Alaeddini, Farshid; Sadeghi, Majid; Wahlstrom, Rolf

2013-02-01

To assess the effects of a tailored and activating educational intervention, based on a three-stage modified Prochaska model of readiness-to-change, on the performance of general physicians in primary care (GPs) regarding management of depressive disorders. Parallel group, randomized control trial. Primary hypothesis was that performance would improve by 20 percentage units in the intervention arm. The setting was primary care in southern Tehran. The participants were 192 GPs stratified on stage of readiness-to-change, sex, age and work experience. The intervention was a 2-day interactive workshop for a small group of GPs' at a higher stage of readiness-to-change ('intention') and a 2-day interactive large group meeting for those with lower propensity to change ('attitude') at the pre-assessment. GPs in the control arm participated in a standard educational programme on the same topic. The main outcome measures were validated tools to assess GPs' performance by unannounced standardized patients, regarding diagnosis and treatment of depressive disorders. The assessments were made 2 months before and 2 months after the intervention. GPs in the intervention arm significantly improved their overall mean scores for performance regarding both diagnosis, with an intervention effect of 14 percentage units (P = 0.007), and treatment and referral, with an intervention effect of 20 percentage units (P < 0.0001). The largest improvement after the intervention appeared in the small group: 30 percentage units for diagnosis (P = 0.027) and 29 percentage units for treatment and referral (P < 0.0001). Activating learning methods, tailored according to the participants' readiness to change, improved clinical performance of GPs in continuing medical education and can be recommended for continuing professional development. © 2011 Blackwell Publishing Ltd.

Overcoming Recruitment Challenges of Web-based Interventions for Tobacco Use: The Case of Web-based Acceptance and Commitment Therapy for Smoking Cessation

PubMed Central

Heffner, Jaimee L; Wyszynski, Christopher M; Comstock, Bryan; Mercer, Laina D.; Bricker, Jonathan

2013-01-01

Web-based behavioral interventions for substance use are being developed at a rapid pace, yet there is a dearth of information regarding the most effective methods for recruiting participants into web-based intervention trials. In this paper, we describe our successful recruitment of participants into a pilot trial of web-based Acceptance and Commitment Therapy (ACT) for smoking cessation and compare traditional and web-based methods of recruitment in terms of their effects on baseline participant characteristics, association with study retention and treatment outcome, yield, and cost-effectiveness. Over a 10-week period starting June 15, 2010, we recruited 222 smokers for a web-based smoking cessation study using a variety of recruitment methods. The largest portion of randomized participants were recruited through Google AdWords (36%), followed by medical Internet media (23%), standard media (14%), word of mouth (12%), broadcast emails (11%), and social media (6%). Recruitment source was not related to baseline participant characteristics, 3-month data retention, or 30-day point prevalence smoking abstinence at the 3-month outcome assessment. Cost per randomized participant ranged from $5.27/participant for word of mouth to $172.76/participant for social media, with a mean cost of $42.48/participant. Our diversified approach to recruitment, including both traditional and web-based methods, enabled timely enrollment of participants into the study. Because there was no evidence of a substantive difference in baseline characteristics, retention, or outcomes based on recruitment channel, the yield and cost-effectiveness of recruitment methods may be the more critical considerations in developing a feasible recruitment plan for a web-based smoking cessation intervention study. PMID:23770645

Overcoming recruitment challenges of web-based interventions for tobacco use: the case of web-based acceptance and commitment therapy for smoking cessation.

PubMed

Heffner, Jaimee L; Wyszynski, Christopher M; Comstock, Bryan; Mercer, Laina D; Bricker, Jonathan

2013-10-01

Web-based behavioral interventions for substance use are being developed at a rapid pace, yet there is a dearth of information regarding the most effective methods for recruiting participants into web-based intervention trials. In this paper, we describe our successful recruitment of participants into a pilot trial of web-based Acceptance and Commitment Therapy (ACT) for smoking cessation and compare traditional and web-based methods of recruitment in terms of their effects on baseline participant characteristics, association with study retention and treatment outcome, yield, and cost-effectiveness. Over a 10-week period starting June 15, 2010, we recruited 222 smokers for a web-based smoking cessation study using a variety of recruitment methods. The largest portion of randomized participants were recruited through Google AdWords (36%), followed by medical Internet media (23%), standard media (14%), word of mouth (12%), broadcast emails (11%), and social media (6%). Recruitment source was not related to baseline participant characteristics, 3-month data retention, or 30-day point prevalence smoking abstinence at the 3-month outcome assessment. Cost per randomized participant ranged from $5.27/participant for word of mouth to $172.76/participant for social media, with a mean cost of $42.48/participant. Our diversified approach to recruitment, including both traditional and web-based methods, enabled timely enrollment of participants into the study. Because there was no evidence of a substantive difference in baseline characteristics, retention, or outcomes based on recruitment channel, the yield and cost-effectiveness of recruitment methods may be the more critical considerations in developing a feasible recruitment plan for a web-based smoking cessation intervention study. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recruiting participants with peripheral arterial disease for clinical trials: experience from the Study to Improve Leg Circulation (SILC).

PubMed

McDermott, Mary M; Domanchuk, Kathryn; Dyer, Alan; Ades, Philip; Kibbe, Melina; Criqui, Michael H

2009-03-01

To describe the success of diverse recruitment methods in a randomized controlled clinical trial of exercise in persons with peripheral arterial disease (PAD). An analysis of recruitment sources conducted for the 746 men and women completing a baseline visit for the study to improve leg circulation (SILC), a randomized controlled trial of exercise for patients with PAD. For each recruitment source, we determined the number of randomized participants, the rate of randomization among those completing a baseline visit, and cost per randomized participant. Of the 746 individuals who completed a baseline visit, 156 were eligible and randomized. The most frequent sources of randomized participants were newspaper advertising (n = 67), mailed recruitment letters to patients with PAD identified at the study medical center (n = 25), and radio advertising (n = 18). Costs per randomized participant were $2750 for television advertising, $2167 for Life Line Screening, $2369 for newspaper advertising, $3931 for mailed postcards to older community dwelling men and women, and $5691 for radio advertising. Among those completing a baseline visit, randomization rates ranged from 10% for those identified from radio advertising to 32% for those identified from the Chicago Veterans Administration and 33% for those identified from posted flyers. Most participants in a randomized controlled trial of exercise were recruited from newspaper advertising and mailed recruitment letters to patients with known PAD. The highest randomization rates after a baseline visit occurred among participants identified from posted flyers and mailed recruitment letters to PAD patients.

Effectiveness of a parental training programme in enhancing the parent–child relationship and reducing harsh parenting practices and parental stress in preparing children for their transition to primary school: a randomised controlled trial

PubMed Central

2013-01-01

Background Entering primary school is an important childhood milestone, marking the beginning of a child’s formal education. Yet the change creates a time of vulnerability for the child, the parents and the parent–child relationship. Failure to adjust to the transition may place the family in a psychologically devastating position. The aims of this study were to test the effectiveness of a parental training programme in enhancing the parent–child relationship and decreasing parental stress by reducing harsh parenting in preparing children for the transition to primary school. Methods A randomised controlled trial incorporating a two-group pre-test and repeated post-test was conducted in one of the largest public housing estates in Hong Kong. A total of 142 parents were recruited, with 72 parents randomly assigned to the experimental group and 70 to the control group. Harsh parenting practices, parent–child relationships and parental stress were assessed. Results In comparison to parents in the control group, those in the experimental group engaged in less harsh parenting practices and reported better parent–child relationships. However, parental stress scores did not differ significantly between the two groups. Conclusion This study addressed a gap in the literature by examining the effectiveness of the training programme for enhancing parent–child relationship and decreasing parental stress at the time of a child’s transition to primary school. The findings from this study provide empirical evidence of the effectiveness of the parental training programme and highlight the significance of parenting in promoting a smooth transition for children from kindergarten to primary 1. Trial registration ClinicalTrials.gov: NCT01845948. PMID:24237718

New Developments in the Prophylactic Drug Treatment of Pediatric Migraine: What Is New in 2017 and Where Does It Leave Us?

