External validity is an important parameter that needs to be considered for decision making in health research, but no widely accepted measurement tool for the assessment of external validity of randomized controlled trials (RCTs) exists. One of the most limiting factors for creating such a tool is probably the substantial heterogeneity and lack…

Increasing integrity concerns in medical research have prompted the development of tools to detect untrustworthy studies. Existing tools primarily assess published aggregate data (AD), though scrutiny of individual participant data (IPD) is often required to detect trustworthiness issues. Thus, we developed the IPD Integrity Tool for detecting…

Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two-stage network meta-regression prediction model that synthesized randomized trials and evaluates how treatment effects vary across patient characteristics. In this article, we extended this model to combine different…

Outputs from living evidence syntheses projects have been used widely during the pandemic by guideline developers to form evidence-based recommendations. However, the needs of different stakeholders cannot be accommodated by solely providing pre-defined non amendable numerical summaries. Stakeholders also need to understand the data and perform…

Using the Hartung-Knapp method and 95% prediction intervals (PIs) in random-effects meta-analyses is recommended by experts but rarely applied. Therefore, we aimed to reevaluate statistically significant meta-analyses using the Hartung-Knapp method and 95% PIs. In this methodological study, three databases were searched from January 2010 to July…

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…

Background: There is an agreement that the methodological quality of randomized trials should be assessed in systematic reviews, but there is a debate on how this should be done. We conducted a construct validation study of the Physiotherapy Evidence Database (PEDro) scale, which is widely used to assess the quality of trials in physical therapy…