A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Fecal incontinence: the quality of reported randomized, controlled trials in the last ten years.

This study was designed to analyze the characteristics and the quality of reporting of randomized, controlled trials published during the last ten years on fecal incontinence

How necessary are randomized controlled trials?

Randomized controlled trials (RCTs) are often deemed the gold standard for testing new treatments. This belief in turn justifies recruiting patients into such trials even when it is suspected that a new treatment is superior – although patients in the control group are thereby denied what might be the better treatment, we cannot know that the treatment actually is better, the thought runs, without conducting an RCT. But Robert Northcott argues that RCTs are not always the best choice after all. Rather, like any other method, they can go wrong sometimes, in several different ways. The main alternative to them is historical studies, which try to assess a treatment’s effectiveness from data not drawn from trials. These too can go wrong in several ways, and in the past have acquired a bad reputation. However, that prejudice has become outdated. The truer picture, Northcott argues, is that sometimes one method is preferable, sometimes the other. Things must be decided case by case. It follows that the ethical ramifications of conducting an RCT also must be examined case by case; there is no one-size-fits-all answer. An especially striking and emotional example concerns ECMO, a treatment for newborn babies with life-threatening lung problems. Historical studies indicated that ECMO was a major breakthrough, offering hugely increased survival rates. But it was still insisted that it also be tested in RCTs, in the course of which many babies receiving the conventional treatment died. A properly nuanced view of RCTs suggests that these deaths were tragically unnecessary

How can I improve patient adherence to prescribed medication?

Two randomized clinical trials have shown that simplified dosing schedules have improved patient adherence to medication as prescribed. Some, but not all, randomized controlled trials show multidimensional interventions can also improve adherence. These interventions include combinations of patient and family education, home monitoring of disease status, and increased convenience of care, such as workplace access. (Grade of Recommendation: B, based on randomized controlled trials

Stratification Trees for Adaptive Randomization in Randomized Controlled Trials

This paper proposes an adaptive randomization procedure for two-stage randomized controlled trials. The method uses data from a first-wave experiment in order to determine how to stratify in a second wave of the experiment, where the objective is to minimize the variance of an estimator for the average treatment effect (ATE). We consider selection from a class of stratified randomization procedures which we call stratification trees: these are procedures whose strata can be represented as decision trees, with differing treatment assignment probabilities across strata. By using the first wave to estimate a stratification tree, we simultaneously select which covariates to use for stratification, how to stratify over these covariates, as well as the assignment probabilities within these strata. Our main result shows that using this randomization procedure with an appropriate estimator results in an asymptotic variance which is minimal in the class of stratification trees. Moreover, the results we present are able to accommodate a large class of assignment mechanisms within strata, including stratified block randomization. In a simulation study, we find that our method, paired with an appropriate cross-validation procedure ,can improve on ad-hoc choices of stratification. We conclude by applying our method to the study in Karlan and Wood (2017), where we estimate stratification trees using the first wave of their experiment

Why Government Needs More Randomized Controlled Trials: Refuting The Myths

The Laura and John Arnold Foundation (LJAF) today released a policy brief focused on the value and benefits of randomized controlled trials (RCTs). Such trials are widely recognized as the gold standard in scientific research. However, some critics have claimed that they are often expensive, time-consuming, unethical, or not worth the trouble. These objections are almost always overstated or false. In this brief LJAF Vice President of Research Integrity Stuart Buck and LJAF Vice President of Public Accountability Josh McGee explain why RCTs are so valuable, why they are sometimes misunderstood, and why many common objections should be given little weight.The brief addresses seven specific myths about RCTs:RCTs are expensive and slowRCTs are often unethicalRCTs are limited to narrow contexts or questionsRCTs are a black boxRCTs are not suited to complex, fast-changing programsRCTs can still be biasedRCTs are too limitedBy clarifying the value and importance of rigorous evaluation, LJAF aims to help governments use evidence to inform policies and programs that produce meaningful improvements in people's lives

Single versus two-stent strategies for coronary bifurcation lesions: a systematic review and meta-analysis of randomized trials with long-term follow-up

