(160) Real-world data collection for medical device regulatory submissions: Considerations in epidemiology

Background: The 2023 draft Food and Drug Administration (FDA) guidance clarifies FDA’s view on real-world data (RWD) and how they are assessed in medical device applications. In addition, the recent adoption in the European Union (EU) of the Medical Devices Regulation [(EU) 2017/745)] and In Vitro Diagnostic Medical Devices Regulation [IVDR, (EU) 2017/746] aligns more closely with the FDA’s risk-based device classification system and adds scrutiny on performance evaluation plans with more rigorous clinical evidence requirements. With many devices up-classified as higher risk under IVDR compared to In Vitro Diagnostic Medical Device Directive (IVDD) and FDA’s recognition of RWD, how can epidemiology support submissions?

Objectives: To describe methods and points to consider when collecting RWD for premarket regulatory decisions.

Methods: In the light of the aforementioned guidance, we reviewed RWD collection methods in clinical performance studies we conducted for 3 FDA and EU regulatory submissions of in vitro diagnostics (IVD) for respiratory diseases.

Results: IVD RWD collection implies clear operational definitions for the study population and variables to minimize misclassification. We conducted the studies in 2021-2022, and used available disease epidemiology information (including incubation period) to develop eligibility criteria and exposure, covariates, and outcome definitions. A comparator, if used, should be chosen bearing in mind its intended use and population. We used 2 FDA-cleared or EUA-authorized tests as reference methods; 1 of 2 tests was selected for discrepancy analysis. Both were intended for the simultaneous qualitative detection and differentiation of multiple respiratory pathogens from individuals with possible exposure. To achieve needed data quality, we created a plan for daily data review and queries, and conducted statistical analyses (e.g., method comparison) using the recommendations in the FDA guidance.

With EU standards now aligning with FDA’s, RWD from one country can be deemed fit-for-purpose by regulatory authorities in other countries. We collected RWD from 5 US states and used them for IVDD and IVDR applications. The sample sizes (n=477 and n=543, respectively) and study design and robustness of variables aligned with EU needs. Statistical analyses were conducted as specified for EU conformance assessments of IVDs according to Medical Device Coordination Group and IVDR.

Conclusions: With the recent international focus on RWD for pre-market regulatory decision-making and with careful methodological planning, evaluation, and collection of RWD, RWE can be powerful in generating insights for a device’s effectiveness and inform benefits and risks for users in US and EU.