In September 2021, the United States Food and Drug Administration (FDA) issued a draft guidance, “Real-Word Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products.” The comment period initially closed on November 29, 2021. However, the FDA received requests to extend the comment period “to allow sufficient time to develop and submit meaningful comments,” to which the FDA responded by extending the comment period until January 24, 2022. Taking advantage of the extended comment period, many industry participants submitted comments, requesting more flexibility and clarity from the agency on how to use real-word data (RWD) from electronic health records (EHRs) and medical claims to support regulatory decision-making.
The guidance focused on three issues related to the use of RWD pulled from EHRs and claims data: (1) the selection of data sources that appropriately address the study question, (2) development and validation of definitions for study design elements, and (3) data provenance and quality throughout the study lifecycle. While many of the comments were positive feedback for the agency, appreciative of the transparent and detailed approach, they also asked for more clarity around metrics of quality data, study validation variables, and the timeline and framework for interactions between the agency and industry.
Comments
The Pharmaceutical and Research Manufacturers of America (PhRMA) submitted a comment, asking the FDA to work with interested stakeholders to develop a framework regarding quantitative and qualitative metrics of data quality, with the goal of that framework becoming an appendix to the final guidance. PhRMA also asked for flexibility around validation, suggesting that the variables of importance could be specified for validation, which would allow sponsors to submit those plans to the FDA in the protocol for discussion before the study begins.
Biotechnology company Amgen also noted that the guidance could better outline ways to seek agreement with the FDA on variables that require validation, writing, “We agree that validation is an important aspect in any study design, but there will be circumstances when validation may not be always needed or useful (e.g., when validation studies have been previously conducted in the same data source).”
RWD provider Flatiron Health also submitted comments, favoring a risk-based approach to study-specific verification and validation, writing, “It is currently challenging for a retrospective observational study using RWD to generate the same level of evidence as a clinical trial or a prospective observational study with intentional data capture. The Final Guidance would benefit from clarification of this point.”
The RWE Alliance, a coalition of RWD and analytics organizations, asked the FDA to “acknowledge explicitly” in the final guidance that it will consider specific circumstances of an RWE study when evaluating the suitability of using data from a particular source for a specific regulatory purpose.
The Biotechnology Innovation Organization (BIO) also called on the FDA to offer regulatory flexibility, noting that the draft guidance focused on studies aimed at determining causal inference, but RWD could be used to fill critical evidence gaps in benefit-risk and safety assessments. “For example, this would include an approach tailored for aggregated data and data used to establish natural history, standard of care, or to add context to the results of an RCT,” BIO wrote.