Background: The majority of coronary bifurcation lesions are treated with a provisional single‐stent strategy rather than an up‐front 2‐stent strategy. This approach is supported by multiple randomized controlled clinical trials with short‐ to medium‐term follow‐up; however, long‐term follow‐up data is evolving from many data sets. Methods and Results: Meta‐analysis of randomized controlled trials evaluating long‐term outcomes (≥1 year) according to treatment strategy for coronary bifurcation lesions. Nine randomized controlled trials with 3265 patients reported long‐term clinical outcomes at mean weighted follow‐up of 3.1±1.8 years. Provisional single stenting was associated with lower all‐cause mortality (2.94% versus 4.23%; risk ratio: 0.69; 95% confidence interval, 0.48–1.00; P=0.049; I2=0). There was no difference in major adverse cardiac events (15.8% versus 15.4%; P=0.79), myocardial infarction (4.8% versus 5.5%; P=0.51), target lesion revascularization (9.3% versus 7.6%; P=0.19), or stent thrombosis (1.8% versus 1.6%; P=0.28) between the groups. Prespecified sensitivity analysis of long‐term mortality at a mean of 4.7 years of follow‐up showed that the provisional single‐stent strategy was associated with reduced all‐cause mortality (3.9% versus 6.2%; risk ratio: 0.63; 95% confidence interval, 0.42–0.97; P=0.036; I2=0). Conclusions: Coronary bifurcation percutaneous coronary intervention using a provisional single‐stent strategy is associated with a reduction in all‐cause mortality at long‐term follow‐up

Do antiarrhythmics prevent sudden death in patients with heart failure?

Beta-blockers (class II antiarrhythmics) reduce sudden death and total mortality in patients with heart failure (strength of recommendation [SOR]: A, based on systematic reviews of randomized controlled trials). Amiodarone (class III) may reduce sudden death in heart failure (SOR: B, extrapolation from randomized controlled trials), but evidence is weak that it reduces total mortality, and it has significant side effects. Class I and other class III antiarrhythmic agents appear cause an increase in mortality due to sudden death in heart failure (SOR: B, extrapolations from randomized controlled trials)

Performance of mesenchymal cell-scaffold constructs in human oral reconstructive surgery: a systematic review

Background: Different sources of cultured cells combined with different scaffolds (allogenic, xenogeneic, alloplastic or composite materials) have been tested extensively in vitro and in preclinical animal studies, but there have been only a few clinical trials involving humans. Aim: This study reviewed all of the English language literature published between January 1990 and December 2015 to assess the histological performance of different mesenchymal cell-scaffold constructs used for bone regeneration in human oral reconstructive procedures. Methods: An electronic search of the MEDLINE and Cochrane Central Register of Controlled Trials databases complemented by manual searching was conducted to identify studies involving histological evaluation of mesenchymal cell-scaffold constructs in human oral surgical procedures. The methodological quality of randomized controlled clinical trials and controlled clinical trials was assessed using the Cochrane Collaboration tool for assessing the risk of bias. Heterogeneity was assessed using Review Manager software. Considering the heterogeneity, the data collected were reported by descriptive methods and a meta-analysis was applied only to the articles that reported the same outcome measures. The articles were classified and described based on the material scaffolds used. Results: The search identified 1030 titles and 287 abstracts. Full-text analysis was performed for 32 articles, revealing 14 studies that fulfilled the inclusion criteria. Three randomized controlled clinical trials were identified as potentially eligible for inclusion in a meta-analysis. The studies were grouped according to the scaffold materials used: bone allograft (three studies), polyglycolic-polylactic scaffold (four studies), collagen sponge (two studies), and bovine bone matrix (five studies). The stem cells used in these studies had been sourced from the iliac crest, periosteum, dental pulp and intraoral sites. Conclusions: The very small amount of available data makes it impossible to draw any firm conclusions regarding the increase in bone formation in human oral reconstructive procedures when using graft materials engineered with autogenous stem cells

Matching on-the-fly in Sequential Experiments for Higher Power and Efficiency

We propose a dynamic allocation procedure that increases power and efficiency when measuring an average treatment effect in sequential randomized trials. Subjects arrive iteratively and are either randomized or paired via a matching criterion to a previously randomized subject and administered the alternate treatment. We develop estimators for the average treatment effect that combine information from both the matched pairs and unmatched subjects as well as an exact test. Simulations illustrate the method's higher efficiency and power over competing allocation procedures in both controlled scenarios and historical experimental data.Comment: 20 pages, 1 algorithm, 2 figures, 8 table