PubMed

Kacperski, Joanne; Bazarsky, Allyson

2017-08-01

Headaches in children are quite common; however, the study and characterization of headache disorders in the pediatric age group has historically been limited. Because of the lack of controlled studies on prophylactic treatment of headache disorders in this age group, the diagnosis of migraine rests on criteria similar those in adults. Likewise, data from adult studies is often inferred and applied to children. Although it appears that many preventives are safe in children, currently none are FDA or EMA approved for this age group. Consequently, many children who present to their primary care physicians with migraines do not receive any preventive therapy despite experiencing significant disability. Controlled clinical trials investigating the use of preventive medications in children have suffered from high placebo response rates. The shorter duration of headaches and other characteristic features seen in children are such that designing randomized controlled trials in this age group is more problematic and limiting. Treatment practices vary widely, even among specialists, due to the absence of evidence-based guidelines from clinical trials. The Childhood and Adolescent Migraine Prevention Study (CHAMP) was developed to examine the effectiveness of two of the most widely prescribed preventive medications for pediatric migraine and help narrow this gap. To date, it has been the largest enrolling study of its kind within the pediatric migraine world; its results and implications will be discussed and considered here. The CHAMP trial was discontinued early on account of futility and exhibited that neither of two preventive medications for pediatric migraine was more effective than placebo in reducing the number of headache days over a period of 24 weeks. Subjects in the amitriptyline and topiramate groups had higher rates of adverse events than those who had received placebo.

Comparison of In-Patient Costs for Children Treated on the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group

PubMed Central

Getz, Kelly D.; Li, Yimei; Alonzo, Todd A.; Hall, Matthew; Gerbing, Robert B.; Sung, Lillian; Huang, Yuan-Shung; Arnold, Staci; Seif, Alix E.; Miller, Tamara P.; Bagatell, Rochelle; Fisher, Brian T.; Adamson, Peter C.; Gamis, Alan; Keren, Ron; Aplenc, Richard

2015-01-01

Background A better understanding of drivers of treatment costs may help identify effective cost containment strategies and prioritize resources. We aimed to develop a method for estimating inpatient costs for pediatric patients with acute myeloid leukemia (AML) enrolled on NCI-funded Phase III trials, compare costs between AAML0531 treatment arms (standard chemotherapy ± gemtuzumab ozogamicin (GMTZ)), and evaluate primary drivers of costs for newly diagnosed pediatric AML. Procedure Patients from the AAML0531 trial were matched on hospital, sex, and dates of birth and diagnosis to the Pediatric Health Information Systems (PHIS) database to obtain daily billing data. Inpatient treatment costs were calculated as adjusted charges multiplied by hospital-specific cost-to-charge ratios. Generalized linear models were used to compare costs between treatment arms and courses, and by patient characteristics. Results Inpatient costs did not differ by randomized treatment arm. Costs varied by course with stem cell transplant being most expensive, followed by Intensification II (cytarabine/mitoxantrone) and Induction I (cytarabine/daunorubicin/etoposide). Room/board and pharmacy were the largest contributors to inpatient treatment cost, representing 74% of the total cost. Higher AML risk group (P = 0.0003) and older age (P < 0.0001) were associated with significantly higher daily inpatient cost. Conclusions Costs from external data sources can be successfully integrated into NCI-funded Phase III clinical trials. Inpatient treatment costs did not differ by GMTZ exposure but varied by chemotherapy course. Variation in cost by course was driven by differences in duration of hospitalization through room/board charges as well as increased clinical and pharmacy charges in specific courses. Pediatr Blood Cancer PMID:25946708

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia.

PubMed

Montgomery, John H; Byerly, Matthew; Carmody, Thomas; Li, Baitao; Miller, Daniel R; Varghese, Femina; Holland, Rhiannon

2004-12-01

The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding). A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed. Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05). While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.

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

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

PubMed

Spence, Jessica; Belley-Côté, Emilie; Lee, Shun Fu; Bangdiwala, Shrikant; Whitlock, Richard; LeManach, Yannick; Syed, Summer; Lamy, Andre; Jacobsohn, Eric; MacIsaac, Sarah; Devereaux, P J; Connolly, Stuart

2018-07-01

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).

Adaptive adjustment of the randomization ratio using historical control data

PubMed Central

Hobbs, Brian P.; Carlin, Bradley P.; Sargent, Daniel J.

2013-01-01

Background Prospective trial design often occurs in the presence of “acceptable” [1] historical control data. Typically this data is only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. Purpose We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al. [2], succeeded a similar trial reported by Saltz et al. [3], and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. Methods The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS) characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors [4] are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial’s frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Results Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure leads to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Limitations Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. Conclusions The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on pre-existing information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare. PMID:23690095

Developing a Reporting Guideline for Social and Psychological Intervention Trials

PubMed Central

Mayo-Wilson, Evan; Hopewell, Sally; Macdonald, Geraldine; Moher, David; Grant, Sean

2013-01-01

Understanding randomized controlled trials of complex social and psychological interventions requires a detailed description of the interventions tested and the methods used to evaluate them. However, randomized controlled trial reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting hinders the optimal use of research, wastes resources, and fails to meet ethical obligations to research participants and consumers. We explain how reporting guidelines have improved the quality of reports in medicine, and describe the ongoing development of a new reporting guideline for randomized controlled trials: an extension of the Consolidated Standards of Reporting Trials for social and psychological interventions. We invite readers to participate in the project by visiting our Web site, to help us reach the best-informed consensus on these guidelines (http://tinyurl.com/consort-study). PMID:23947317

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

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

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

Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials.

PubMed

Saad, F; Ivanescu, C; Phung, D; Loriot, Y; Abhyankar, S; Beer, T M; Tombal, B; Holmstrom, S

2017-03-01

We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments. First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score -16.95 (-26.47, -7.44) and -9.69 (-16.10, -3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change -0.24 (-0.39, -0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone. SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL.

Using a network-based approach and targeted maximum likelihood estimation to evaluate the effect of adding pre-exposure prophylaxis to an ongoing test-and-treat trial.

PubMed

Balzer, Laura; Staples, Patrick; Onnela, Jukka-Pekka; DeGruttola, Victor

2017-04-01

Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger impact of pre-exposure prophylaxis. Offering pre-exposure prophylaxis to serodiscordant couples resulted in the largest reductions in HIV incidence (2% reduction), and the ring-based strategy had little impact (0% reduction). The joint effect was larger than either individual effect with reductions in the 7-year incidence ranging from 4.5% to 8.8%. Targeted maximum likelihood estimation, data-adaptively adjusting for baseline covariates, substantially improved power over the unadjusted analysis, while maintaining nominal confidence interval coverage. Our simulation study suggests that nesting a pre-exposure prophylaxis study within an ongoing trial can lead to combined intervention effects greater than those of universal test-and-treat alone and can provide information about the efficacy of pre-exposure prophylaxis in the presence of high coverage of treatment for HIV+ persons.

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.

Pilot randomized controlled trial of dialectical behavior therapy group skills training for ADHD among college students.

PubMed

Fleming, Andrew P; McMahon, Robert J; Moran, Lyndsey R; Peterson, A Paige; Dreessen, Anthony

2015-03-01

ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications.

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis

PubMed Central

Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Background Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. Methods We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Results Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24–0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04–5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Conclusion Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000025344. PMID:29293586

Brief Strategic Family Therapy versus Treatment as Usual: Results of a Multisite Randomized Trial for Substance Using Adolescents

ERIC Educational Resources Information Center

Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Rohrbaugh, Michael; Shoham, Varda; Bachrach, Ken; Miller, Michael; Burlew, Kathleen A.; Hodgkins, Candy; Carrion, Ibis; Vandermark, Nancy; Schindler, Eric; Werstlein, Robert; Szapocznik, Jose

2011-01-01

Objective: To determine the effectiveness of brief strategic family therapy (BSFT; an evidence-based family therapy) compared to treatment as usual (TAU) as provided in community-based adolescent outpatient drug abuse programs. Method: A randomized effectiveness trial in the National Drug Abuse Treatment Clinical Trials Network compared BSFT to…

New clinical trial to study long-term progression of brain and spine cancers | Center for Cancer Research

Cancer.gov

Dr. Mark Gilbert, Chief, Neuro-Oncology Branch, describes an ambitious new clinical trial that, for the first time, will study the long-term progression of brain and spine cancers. The 10,000 patient trial is the largest of its kind and will follow patients throughout the course of their disease. In addition to identifying optimal treatments for common brain and spine cancers, the study focuses on treatment discovery for rare, overlooked cancers.

[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].

PubMed

Sun, Yan-nan; Lei, Fei-fei; Cao, Yan-li; Fu, Min-kui

2010-02-01

To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.

Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials.

PubMed

Quist-Nelson, Johanna; Parker, Pamela; Mokhtari, Neggin; Di Sarno, Rossana; Saccone, Gabriele; Berghella, Vincenzo

2018-03-31

Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72). Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes. Copyright © 2018 Elsevier Inc. All rights reserved.

Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

PubMed

Ivanov, Alexander; Kaczkowska, Beata A; Khan, Saadat A; Ho, Jean; Tavakol, Morteza; Prasad, Ashok; Bhumireddy, Geetha; Beall, Allan F; Klem, Igor; Mehta, Parag; Briggs, William M; Sacchi, Terrence J; Heitner, John F

2017-01-01

Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

True fir spacing trials: 10-year results.

Treesearch

Robert O. Curtis

2008-01-01

Eighteen precommercial thinning trials were established in true fir-hemlock stands in the Olympic Mountains and the west side of the Cascade Range during the period 1987 through 1994. This paper updates a previous report, with results for the first 10 years after establishment. Results are given for (1) all trees, (2) the largest 80 per acre of any species, and (3)...

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.

Long-Term Follow-up of Participants with Heart Failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

PubMed Central

Piller, Linda B.; Baraniuk, Sarah; Simpson, Lara M.; Cushman, William C.; Massie, Barry M.; Einhorn, Paula T.; Oparil, Suzanne; Ford, Charles E.; Graumlich, James F.; Dart, Richard A.; Parish, David C.; Retta, Tamrat M.; Cuyjet, Aloysius B.; Jafri, Syed Z.; Furberg, Curt D.; Saklayen, Mohammad G.; Thadani, Udho; Probstfield, Jeffrey L.; Davis, Barry R.

2011-01-01

Background In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/day) and lisinopril (10-40 mg/day) arms compared with the chlorthalidone (12.5-25 mg/day) arm . Similar to other studies, mortality rates following new-onset HF were very high (≥50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases. Methods and Results Using national databases, post-trial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%) with no significant differences by randomized treatment arm. Conclusions Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with development of HF is to be addressed. PMID:21969009

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

PubMed

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

2014-04-01

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

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

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

PubMed

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

2014-11-01

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

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high. Copyright © 2017 Elsevier Inc. All rights reserved.

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%) had no identifiable data collected from any research participants. Overall, only three trials (9%) indicated that a waiver of consent had been granted by a research ethics committee. When considering the combined requirement of research ethics review and informed consent (or a waiver), only one in three studies were compliant. Conclusion The ethical conduct and reporting of key ethical protections in stepped wedge trials, namely, research ethics review and informed consent, are inadequate. We recommend that stepped wedge trials be classified as research and reviewed and approved by a research ethics committee. We also recommend that researchers appropriately identify research participants (which may include health professionals), seek informed consent or appeal to an ethics committee for a waiver of consent, and include explicit details of research ethics approval and informed consent in the trial report.

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

ERIC Educational Resources Information Center

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

2015-01-01

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

Interventions to Improve Medication Adherence among Older Adults: Meta-Analysis of Adherence Outcomes among Randomized Controlled Trials

ERIC Educational Resources Information Center

Conn, Vicki S.; Hafdahl, Adam R.; Cooper, Pamela S.; Ruppar, Todd M.; Mehr, David R.; Russell, Cynthia L.

2009-01-01

Purpose: This study investigated the effectiveness of interventions to improve medication adherence (MA) in older adults. Design and Methods: Meta-analysis was used to synthesize results of 33 published and unpublished randomized controlled trials. Random-effects models were used to estimate overall mean effect sizes (ESs) for MA, knowledge,…

Testing a Violence-Prevention Intervention for Incarcerated Women Using a Randomized Control Trial

ERIC Educational Resources Information Center

Kubiak, Sheryl Pimlott; Kim, Woo Jong; Fedock, Gina; Bybee, Deborah

2015-01-01

Objective: Beyond Violence (BV), a new prevention program for women with assaultive offenses, demonstrated feasibility in previous studies. This study's purpose is to assess the efficacy of BV using a randomized control trial. Method: Eligible women were randomly assigned to treatment as usual (TAU) and the experimental condition (BV). Measures of…

Randomized Controlled Trial in Clinical Settings to Evaluate Effectiveness of Coping Skills Education Used with Progressive Tinnitus Management

ERIC Educational Resources Information Center

Henry, James A.; Thielman, Emily J.; Zaugg, Tara L.; Kaelin, Christine; Schmidt, Caroline J.; Griest, Susan; McMillan, Garnett P.; Myers, Paula; Rivera, Izel; Baldwin, Robert; Carlson, Kathleen

2017-01-01

Purpose: This randomized controlled trial evaluated, within clinical settings, the effectiveness of coping skills education that is provided with progressive tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300 veterans were randomized to either PTM intervention or 6-month wait-list control. The PTM intervention…

Marital Status and Satisfaction Five Years Following a Randomized Clinical Trial Comparing Traditional versus Integrative Behavioral Couple Therapy

ERIC Educational Resources Information Center

Christensen, Andrew; Atkins, David C.; Baucom, Brian; Yi, Jean

2010-01-01

Objective: To follow distressed married couples for 5 years after their participation in a randomized clinical trial. Method: A total of 134 chronically and seriously distressed married couples were randomly assigned to approximately 8 months of either traditional behavioral couple therapy (TBCT; Jacobson & Margolin, 1979) or integrative…

Randomized Controlled Trial of the Resilience and Coping Intervention (RCI) with Undergraduate University Students

ERIC Educational Resources Information Center

Houston, J. Brian; First, Jennifer; Spialek, Matthew L.; Sorenson, Mary E.; Mills-Sandoval, Toby; Lockett, McKenzie; First, Nathan L.; Nitiéma, Pascal; Allen, Sandra F.; Pfefferbaum, Betty

2017-01-01

Objective: The purpose of this pilot study was to evaluate the Resilience and Coping Intervention (RCI) with college students. Participants: College students (aged 18-23) from a large Midwest US university who volunteered for a randomized controlled trial during the 2015 spring semester. Methods: College students were randomly assigned to an…

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results from a 2-Year Randomized Trial

ERIC Educational Resources Information Center

Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

2011-01-01

Objective: To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method: Early course schizophrenia outpatients (N = 58) were randomly assigned to cognitive enhancement therapy (CET) or an enriched supportive therapy (EST) control and…

Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

2016-01-01

This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual…

Evaluating the Collaborative Strategic Reading Intervention: An Overview of Randomized Controlled Trial Options

ERIC Educational Resources Information Center

Hitchcock, John H.; Kurki, Anja; Wilkins, Chuck; Dimino, Joseph; Gersten, Russell

2009-01-01

When attempting to determine if an intervention has a causal impact, the "gold standard" of program evaluation is the randomized controlled trial (RCT). In education studies random assignment is rarely feasible at the student level, making RCTs harder to conduct. School-level assignment is more common but this often requires considerable resources…

Maternal Dietary Counseling Reduces Consumption of Energy-Dense Foods among Infants: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Vitolo, Marcia Regina; Bortolini, Gisele Ane; Campagnolo, Paula Dal Bo; Hoffman, Daniel J.

2012-01-01

Objective: To evaluate the impact of a dietary counseling in reducing the intake of energy-dense foods by infants. Design: A randomized controlled trial. Setting and Participants: Sao Leopoldo, Brazil. Mothers and infants of a low-income-group population were randomized into intervention (n = 163) and received dietary counseling during 10 home…

Effect of Educational Package on Lifestyle of Primiparous Mothers during Postpartum Period: A Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

Khodabandeh, Farzaneh; Mirghafourvand, Mojgan; KamaliFard, Mahin; Mohammad-Alizadeh-Charandabi, Sakineh; Asghari Jafarabadi, Mohammad

2017-01-01

A healthy lifestyle is important for mothers during the postpartum period. This study was conducted to determine the effects of a lifestyle educational package in primiparous women. This randomized clinical trial was conducted on 220 mothers assigned to two groups using block randomization. In the intervention group, the mothers received…

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

ERIC Educational Resources Information Center

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

2018-01-01

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

Cognitive-Behavioral Treatment for Panic Disorder with Agoraphobia: A Randomized, Controlled Trial and Cost-Effectiveness Analysis

ERIC Educational Resources Information Center

Roberge, Pasquale; Marchand, Andre; Reinharz, Daniel; Savard, Pierre

2008-01-01

A randomized, controlled trial was conducted to examine the cost-effectiveness of cognitive-behavioral treatment (CBT) for panic disorder with agoraphobia. A total of 100 participants were randomly assigned to standard (n = 33), group (n = 35), and brief (n = 32) treatment conditions. Results show significant clinical and statistical improvement…

Mediating Parent Learning to Promote Social Communication for Toddlers with Autism: Effects from a Randomized Controlled Trial

ERIC Educational Resources Information Center

Schertz, Hannah H.; Odom, Samuel L.; Baggett, Kathleen M.; Sideris, John H.

