Acceptability of Using Real-World Data to Estimate Relative Treatment Effects in Health Technology Assessments: Barriers and Future Steps

Highlights•Multiple studies have elicited the views of health technology assessment (HTA) agencies and other key stakeholders on barriers to the acceptance of real-world data (RWD) studies more generally, including concerns relating to methodology (eg, residual biases), data availability, governance and quality, and limited trust in RWD studies, as well as barriers relating to HTA policy and partnerships.•We focus specifically on the barriers to the acceptance of nonrandomized studies (NRS) estimating comparative effectiveness. We outline a pathway determining the acceptance and assign the responsibility for specific barriers to key stakeholders, including (1) evidence-appraisers (HTA agencies), such as providing comprehensive methodological guidelines for conducting NRS, (2) evidence generators (manufacturers), such as whether latest best practices are adhered too, and (3) external stakeholders (eg, data controllers), such as whether there is timely access to high-quality RWD.•We discuss future steps requiring a joint effort between all stakeholders that could facilitate increased acceptability of NRS, including improvements in the quality and accessibility of RWD, use of demonstration projects to benchmark NRS results against RCT evidence and highlight the value and applicability best-practice methods, and ensuring up-to-date and detailed HTA real-world evidence guidelines.AbstractObjectivesEvidence about the comparative effects of new treatments is typically collected in randomized controlled trials (RCTs). In some instances, RCTs are not possible, or their value is limited by an inability to capture treatment effects over the longer term or in all relevant population subgroups. In these cases, nonrandomized studies (NRS) using real-world data (RWD) are increasingly used to complement trial evidence on treatment effects for health technology assessment (HTA). However, there have been concerns over a lack of acceptability of this evidence by HTA agencies. This article aims to identify the barriers to the acceptance of NRS and steps that may facilitate increases in the acceptability of NRS in the future.MethodsOpinions of the authorship team based on their experience in real-world evidence research in academic, HTA, and industry settings, supported by a critical assessment of existing studies.ResultsBarriers were identified that are applicable to key stakeholder groups, including HTA agencies (eg, the lack of comprehensive methodological guidelines for using RWD), evidence generators (eg, avoidable deviations from best practices), and external stakeholders (eg, data controllers providing timely access to high-quality RWD). Future steps that may facilitate future acceptability of NRS include improvements in the quality, integration, and accessibility of RWD, wider use of demonstration projects to highlight the value and applicability of nonrandomized designs, living, and more detailed HTA guidelines, and improvements in HTA infrastructure relating to RWD.ConclusionNRS can represent a crucial source of evidence on treatment effects for use in HTA when RCT evidence is limited.