Aetion’s comments to FDA on data standards for RWD in drug and biological product submissions
Lowell Schiller, JD
Chief Legal and Regulatory Officer, Aetion
Last week, Aetion submitted a letter to FDA commenting on the Agency’s recent draft guidance document Data Standards for Drug and Biological Product Submissions Containing Real-World Data.
The Draft Guidance reflects FDA’s commitment to fostering high quality analyses of real-world data (RWD) that can provide evidence for regulatory decisions across the product life cycle, including regulatory review of safety and effectiveness in the context of product approval decisions. Aetion shares this commitment and appreciates the substantial effort that FDA is putting into developing resources that will further it.
We agree with FDA that when a submission contains RWD, it is important that the data be submitted to the Agency in a usable model and format. Reviewers should be able to characterize, evaluate, and re-analyze the data efficiently, and the data format should facilitate, rather than impede, the Agency’s ability to determine whether the data in a real-world evidence (RWE) study are reliable and relevant, and whether the results are reproducible.
However, we believe that the approach proposed in the Draft Guidance will undermine efforts to generate high-quality RWE more than it will assist. Among the concerns we identified:
- Although converting study data into a supported format may be intended to create efficiencies for both researchers and FDA reviewers, a blanket mapping requirement could diminish study validity and make it challenging for a study to adhere to the recommendations for ensuring transparency across the data life cycle discussed in a draft guidance published in September, Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products.
- Currently, the only relevant standards supported in FDA’s data standards catalog are Clinical Data Interchange Standards Consortium’s (CDISC’s) Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM) formats. These formats were designed for clinical trials and are not optimized for RWE. The resulting mapping process would be cumbersome and potentially impact study validity.
- The labor-intensive nature of mapping data to CDISC SDTM or ADaM while preserving detail is likely to introduce significant delay in the time it takes to execute a study involving RWD. This delay will impede FDA’s access to time-sensitive information that may bear upon the public health, which may have particular impacts in contexts such as a public health emergency like the COVID-19 pandemic or therapeutic areas with rapidly changing standards of care, such as oncology.
We urge the Agency to consider alternate approaches to standardizing the review of RWD submitted to support regulatory decision making. For example, technologies such as centralized, platform-based analytics enable the review and analyses of RWD from a variety of sources, without converting to a single supported data standard. Such an approach could enable reviewers to access to source data in a transparent manner while maintaining information and detail that might be lost in the process of mapping the data to a particular standard.