2018-01-01

A randomized controlled trial was conducted to evaluate effects of the Joint Attention Mediated Learning (JAML) intervention. Toddlers with autism spectrum disorders (ASD) aged 16-30 months (n = 144) were randomized to intervention and community control conditions. Parents, who participated in 32 weekly home-based sessions, followed a mediated…

Impact of Patient Education on Influenza Vaccine Uptake among Community-Dwelling Elderly: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Ka Chun; Mui, Carlo; Chiu, Wing Yan; Ng, Yuk Yiu; Chen, Matthew H. Y.; Ho, Pui Hung; Kwok, Chun Pong; Lam, Suki S. M.; Wong, Chun Yip; Wong, Kit Yee; Pang, Herbert H.

2017-01-01

This randomized controlled trial aimed to test the effectiveness of brief face-to-face patient education in increasing influenza vaccination rate among elderly in the community. Recruitment and intervention were conducted at two general outpatient clinics in Hong Kong. 529 eligible patients were randomly assigned to intervention or control group…

Improving Young English Learners' Language and Literacy Skills through Teacher Professional Development: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Babinski, Leslie M.; Amendum, Steven J.; Knotek, Steven E.; Sánchez, Marta; Malone, Patrick

2018-01-01

Using a randomized controlled trial, we tested a new teacher professional development program for increasing the language and literacy skills of young Latino English learners with 45 teachers and 105 students in 12 elementary schools. School-based teams randomly assigned to the intervention received professional development focused on cultural…

Improving Classroom Learning Environments by Cultivating Awareness and Resilience in Education (CARE): Results of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Jennings, Patricia A.; Frank, Jennifer L.; Snowberg, Karin E.; Coccia, Michael A.; Greenberg, Mark T.

2013-01-01

Cultivating Awareness and Resilience in Education (CARE for Teachers) is a mindfulness-based professional development program designed to reduce stress and improve teachers' performance and classroom learning environments. A randomized controlled trial examined program efficacy and acceptability among a sample of 50 teachers randomly assigned to…

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…

A Randomized Controlled Trial of a Standardized Behavior Management Intervention for Students with Externalizing Behavior

ERIC Educational Resources Information Center

Forster, Martin; Sundell, Knut; Morris, Richard J.; Karlberg, Martin; Melin, Lennart

2012-01-01

This study reports the results from a Swedish randomized controlled trial of a standardized behavior management intervention. The intervention targeted students with externalizing behavior in a regular education setting. First- and second-grade students (N = 100) from 38 schools were randomly assigned to either the intervention or an active…

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

ERIC Educational Resources Information Center

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

2014-01-01

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

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2015-09-01

Award Number: W81XWH-09-1-0596 TITLE: A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High...1-0596 A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrat Biochemically Relapsed...in December 2014 with approval to proceed without modifications. 15. SUBJECT TERMS Prostate cancer, PSA, PSMA , monoclonal antibody

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.

Intensive Language Action Therapy in Chronic Aphasia: A Randomized Clinical Trial Examining Guidance by Constraint

PubMed Central

Stanek,, Edward J.; Stokes, Polly; Li, Minming; Andrianopoulos, Mary

2016-01-01

Purpose Intensive language action therapy (ILAT) can be effective in overcoming learned nonuse in chronic aphasia. It is suggested that all three guiding principles (constraint, communication embedding, massed practice) are essential to ILAT's success. We examined whether one of these, guidance by constraint, is critical. Method Twenty-four participants with aphasia (PWAs) were assigned to ILAT or a modified version of promoting aphasic communicative effectiveness (PACE) in a randomized block, single-blind, parallel-group treatment study. Blocking was by severity (mild/moderate, moderate to severe, severe). Both groups received intensive treatment in the context of therapeutic language action games. Whereas the ILAT group was guided toward spoken responses, the PACE group could choose any response modality. Results All participants, whether assigned to ILAT or PACE groups, improved on the primary outcome measure, picture naming. There was a Severity × Treatment interaction, with the largest effects estimated for PWAs with mild/moderate and moderate to severe aphasia. Regardless of severity, the ILAT group outperformed the PACE group on untrained pictures, suggesting some benefit of ILAT to generalization. However, this difference was not statistically significant. Conclusion Although the groups differed in subtle ways, including better generalization to untrained pictures for ILAT, the study was inconclusive on the influence of guidance by constraint. PMID:27997954

Effects of yoga on chronic neck pain: a systematic review of randomized controlled trials

PubMed Central

Kim, Sang-Dol

2016-01-01

[Purpose] The aim of this study was to investigate the effectiveness of yoga in the management of chronic neck pain. [Subjects and Methods] Five electronic databases were searched to identify randomized controlled trials (RCTs) of yoga intervention on chronic neck pain. The trials were published in the English language between January 1966 and December 2015. The Cochrane Risk of Bias Tool was used to assess the quality of the trials. [Results] Three trials were identified and included in this review. A critical appraisal was performed on the trials, and the result indicated a high risk of bias. A narrative description was processed because of the small number of RCTs. Neck pain intensity and functional disability were significantly lower in the yoga groups than in the control groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that yoga may be beneficial for chronic neck pain. The low-quality result of the critical appraisal and the small number of trials suggest that high-quality RCTs are required to examine further the effects of yoga intervention on chronic neck pain relief. PMID:27512290

Description of interventions is under-reported in physical therapy clinical trials.

PubMed

Hariohm, K; Jeyanthi, S; Kumar, J Saravan; Prakash, V

Amongst several barriers to the application of quality clinical evidence and clinical guidelines into routine daily practice, poor description of interventions reported in clinical trials has received less attention. Although some studies have investigated the completeness of descriptions of non-pharmacological interventions in randomized trials, studies that exclusively analyzed physical therapy interventions reported in published trials are scarce. To evaluate the quality of descriptions of interventions in both experimental and control groups in randomized controlled trials published in four core physical therapy journals. We included all randomized controlled trials published from the Physical Therapy Journal, Journal of Physiotherapy, Clinical Rehabilitation, and Archives of Physical Medicine and Rehabilitation between June 2012 and December 2013. Each randomized controlled trial (RCT) was analyzed and coded for description of interventions using the checklist developed by Schroter et al. Out of 100 RCTs selected, only 35 RCTs (35%) fully described the interventions in both the intervention and control groups. Control group interventions were poorly described in the remaining RCTs (65%). Interventions, especially in the control group, are poorly described in the clinical trials published in leading physical therapy journals. A complete description of the intervention in a published report is crucial for physical therapists to be able to use the intervention in clinical practice. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials.

PubMed

Machado, L A C; Kamper, S J; Herbert, R D; Maher, C G; McAuley, J H

2009-05-01

Estimates of treatment effects reported in placebo-controlled randomized trials are less subject to bias than those estimates provided by other study designs. The objective of this meta-analysis was to estimate the analgesic effects of treatments for non-specific low back pain reported in placebo-controlled randomized trials. Medline, Embase, Cinahl, PsychInfo and Cochrane Central Register of Controlled Trials databases were searched for eligible trials from earliest records to November 2006. Continuous pain outcomes were converted to a common 0-100 scale and pooled using a random effects model. A total of 76 trials reporting on 34 treatments were included. Fifty percent of the investigated treatments had statistically significant effects, but for most the effects were small or moderate: 47% had point estimates of effects of <10 points on the 100-point scale, 38% had point estimates from 10 to 20 points and 15% had point estimates of >20 points. Treatments reported to have large effects (>20 points) had been investigated only in a single trial. This meta-analysis revealed that the analgesic effects of many treatments for non-specific low back pain are small and that they do not differ in populations with acute or chronic symptoms.

