Zachary Brennan
Senior Editor, Endpoint News
Back in late September, the FDA released a long-awaited guidance on how the industry might use electronic health records (EHRs) or medical claims data in clinical studies to support a regulatory decision for effectiveness or safety.
FDA+ guidance roundup: Benefit-risk assessments, RWE to support regulatory decision-making, and more
The draft guidance offered some light from FDA on which strategies might help a sponsor get a new approval across the finish line or help with an sNDA or sBLA. A total of 57 comments were filed on the draft, with some companies like Regeneron, Janssen, and Amgen, as well as industry groups like PhRMA and the RWE Alliance, seeking additional clarity and offering suggestions.
Amgen, for instance, called on the FDA to provide more specific guidance “to enable data providers to generate consistent assessment reports for data quality that will meet the Agency’s needs as part of a sponsor’s regulatory submissions.”
While noting some circumstances when validation may not be always needed or useful (“e.g., when validation studies have been previously conducted in the same data source”), Amgen suggests variables of importance for validation “could be discussed and agreed to with FDA before the study begins as part of an early interaction with the FDA. This process could be outlined in the guidance.”
Regeneron called on FDA to recognize that this is a “dynamic topic” and to provide additional details on the submission of the protocol or statistical analysis plan, the types of interactions that sponsors should expect (e.g. meeting/written feedback), timelines for such feedback, etc.
“Regeneron encourages the Agency to outline its process within this or another referenced guidance document to assist sponsors in understanding the Agency’s expectations on engagement in this area, with the overarching objective of contributing to decision-making,” the company said.
Flatiron, which is owned by Roche but operates independently, requested a meeting with the agency and said it believes there are certain topics that are broadly applicable to the generation of RWE that would benefit from FDA input (e.g. concerning platforms, processes and technical issues relating to converting RWD to FDA-supported data standards).
The RWE Alliance, which includes Flatiron and Aetion among its partners, also mentioned that FDA should provide additional methods of communicating new information.
Such methods might include a dedicated section of the review memoranda published by FDA regarding an approval decision with real-world data, a centralized “dashboard” on the data on FDA’s website, and/or a periodic report of actual use cases that “aggregates the Agency’s observations about RWE studies that have not met regulatory expectations, to the extent permissible under FDA’s information disclosure laws.”
Aetion noted that a software platform could address many of the draft guidance’s recommendations, although “there are some aspects that are beyond the scope of a sponsor and an analytics platform to address without information from the data source.”
The company also called for FDA to provide recommendations in the final guidance on how sponsors and analytics providers “should evaluate the level of available information when deciding whether to use a commercially available dataset in a study.”
And Duke-Margolis called for several specifics too, such as ensuring that sponsor and data curators collaborate to develop SOPs that offer transparency around data curation approaches.
“Both sets of stakeholders should have opportunities to engage with academic researchers and the FDA to vet these data curation approaches,” the center said. It also sought “FDA identification of analytical tools and strategies deemed acceptable to the agency to address bias and confounding due to missing data or misclassification of data. [And] FDA support for convenings to build consensus on what constitutes acceptable quality for combining data from multiple sources and strategies that can address issues and complexities associated with the use of data linkage to address missing data.”
Source: https://endpts.com/amgen-regeneron-and-others-seek-more-detail-from-fda-on-real-world-data-plans/