Drug sponsors are eager for the FDA to embrace real-world evidence (RWE), but several companies are asking the agency to clarify how it can be used in clinical trials.
Late last year, the FDA invited public comments on a plan for its real-world evidence framework, and it received 30 overall, nine from drugmakers.
One of the major threads in the comments was about data: specifically connectivity, gaps and capture. The framework “does not provide clarity regarding the kinds of data standards required, who is responsible for developing data standards or the process by which FDA will assesses the acceptability of those standards,” Janssen wrote. “Will FDA require different data standards for different data sources (e.g., health insurance claims vs. electronic health records) or for different types of regulatory decisions?”
Another thread was about evidentiary standards and adequate scientific evidence. “There is not enough detail for sponsors to know whether their evidence will satisfy these criteria. We realize that the practice of using RWE for regulatory decision-making outside of addressing safety questions is still in its infancy,” Janssen added.
Some sponsors also latched on to language that suggested the agency might be open to using observational studies that “replicate” randomized trial results and were worried that the word is a little too vague. Sanofi, for instance, urged the FDA to declare that observational studies can be used “to elucidate the degree of consistency” between randomized control trials and observational studies.
Janssen, too, said it had many questions about replicating randomized trials — how will the agency determine how feasible replication is, and which trials would be subject to replication? How will regulators deal with “confounding” studies? Does the agency have metrics for how well randomized trials and real-world evidence line up?
Novartis also suggested that sponsors should be more prominent in the demonstration projects that the FDA is developing. The company commented on the “clear lack of industry (i.e., drug sponsors) participation” in those projects.
Regeneron suggested that the FDA “provide some discussion points to assist sponsors in how best to apply practices or lessons learned from these programs to planned or future studies to assist in regulatory decision-making, particularly in areas of high unmet medical need.”
Novo Nordisk said it would like to see examples of adaptive or Bayesian trial designs, which the FDA has said might help qualify biomarkers for trials. The agency should also be open to using preclinical data for biomarkers, Novo said.