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review

PubMed Central

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-01-01

Aim Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS). The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials. Method A systematic review of randomized controlled trials was conducted. Only trials that have reported significant FMS-related outcomes were included. Data relating to the components of hydrotherapy programs (exercise type, duration, frequency and intensity, environmental factors, and service delivery) were analyzed. Results Eleven randomized controlled trials were included in this review. Overall, the quality of trials was good. Aerobic exercise featured in all 11 trials and the majority of hydrotherapy programs included either a strengthening or flexibility component. Great variability was noted in both the environmental components of hydrotherapy programs and service delivery. Conclusions Aerobic exercise, warm up and cool-down periods and relaxation exercises are common features of hydrotherapy programs that report significant FMS-related outcomes. Treatment duration of 60 minutes, frequency of three sessions per week and an intensity equivalent to 60%–80% maximum heart rate were the most commonly reported exercise components. Exercise appears to be the most important component of an effective hydrotherapy program for FMS, particularly when considering mental health-related outcomes. PMID:21197303

Randomized Controlled Trials Evaluating Effect of Television Advertising on Food Intake in Children: Why Such a Sensitive Topic is Lacking Top-Level Evidence?

PubMed

Gregori, Dario; Ballali, Simonetta; Vecchio, Maria Gabriella; Sciré, Antonella Silvia; Foltran, Francesca; Berchialla, Paola

2014-01-01

The aim of this study was to perform a systematic review of evidence coming from randomized controlled trials (RCT) aimed at assessing the effect of television advertising on food intake in children from 4 to 12 years old. Randomized controlled trials were searched in PubMed database and included if they assessed the effect of direct exposure to television food advertising over the actual energy intake of children. Seven studies out of 2166 fulfilled the inclusion criteria. The association between television advertising and energy intake is based on a very limited set of randomized researches lacking a solid ground of first-level evidence.

[Realization of design regarding experimental research in the clinical real-world research].

PubMed

He, Q; Shi, J P

2018-04-10

Real world study (RWS), a further verification and supplement for explanatory randomized controlled trial to evaluate the effectiveness of intervention measures in real clinical environment, has increasingly become the focus in the field of research on medical and health care services. However, some people mistakenly equate real world study with observational research, and argue that intervention and randomization cannot be carried out in real world study. In fact, both observational and experimental design are the basic designs in real world study, while the latter usually refers to pragmatic randomized controlled trial and registry-based randomized controlled trial. Other nonrandomized controlled and adaptive designs can also be adopted in the RWS.

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

PubMed

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

2009-11-09

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

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

PubMed Central

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

2009-01-01

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

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

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

PubMed

Al-Kawas, Firas; Aslanian, Harry; Baillie, John; Banovac, Filip; Buscaglia, Jonathan M; Buxbaum, James; Chak, Amitabh; Chong, Bradford; Coté, Gregory A; Draganov, Peter V; Dua, Kulwinder; Durkalski, Valerie; Elmunzer, B Joseph; Foster, Lydia D; Gardner, Timothy B; Geller, Brian S; Jamidar, Priya; Jamil, Laith H; Keswani, Rajesh N; Khashab, Mouen A; Lang, Gabriel D; Law, Ryan; Lichtenstein, David; Lo, Simon K; McCarthy, Sean; Melo, Silvio; Mullady, Daniel; Nieto, Jose; Bayne Selby, J; Singh, Vikesh K; Spitzer, Rebecca L; Strife, Brian; Tarnaksy, Paul; Taylor, Jason R; Tokar, Jeffrey; Wang, Andrew Y; Williams, April; Willingham, Field; Yachimski, Patrick

2018-02-14

The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

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.

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 sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Trial registration Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010). PMID:24919485

Effects of a Psychological Intervention in a Primary Health Care Center for Caregivers of Dependent Relatives: A Randomized Trial

ERIC Educational Resources Information Center

Rodriguez-Sanchez, Emiliano; Patino-Alonso, Maria C.; Mora-Simon, Sara; Gomez-Marcos, Manuel A.; Perez-Penaranda, Anibal; Losada-Baltar, Andres; Garcia-Ortiz, Luis

2013-01-01

Purpose: To assess, in the context of Primary Health Care (PHC), the effect of a psychological intervention in mental health among caregivers (CGs) of dependent relatives. Design and Methods: Randomized multicenter, controlled clinical trial. The 125 CGs included in the trial were receiving health care in PHC. Inclusion criteria: Identifying…

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…

Estimates of Intraclass Correlation Coefficients from Longitudinal Group-Randomized Trials of Adolescent HIV/STI/Pregnancy Prevention Programs

ERIC Educational Resources Information Center

Glassman, Jill R.; Potter, Susan C.; Baumler, Elizabeth R.; Coyle, Karin K.

2015-01-01

Introduction: Group-randomized trials (GRTs) are one of the most rigorous methods for evaluating the effectiveness of group-based health risk prevention programs. Efficiently designing GRTs with a sample size that is sufficient for meeting the trial's power and precision goals while not wasting resources exceeding them requires estimates of the…

Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial.

PubMed

Semler, Matthew W; Self, Wesley H; Wang, Li; Byrne, Daniel W; Wanderer, Jonathan P; Ehrenfeld, Jesse M; Stollings, Joanna L; Kumar, Avinash B; Hernandez, Antonio; Guillamondegui, Oscar D; May, Addison K; Siew, Edward D; Shaw, Andrew D; Bernard, Gordon R; Rice, Todd W

2017-03-16

Saline, the intravenous fluid most commonly administered to critically ill adults, contains a high chloride content, which may be associated with acute kidney injury and death. Whether using balanced crystalloids rather than saline decreases the risk of acute kidney injury and death among critically ill adults remains unknown. The Isotonic Solutions and Major Adverse Renal Events Trial (SMART) is a pragmatic, cluster-level allocation, cluster-level crossover trial being conducted between 1 June 2015 and 30 April 2017 in five intensive care units at Vanderbilt University Medical Center in Nashville, TN, USA. SMART compares saline (0.9% sodium chloride) with balanced crystalloids (clinician's choice of lactated Ringer's solution or Plasma-Lyte A®). Each intensive care unit is assigned to provide either saline or balanced crystalloids each month, with the assigned crystalloid alternating monthly over the course of the trial. All adults admitted to participating intensive care units during the study period are enrolled and followed until hospital discharge or 30 days after enrollment. The anticipated enrollment is approximately 14,000 patients. The primary outcome is Major Adverse Kidney Events within 30 days-the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction (discharge creatinine ≥200% of baseline creatinine). Secondary clinical outcomes include in-hospital mortality, intensive care unit-free days, ventilator-free days, vasopressor-free days, and renal replacement therapy-free days. Secondary renal outcomes include new renal replacement therapy receipt, persistent renal dysfunction, and incidence of stage 2 or higher acute kidney injury. This ongoing pragmatic trial will provide the largest and most comprehensive comparison to date of clinical outcomes with saline versus balanced crystalloids among critically ill adults. For logistical reasons, SMART was prospectively registered separately for the medical ICU (SMART-MED; ClinicalTrials.gov identifier: NCT02444988 ; registered on 11 May 2015; date of first patient enrollment: 1 June 2015) and the nonmedical ICUs (SMART-SURG; ClinicalTrials.gov identifier: NCT02547779 ; registered on 9 September 2015; date of first patient enrollment: 1 October 2015).

Five Year Results of US Intergroup/RTOG 9704 With Postoperative CA 19-9 {<=}90 U/mL and Comparison to the CONKO-001 Trial

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

Berger, Adam C., E-mail: adam.berger@jefferson.edu; Winter, Kathryn; Hoffman, John P.

2012-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of {<=}90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. Methods and Materials: CA 19-9 expression was analyzed as a dichotomized variable ({<=}90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Results: Both univariate (hazardmore » ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of {>=}90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 {>=}90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. Conclusions: This analysis demonstrates that patients with postresection CA 19-9 values {>=}90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).« less

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine

PubMed Central

Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L.; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

2010-01-01

Compared to other specialties, the field of Physical and Rehabilitation Medicine (PRM) has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional PRM treatments. The best way to change this disadvantage is through well-conducted clinical research, such as the standard placebo or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in PRM that ultimately translates in a better clinical care. To address the challenges for the use of placebo in PRM randomized clinical trials, and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in PRM, (2) challenges for the use of placebo in PRM, (3) bioethical issues, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group. PMID:20090428

“Entering a Clinical Trial: Is it Right For You?"-- A Randomized Study of The Clinical Trials Video and Its Impact on the Informed Consent Process

PubMed Central

Hoffner, Brianna; Bauer-Wu, Susan; Hitchcock-Bryan, Suzanne; Powell, Mark; Wolanski, Andrew; Joffe, Steven

2011-01-01

PURPOSE This randomized study was designed to assess the utility of an educational video in preparing cancer patients for decisions about clinical trial participation. The study assessed the effect of the video on patients’ understanding and perceptions of clinical trials, its impact on decision making and patient-provider communication, and patients’ satisfaction with the video. METHODS Ninety adults considering cancer clinical trials were randomized to receive (n=45) or not receive (n=45) the video. Using the validated Quality of Informed Consent (QuIC), respondents’ knowledge about clinical trial participation was assessed. All subjects completed additional questions about satisfaction with the video, decision making, and patient-provider communication. Data were analyzed using the Wilcoxon rank-sum test, regression model and descriptive statistics. RESULTS Although intent-to-treat analysis found no significant group differences in objective understanding between those randomized to view or not view the video, the majority of participants reported favorable experiences with regard to watching the video: 85% found the video was an important source of information about clinical trials; 81% felt better prepared to discuss the trial with their physician; 89% of those who watched the video with family indicated that it helped family better understand clinical trials; and 73% indicated it helped family accept their decision about participation. CONCLUSIONS Although the video did not measurably improve patients’ knowledge about clinical trials, it was an important source of information, helped educate families, and enhanced patient communication with their oncology providers. PMID:22009665

Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial.

