Importance Unmeasured confounding is a key concern for decision-makers when observational datasets are used to assemble external control arms (ECAs) for single-arm trials. Objective To investigate the utility of quantitative bias analysis (QBA) for exploring the sensitivity to unmeasured confounding of nonrandomized analyses using ECAs. Design, Setting, and Participants This study emulated 15 treatment comparisons using experimental arms from existing randomized trials in advanced non–small cell lung cancer (aNSCL…

APPRAISE is a tool to guide bias assessment in observational studies on medication comparative effectiveness or safety. Although the tool was designed for HTA, it will be useful for many other users of RWE and will help guide optimized RWE generation.

Abstract Importance The relevance of randomized clinical trials (RCTs) outcomes to real-world settings – especially across countries – is sometimes limited by their restrictive eligibility criteria and variations in standards of care compared to routine clinical practice. Objective To assess the transportability of findings from the RCT Lung-MAP S1400I to real-world populations in the United States (US), Germany and France. Design This empirical validation study used patient-level data from the RCT Lung-MAP S1400I…

Analysis of single arm trials complemented with external comparator arms (ECAs) may be used to support evidence of effectiveness of novel therapies in oncology research when a randomized trial is unavailable or unfeasible. However, the intention-to-treat effect, which is a common target of estimation in ECA studies, is difficult to interpret when there are differences in adherence between the trial and ECA. This paper describes an approach to estimation of per-protocol effects in ECA studies using the target trial…

The trend toward more NICE single technology appraisals of cancer drugs relying on immature survival data are consistent with moves by regulatory agencies to encourage expedited approvals for innovative therapies. For Health Technology Assessment decision-making, it is essential to balance early drug access with the use of robust evidence.