Best Practices for ECA Study Design to Support HTA Decision-Making in Europe
Author(s)
Dumoulin O1, Vidalis A2, Proenca C1
1Alira Health, Basel, BS, Switzerland, 2Alira Health, Basel, Switzerland
OBJECTIVES: Despite the increasing integration of real-world data (RWD) into health technology assessments (HTA) for efficacy demonstration, the acceptance of external control arms (ECAs), to support single-arm trials (SAT), differs between countries. This research aims to leverage current experience to develop best practices for ECA design to support HTA decision-making in Europe.
METHODS:
Six technologies that included ECAs in their EMA/FDA submissions between 2017-2021 were identified from the grey literature. The EU4+UK HTA appraisal reports were reviewed and the acceptance of ECAs was evaluated. Six HTA experts from EU+UK were also interviewed.RESULTS:
Of the six technologies the ECA data was accepted on 5/6, 3/6, 2/6, and 1/6 by NICE, AEMPS, G-BA and HAS, respectively. Most technologies received reimbursement, despite the lack of acceptance of ECA data; however, with minimal added benefit due to overall uncertainty of efficacy. We categorized the ECA best practices into study design, RWD source selection, representativeness, impact of bias, statistical analysis, reporting/transparency, and comparability. Manufactures should engage with regulatory and HTA bodies to validate the need for ECA, study design, and RWD sources. Endpoints and analyses should be pre-specified. Patient-level, rather than aggregated RWD, is preferred to allow for adjustment of confounders and robust analyses, such as propensity score methods and Bayesian borrowing. Demonstrating comparability between the SAT and the ECA is crucial. Endpoints should be accurately tracked with RWD sources and match the SAT. Validation of the full evidence generation plan is possible through early HTA advice channels, but not following the advice can be detrimental.CONCLUSIONS:
When robust and appropriate, ECAs have the potential to accelerate patient access to new technologies in diseases with a high level of unmet need. Further collaboration between key stakeholders is needed to define the situations when SAT+ECA are acceptable and the key methodological requirements.Conference/Value in Health Info
2022-11, ISPOR Europe 2022, Vienna, Austria
Value in Health, Volume 25, Issue 12S (December 2022)
Code
HTA218
Topic
Health Technology Assessment, Study Approaches
Topic Subcategory
Decision & Deliberative Processes, Surveys & Expert Panels
Disease
No Additional Disease & Conditions/Specialized Treatment Areas