PubMed

Matsuoka, Yutaka; Nishi, Daisuke; Yonemoto, Naohiro; Hamazaki, Kei; Matsumura, Kenta; Noguchi, Hiroko; Hashimoto, Kenji; Hamazaki, Tomohito

2013-01-05

Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people. ClinicalTrials.gov Identifier NCT00671099.

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

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 practice.

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

PubMed

Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

2018-05-01

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

Effectiveness of De Qi during acupuncture for the treatment of tinnitus: study protocol for a randomized controlled trial.

PubMed

Xie, Hui; Li, Xinrong; Lai, Jiaqin; Zhou, Yanan; Wang, Caiying; Liang, Jiao

2014-10-15

Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).

Lay public's understanding of equipoise and randomisation in randomised controlled trials.

PubMed

Robinson, E J; Kerr, C E P; Stevens, A J; Lilford, R J; Braunholtz, D A; Edwards, S J; Beck, S R; Rowley, M G

2005-03-01

To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. Healthy adults with a wide range of educational backgrounds and ages. Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.

Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis - an Assessor and Statistician Blinded Randomized Controlled Trial.

PubMed

Schreiber, Sanja; Parent, Eric C; Khodayari Moez, Elham; Hedden, Douglas M; Hill, Douglas L; Moreau, Marc; Lou, Edmond; Watkins, Elise M; Southon, Sarah C

2016-01-01

The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis. To determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS. Fifty patients with AIS aged 10-18 years, with curves of 10°-45° and Risser grade 0-5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30-45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported. In the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5°, 95% CI -1.1° to -5.9°, p = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40°, (95% CI -0.03° to -0.8°, p = 0.046), suggesting that an average patient with 51.2° at baseline, will have a 49.3° Sum of Curves at six months in the Schroth group, and 55.1° in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1° (95% CI -1.7° to -6.5°, p = 0.002) and [Formula: see text] (95% CI -0.8 to 0.2, p = 0.006). Schroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS. NCT01610908.

Reporting funding source or conflict of interest in abstracts of randomized controlled trials, no evidence of a large impact on general practitioners' confidence in conclusions, a three-arm randomized controlled trial.

PubMed

Buffel du Vaure, Céline; Boutron, Isabelle; Perrodeau, Elodie; Ravaud, Philippe

2014-04-28

Systematic reporting of funding sources is recommended in the CONSORT Statement for abstracts. However, no specific recommendation is related to the reporting of conflicts of interest (CoI). The objective was to compare physicians' confidence in the conclusions of abstracts of randomized controlled trials of pharmaceutical treatment indexed in PubMed. We planned a three-arm parallel-group randomized trial. French general practitioners (GPs) were invited to participate and were blinded to the study's aim. We used a representative sample of 75 abstracts of pharmaceutical industry-funded randomized controlled trials published in 2010 and indexed in PubMed. Each abstract was standardized and reported in three formats: 1) no mention of the funding source or CoI; 2) reporting the funding source only; and 3) reporting the funding source and CoI. GPs were randomized according to a computerized randomization on a secure Internet system at a 1:1:1 ratio to assess one abstract among the three formats. The primary outcome was GPs' confidence in the abstract conclusions (0, not at all, to 10, completely confident). The study was planned to detect a large difference with an effect size of 0.5. Between October 2012 and June 2013, among 605 GPs contacted, 354 were randomized, 118 for each type of abstract. The mean difference (95% confidence interval) in GPs' confidence in abstract findings was 0.2 (-0.6; 1.0) (P = 0.84) for abstracts reporting the funding source only versus no funding source or CoI; -0.4 (-1.3; 0.4) (P = 0.39) for abstracts reporting the funding source and CoI versus no funding source and CoI; and -0.6 (-1.5; 0.2) (P = 0.15) for abstracts reporting the funding source and CoI versus the funding source only. We found no evidence of a large impact of trial report abstracts mentioning funding sources or CoI on GPs' confidence in the conclusions of the abstracts. ClinicalTrials.gov identifier: NCT01679873.

Rationale of a novel study design for the BIOFLOW V study, a prospective, randomized multicenter study to assess the safety and efficacy of the Orsiro sirolimus-eluting coronary stent system using a Bayesian approach.

PubMed

Doros, Gheorghe; Massaro, Joseph M; Kandzari, David E; Waksman, Ron; Koolen, Jacques J; Cutlip, Donald E; Mauri, Laura

2017-11-01

Traditional study design submitted to the Food and Drug Administration to test newer drug-eluting stents (DES) for marketing approval is the prospective randomized controlled trial. However, several DES have extensive clinical data from trials conducted outside the United States that have led to utilization of a novel design using the Bayesian approach. This design was proposed for testing DES with bioresorbable polymer compared with DES most commonly in use today that use durable polymers for drug elution. This prospective, multicenter, randomized, controlled trial is designed to assess the safety and efficacy of the Orsiro bioresorbable polymer sirolimus-eluting stent (BP SES). Up to 1,334 subjects with up to 3 de novo or restenotic coronary artery lesions who qualify for percutaneous coronary intervention with stenting will be randomized 2:1 to the BP SES versus the Xience durable polymer everolimus-eluting stent (DP EES). Data from this trial will be combined with data from 2 similarly designed trials that also randomize subjects to BP SES and DP EES (BIOFLOW II, N=452 and BIOFLOW IV, N=579) by using a Bayesian approach. The primary end point is target lesion failure at 12 months post index procedure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization, and the primary analysis is a test of noninferiority of the BP SES versus DP EES on the primary end point according to a noninferiority delta of 3.85%. Secondary end points include stent thrombosis and the individual components of target lesion failure. Subjects will be followed for 5 years after randomization. The BIOFLOW V trial offers an opportunity to assess clinical outcomes in patients treated with coronary revascularization using the Orsiro BP SES relative to a commonly used DP EES. The use of a Bayesian analysis combines a large randomized cohort of patients 2 two smaller contributing randomized trials to augment the efficiency of the comparison. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and implementation of a dental caries prevention trial in remote Canadian Aboriginal communities

PubMed Central

2010-01-01

Background The goal of this cluster randomized trial is to test the effectiveness of a counseling approach, Motivational Interviewing, to control dental caries in young Aboriginal children. Motivational Interviewing, a client-centred, directive counseling style, has not yet been evaluated as an approach for promotion of behaviour change in indigenous communities in remote settings. Methods/design Aboriginal women were hired from the 9 communities to recruit expectant and new mothers to the trial, administer questionnaires and deliver the counseling to mothers in the test communities. The goal is for mothers to receive the intervention during pregnancy and at their child's immunization visits. Data on children's dental health status and family dental health practices will be collected when children are 30-months of age. The communities were randomly allocated to test or control group by a random "draw" over community radio. Sample size and power were determined based on an anticipated 20% reduction in caries prevalence. Randomization checks were conducted between groups. Discussion In the 5 test and 4 control communities, 272 of the original target sample size of 309 mothers have been recruited over a two-and-a-half year period. A power calculation using the actual attained sample size showed power to be 79% to detect a treatment effect. If an attrition fraction of 4% per year is maintained, power will remain at 80%. Power will still be > 90% to detect a 25% reduction in caries prevalence. The distribution of most baseline variables was similar for the two randomized groups of mothers. However, despite the random assignment of communities to treatment conditions, group differences exist for stage of pregnancy and prior tooth extractions in the family. Because of the group imbalances on certain variables, control of baseline variables will be done in the analyses of treatment effects. This paper explains the challenges of conducting randomized trials in remote settings, the importance of thorough community collaboration, and also illustrates the likelihood that some baseline variables that may be clinically important will be unevenly split in group-randomized trials when the number of groups is small. Trial registration This trial is registered as ISRCTN41467632. PMID:20465831

Sleep-Disordered Breathing in Chronic SCI: A Randomized Controlled Trial of Treatment Impact on Cognition, Quality of Life, and Cardiovascular Disease

DTIC Science & Technology

2014-10-01

SCI. In this prospective randomized controlled trial, we will objectively measure sleep disordered breathing ( SDB ) in chronic SCI patients using...portable sleep studies, and systematically evaluate the association between SDB , cognitive performance, mood, pain, and CV measures. We will randomize...randomized shortly. 15. SUBJECT TERMS SDB , SCI, PAP, CV 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a

Effect of Art Production on Negative Mood: A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Bell, Chloe E.; Robbins, Steven J.

