Population-adjusted indirect comparisons, developed in the 2010s, enable comparisons between two treatments in different studies by balancing patient characteristics in the case where individual patient-level data (IPD) are available for only one study. Health technology assessment (HTA) bodies increasingly rely on these methods to inform funding…

A substantial proportion of trial registrations are not linked to corresponding published articles, limiting analyses and new tools. Our aim was to develop a method for finding articles reporting the results of trials that are registered on ClinicalTrials.gov when they do not include metadata links. We used a set of 27,280 trial registration and…

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…

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…

Meta-analysis of individual participant data (IPD) is considered the "gold-standard" for synthesizing clinical study evidence. However, gaining access to IPD can be a laborious task (if possible at all) and in practice only summary (aggregate) data are commonly available. In this work we focus on meta-analytic approaches of comparative…

Network meta-analysis has been gaining prominence as an evidence synthesis method that enables the comprehensive synthesis and simultaneous comparison of multiple treatments. In many network meta-analyses, some of the constituent studies may have markedly different characteristics from the others, and may be influential enough to change the…

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…

Background: Model-based meta-analysis (MBMA) is increasingly used to inform drug-development decisions by synthesising results from multiple studies to estimate treatment, dose-response, and time-course characteristics. Network meta-analysis (NMA) is used in Health Technology Appraisals for simultaneously comparing effects of multiple treatments,…

If IPD is available for some or all trials in a network meta-analysis (NMA), then incorporating this IPD into an NMA is routinely considered to be preferable. However, the situation often arises where a researcher has IPD for trials concerning a particular treatment (eg, from a sponsor) but none for other trials. Therefore, one can reweight the…

A network meta-analysis allows a simultaneous comparison between treatments evaluated in randomised controlled trials that share at least one treatment with at least one other study. Estimates of treatment effects may be required for treatments across disconnected networks of evidence, which requires a different statistical approach and modelling…

Indirect treatment comparisons are useful to estimate relative treatment effects when head-to-head studies are not conducted. Statisticians at the National Centre for Pharmacoeconomics Ireland (NCPE) and Scottish Medicines Consortium (SMC) assess the clinical and cost-effectiveness of new medicines as part of multidisciplinary teams. We describe…

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.…

Small-study effects are a common threat in systematic reviews and may indicate publication bias. Their existence is often verified by visual inspection of the funnel plot. Formal tests to assess the presence of funnel plot asymmetry typically estimate the association between the reported effect size and their standard error, the total sample size,…

Background: Many reviews aim to compare numerous treatments and report results stratified by subgroups (eg, by disease severity). In such cases, a network meta-analysis model including treatment by covariate interactions can estimate the relative effects of all treatment pairings for each subgroup of patients. Two key assumptions underlie such…