Introduction: Registration of clinical trials has been initiated in order to assess adherence of the reported results to the original trial protocol. This study aimed to investigate the publication rates, timely dissemination of results, and the prevalence of consistency in hypothesis, sample size, and primary endpoint of Dutch…

During drug development, a biomarker is sometimes identified as separating a patient population into those with more and those with less benefit from evaluated treatments. Consequently, later studies might be targeted, while earlier ones are performed in mixed patient populations. This poses a challenge in evidence synthesis, especially if only…

Indirect comparisons are used to obtain estimates of relative effectiveness between two treatments that have not been compared in the same randomized controlled trial, but have instead been compared against a common comparator in separate trials. Standard indirect comparisons use only aggregate data, under the assumption that there are no…

Randomised trials are often funded by commercial companies and methodological studies support a widely held suspicion that commercial funding may influence trial results and conclusions. However, these studies often have a risk of confounding and reporting bias. The risk of confounding is markedly reduced in meta-epidemiological studies that…

Network meta-analysis is a popular method to synthesize the information obtained in a systematic review of studies (e.g., randomized clinical trials) involving subsets of multiple treatments of interest. The dominant method of analysis employs within-study information on treatment contrasts and integrates this over a network of studies. One…

Many randomized trials evaluate an intervention effect on time-to-event outcomes. Individual participant data (IPD) from such trials can be obtained and combined in a so-called IPD meta-analysis (IPD-MA), to summarize the overall intervention effect. We performed a narrative literature review to provide an overview of methods for conducting an…

Time-course model-based network meta-analysis (MBNMA) has been proposed as a framework to combine treatment comparisons from a network of randomized controlled trials reporting outcomes at multiple time-points. This can explain heterogeneity/inconsistency that arises by pooling studies with different follow-up times and allow inclusion of studies…

Randomized clinical trials underpin evidence-based clinical practice, but flaws in their conduct may lead to biased estimates of intervention effects and hence invalid treatment recommendations. The main approach to the empirical study of bias is to collate a number of meta-analyses and, within each, compare the results of trials with and without…

Background: It has been reported that information sources searched in systematic reviews (SRs) are insufficiently comprehensive. We analyzed information sources used in SRs, as well as how up-to-date were the searches. Methods: We searched PubMed and the Cochrane Database of Systematic Reviews (CDSR) through Wiley from 2012 to 2016 to find SRs of…

Objective: Various statistical methods have been developed to estimate hazard ratios (HRs) from published Kaplan-Meier (KM) curves for the purpose of performing meta-analyses. The objective of this study was to determine the reliability, accuracy, and precision of four commonly used methods by Guyot, Williamson, Parmar, and Hoyle and Henley.…

Researchers may have multiple motivations for combining disparate pieces of evidence in a meta-analysis, such as generalizing experimental results or increasing the power to detect an effect that a single study is not able to detect. However, while in meta-analysis, the main question may be simple, the structure of evidence available to answer it…

The sharp regression discontinuity design (RDD) has three key weaknesses compared to the randomized clinical trial (RCT). It has lower statistical power, it is more dependent on statistical modeling assumptions, and its treatment effect estimates are limited to the narrow subpopulation of cases immediately around the cutoff, which is rarely of…