2007-01-01

Art therapists have long held that art production causes reductions in stress and elevations in mood (Rubin, 1999). The authors examined this claim in a randomized, controlled trial. Fifty adults between the ages of 18 and 30 were randomly assigned to either create an art work or to view and sort a series of art prints. Three measures of overall…

A Cluster Randomized Controlled Trial Testing the Effectiveness of Houvast: A Strengths-Based Intervention for Homeless Young Adults

ERIC Educational Resources Information Center

Krabbenborg, Manon A. M.; Boersma, Sandra N.; van der Veld, William M.; van Hulst, Bente; Vollebergh, Wilma A. M.; Wolf, Judith R. L. M.

2017-01-01

Objective: To test the effectiveness of Houvast: a strengths-based intervention for homeless young adults. Method: A cluster randomized controlled trial was conducted with 10 Dutch shelter facilities randomly allocated to an intervention and a control group. Homeless young adults were interviewed when entering the facility and when care ended.…

A Randomized Clinical Trial of Cognitive-Behavioral Treatment for PTSD in Women

DTIC Science & Technology

2004-10-01

This study is a randomized clinical trial comparing two types of individual psychotherapy for treating PTSD in 384 female veterans and active duty...Exposure therapy will be more effective than Present Centered Therapy for the treatment of PTSD in female veterans and active duty personnel. The study has entered the randomized phase. There are no conclusions to date.

Understanding Statistical Power in Cluster Randomized Trials: Challenges Posed by Differences in Notation and Terminology

ERIC Educational Resources Information Center

Spybrook, Jessaca; Hedges, Larry; Borenstein, Michael

2014-01-01

Research designs in which clusters are the unit of randomization are quite common in the social sciences. Given the multilevel nature of these studies, the power analyses for these studies are more complex than in a simple individually randomized trial. Tools are now available to help researchers conduct power analyses for cluster randomized…

What to Do when Data Are Missing in Group Randomized Controlled Trials. NCEE 2009-0049

ERIC Educational Resources Information Center

Puma, Michael J.; Olsen, Robert B.; Bell, Stephen H.; Price, Cristofer

2009-01-01

This NCEE Technical Methods report examines how to address the problem of missing data in the analysis of data in Randomized Controlled Trials (RCTs) of educational interventions, with a particular focus on the common educational situation in which groups of students such as entire classrooms or schools are randomized. Missing outcome data are a…

The Effects of School Gardens on Children's Science Knowledge: A Randomized Controlled Trial of Low-Income Elementary Schools

ERIC Educational Resources Information Center

Wells, Nancy M.; Myers, Beth M.; Todd, Lauren E.; Barale, Karen; Gaolach, Brad; Ferenz, Gretchen; Aitken, Martha; Henderson, Charles R.; Tse, Caroline; Pattison, Karen Ostlie; Taylor, Cayla; Connerly, Laura; Carson, Janet B.; Gensemer, Alexandra Z.; Franz, Nancy K.; Falk, Elizabeth

2015-01-01

This randomized controlled trial or "true experiment" examines the effects of a school garden intervention on the science knowledge of elementary school children. Schools were randomly assigned to a group that received the garden intervention (n?=?25) or to a waitlist control group that received the garden intervention at the end of the…

The Ecological Effects of Universal and Selective Violence Prevention Programs for Middle School Students: A Randomized Trial

ERIC Educational Resources Information Center

Simon, Thomas R.; Ikeda, Robin M.; Smith, Emilie Phillips; Reese, Le'Roy E.; Rabiner, David L.; Miller, Shari; Winn, Donna-Marie; Dodge, Kenneth A.; Asher, Steven R.; Horne, Arthur M.; Orpinas, Pamela; Martin, Roy; Quinn, William H.; Tolan, Patrick H.; Gorman-Smith, Deborah; Henry, David B.; Gay, Franklin N.; Schoeny, Michael; Farrell, Albert D.; Meyer, Aleta L.; Sullivan, Terri N.; Allison, Kevin W.

2009-01-01

This study reports the findings of a multisite randomized trial evaluating the separate and combined effects of 2 school-based approaches to reduce violence among early adolescents. A total of 37 schools at 4 sites were randomized to 4 conditions: (1) a universal intervention that involved implementing a student curriculum and teacher training…

A Randomized Controlled Trial of Two Syntactic Treatment Procedures with Cantonese-Speaking, School-Age Children with Language Disorders

ERIC Educational Resources Information Center

To, Carol K. S.; Lui, Hoi Ming; Li, Xin Xin; Lam, Gary Y. H

2015-01-01

Purpose: In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Method: Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment…

Mechanism of Developmental Change in the PLAY Project Home Consultation Program: Evidence from a Randomized Control Trial

ERIC Educational Resources Information Center

Mahoney, Gerald; Solomon, Richard

2016-01-01

This investigation is a secondary analysis of data from a randomized control trial of the PLAY Home Consultation Intervention Program which was conducted with 112 preschool children with Autism Spectrum Disorders and their parents (Solomon et al. in "J Dev Behav Pediatr" 35:475-485, 2014). Subjects were randomly assigned to either a…

A Randomized Prospective Trial Comparing Paravertebral Block and General Anesthesia for Operative Treatment of Breast Cancer

DTIC Science & Technology

2001-10-01

block the anesthetic of choice for operative treatment of breast cancer. To test this hypothesis we proposed a prospective randomized clinical trial ...coordinators. Months 4-6. Status: Complete The study’s existing part-time Clinical Trial Coordinator, Mr. John Arbo, was enlisted full-time in June...of full-time Clinical Trial Coordinator for Mount Sinai. ■ Poster presentation by Mount Sinai staff of study goals and methods at a Department of

5-Year Safety and Efficacy of Resolute Zotarolimus-Eluting Stent: The RESOLUTE Global Clinical Trial Program.

PubMed

Yeh, Robert W; Silber, Sigmund; Chen, Lianglong; Chen, Shaoliang; Hiremath, Shirish; Neumann, Franz-Josef; Qiao, Shubin; Saito, Shigeru; Xu, Bo; Yang, Yuejin; Mauri, Laura

2017-02-13

The authors evaluated the 5-year cumulative incidence of cardiovascular events following Resolute zotarolimus-eluting stent (R-ZES) implantation. Individual trials are often underpowered to show differences for low-frequency adverse events. The R-ZES was studied in 10 prospective clinical trials, designed with identical adverse event definitions, ascertainment, and adjudication. The RESOLUTE Global Clinical Trial Program includes 7,618 patients treated with R-ZES: RESOLUTE first-in-human study (N = 139), RESOLUTE All Comers (N = 1,140), RESOLUTE International (N = 2,349), RESOLUTE US (N = 1,402), RESOLUTE US 38 mm (N = 114), RESOLUTE Japan (N = 100), RESOLUTE Japan Small Vessel Study (N = 65), RESOLUTE Asia (N = 311), RESOLUTE China Randomized Controlled Trial (N = 198), and RESOLUTE China Registry (N = 1,800). The 5-year cumulative incidence of events was calculated. The 5-year cumulative incidence of cardiac events was 13.4% for target lesion failure and included 5.0% cardiac death, 4.4% target vessel myocardial infarction, and 6.3% clinically driven target lesion revascularization. Dual-antiplatelet therapy at 1, 3, and 5 years was 91%, 37%, and 32%, respectively. The 5-year cumulative incidence of definite or probable stent thrombosis was 1.2%, which comprised 0.7% at 1 year and an annualized rate of 0.1% thereafter. Five-year use of dual-antiplatelet therapy varied geographically from 63% in Japan to 11% in Europe. In the largest group of R-ZES patients examined to date, the majority of stent-related events, including target vessel myocardial infarction and stent thrombosis, occurred within the first year of implantation with much lower risks of these events out to 5 years. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effects of free sugars on blood pressure and lipids: a systematic review and meta-analysis of nutritional isoenergetic intervention trials.

PubMed

Fattore, Elena; Botta, Francesca; Agostoni, Carlo; Bosetti, Cristina

2017-01-01

Sugar has been suggested as a central risk factor in the development of noncommunicable diseases. We assessed the evidence of the effects of free sugars compared with complex carbohydrates on selected cardiovascular disease risk factors. We conducted a systematic review and meta-analysis of intervention trials to compare diets that provide a given amount of energy from free sugars with a control diet that provides the same amount of energy from complex carbohydrates. The primary outcomes were: blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triacylglycerols, apolipoproteins A-I and B, or very low-density lipoprotein cholesterol. Body weight was also recorded but was not a primary outcome of the studies. In all, 28 studies involving 510 volunteers were included. When free sugars were substituted for complex carbohydrates, no significant increases were detected in systolic or diastolic blood pressure, and no heterogeneity was observed. There were significant increases in HDL cholesterol, LDL cholesterol, and triacylglycerols, although for LDL cholesterol and triacylglycerols there was significant heterogeneity between studies and evidence of publication bias. After adjustment for missing studies, these increases lost significance. Subgroup analyses showed that diets providing the largest total energy intake and energy exchange enhanced the effect of free sugars on total and LDL cholesterol and triacylglycerols. The increase of triacylglycerols was no longer significant when studies with the highest risk of bias were excluded or when only randomized trials were considered. Free sugars had no effect on body weight. In short- or moderate-term isoenergetic intervention trials, the substitution of free sugars for complex carbohydrates had no effect on blood pressure or body weight and an unclear effect on blood lipid profile. Further independent trials are required to assess whether the reduction of free sugars improves cardiovascular disease risk factors. This review was registered at http://www.crd.york.ac.uk/prospero as CRD42016042930. © 2017 American Society for Nutrition.

Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

PubMed Central

Murray, Elizabeth; Kalaitzaki, Eleftheria; White, Ian R; McCambridge, Jim; Thompson, Simon G; Wallace, Paul; Godfrey, Christine

2011-01-01

Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2. Conclusion Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration. Trial registration ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s) PMID:21371988

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 retrieved by this search but there was insufficient information in the title and abstract to code these as trials. The EMBASE records for the remaining 5 reports of trials did not contain terms currently used by The Cochrane Collaboration to identify reports of randomized trials in this database. The handsearching of these journals will help minimize publication bias by locating randomized trials not previously identified and, through their inclusion in the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, will ensure reports of randomized trials will not remain buried through indexing bias.

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

PubMed

Gulliford, Martin C; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Charlton, Judith; Dregan, Alex

2014-06-11

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). 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. 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. 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 sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010).

New directions in behavioral treatment of autism spectrum disorders

PubMed Central

Kasari, Connie; Lawton, Kathy

2014-01-01

Purpose of review The review explores current trends in the behavioral intervention literature for children with an autism spectrum disorder (ASD) during 2008 and 2009. Noteworthy findings and intervention strategies are highlighted. Additionally, the quality of all reviewed studies is systematically evaluated. Recent findings During 2008 and 2009, there was nearly a quarter increase in the number of behavioral intervention studies, as well as more randomized controlled trials and approaches other than applied behavior analysis. Many of the studies investigated commonly used ASD intervention practices or novel treatments. A few were conducted with underserved populations, such as toddlers and adults with ASD. Social impairment was the focus of the largest number of intervention studies. A small percentage of studies were rated as high-quality. Summary Overall, the reviewed studies suggest that ASD-specific deficits can be improved through behavioral intervention. However, whereas progress continues to be made in our understanding of effective treatments for children with ASD, confidence in these findings would be improved with higher-quality studies. PMID:20160648

Are cannabinoids an effective treatment for chronic non-cancer pain?

PubMed

Allende-Salazar, Rubén F; Rada, Gabriel

2017-06-14

The use of cannabinoids has been proposed as an analgesic for different painful conditions, especially for chronic pain refractory to usual treatment. However, its real efficacy and safety remains controversial. We sought to determine whether cannabinoids are an effective treatment for chronic non-cancer pain. To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We identified 37 systematic reviews including 41 studies overall, of which 32 were randomized trials relevant for the question of interest. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether cannabinoids decrease pain in patients with chronic non-cancer pain because the certainty of available evidence is very low. On the other hand, they are associated with significant adverse effects.

Preference option randomized design (PORD) for comparative effectiveness research: Statistical power for testing comparative effect, preference effect, selection effect, intent-to-treat effect, and overall effect.

PubMed

Heo, Moonseong; Meissner, Paul; Litwin, Alain H; Arnsten, Julia H; McKee, M Diane; Karasz, Alison; McKinley, Paula; Rehm, Colin D; Chambers, Earle C; Yeh, Ming-Chin; Wylie-Rosett, Judith

2017-01-01

Comparative effectiveness research trials in real-world settings may require participants to choose between preferred intervention options. A randomized clinical trial with parallel experimental and control arms is straightforward and regarded as a gold standard design, but by design it forces and anticipates the participants to comply with a randomly assigned intervention regardless of their preference. Therefore, the randomized clinical trial may impose impractical limitations when planning comparative effectiveness research trials. To accommodate participants' preference if they are expressed, and to maintain randomization, we propose an alternative design that allows participants' preference after randomization, which we call a "preference option randomized design (PORD)". In contrast to other preference designs, which ask whether or not participants consent to the assigned intervention after randomization, the crucial feature of preference option randomized design is its unique informed consent process before randomization. Specifically, the preference option randomized design consent process informs participants that they can opt out and switch to the other intervention only if after randomization they actively express the desire to do so. Participants who do not independently express explicit alternate preference or assent to the randomly assigned intervention are considered to not have an alternate preference. In sum, preference option randomized design intends to maximize retention, minimize possibility of forced assignment for any participants, and to maintain randomization by allowing participants with no or equal preference to represent random assignments. This design scheme enables to define five effects that are interconnected with each other through common design parameters-comparative, preference, selection, intent-to-treat, and overall/as-treated-to collectively guide decision making between interventions. Statistical power functions for testing all these effects are derived, and simulations verified the validity of the power functions under normal and binomial distributions.

Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.

PubMed

Wagenlehner, Florian M E; van Till, J W Olivier; Houbiers, Jos G A; Martina, Reynaldo V; Cerneus, Dirk P; Melis, Joost H J M; Majek, Antoni; Vjaters, Egils; Urban, Michael; Ramonas, Henrikas; Shoskes, Daniel A; Nickel, J Curtis

2017-05-01

To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors. In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions, and analysis of the efficacy variables. The study was stopped for futility at preplanned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25 mg group showed the largest reduction of the primary end point National Institutes of Health Chronic Prostatitis Symptom Index total score (7.0 points), but the placebo group showed a mean reduction of 7.3 points (difference: 0.3 [95% confidence interval: -1.9, 2.6]). Micturition outcomes improved compared with placebo in all ASP3652 groups; for example, in the 300 mg twice daily group, voiding frequency decreased by -1.10 (95% CI: -2.0, -0.2) voids/24 hours vs placebo. Safety outcomes were comparable across the treatment groups. ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, the results indicate that FAAH inhibition may attenuate lower urinary tract symptoms. Dedicated studies in patients with lower urinary tract dysfunction are needed to confirm this. Copyright © 2017 Elsevier Inc. All rights reserved.

Cluster Randomized Test-Negative Design (CR-TND) Trials: A Novel and Efficient Method to Assess the Efficacy of Community Level Dengue Interventions.

PubMed

Anders, Katherine L; Cutcher, Zoe; Kleinschmidt, Immo; Donnelly, Christl A; Ferguson, Neil M; Indriani, Citra; O'Neill, Scott L; Jewell, Nicholas P; Simmons, Cameron P

2018-05-07

Cluster randomized trials are the gold standard for assessing efficacy of community-level interventions, such as vector control strategies against dengue. We describe a novel cluster randomized trial methodology with a test-negative design, which offers advantages over traditional approaches. It utilizes outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest, who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing. We use simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. This demonstrates that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. We also briefly discuss analytical considerations for an odds ratio-based effect estimate arising from clustered data, and outline potential approaches to analysis. We conclude that application of the test-negative design to certain cluster randomized trials could increase their efficiency and ease of implementation.

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.

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.