Another great conference session this afternoon: “Timing Is Everything: Balancing Access and Uncertainty.” This one was moderated by Jeff Skopek, with presentations by Shannon Gibson, Trudo Lemmens, and Efthimios Parasidis.
First, we heard from Gibson and Lemmens on “Overcoming ‘Premarket Syndrome,’” AKA the various problems associated with relying solely on premarket data for safety and efficacy determinations. These problems include the fact that industry studies have been shown to be more likely to be biased in favor of demonstrating a positive result, and premarket studies also cannot really demonstrate how a product will be used in clinical practice. Moreover, for niche market drugs (e.g., those for orphan indications or pharmacogenomics), which are becoming more and more popular, there are fewer patients available to serve as clinical trial subjects, thereby inherently limiting the data that may be generated prior to approval and increasing uncertainty around safety and effectiveness.
So what should we do? Develop an improved post-market research agenda, say Gibson and Lemmens, and explore “adaptive licensing,” by which they mean rendering regulatory decisions based on the entire body of evidence collected throughout a product’s life cycle. They argue that drug access decisions should not be binary, but instead, should be incremental and continually reassessed based on new data, including data that becomes available after a drug has been initially made available to patients. They closed by pointing out the importance of data transparency at all points in drug regulation.
Next, we heard from Efthimios Parasidis on “Innovative Regulating as a Public Health Imperative.” Parasidis focused on the ways in which FDA can leverage its existing post-market regulatory authorities granted under the Food and Drug Administration Amendments Act of 2007, including requiring post-market studies and imposing Risk Evaluation and Mitigation Strategy requirements (REMS).
Arguing that FDA really must take a proactive approach to post-market safety, Parasidis suggested four steps for the agency:
- Require active post-market surveillance for all FDA-approved products
- Create a practical administrative structure for the monitoring process
- Set guidelines for analysis and disclosure of relevant health information, including distinguishing true signals from noise
- Permit and encourage independent analysis of safety and efficacy, through collaboration with public and private entities such as state and federal health agencies, health insurers, and the like
He described the various limitations and problems associated with relying on state law tort actions to address drug safety in the post-marketing stage, including federal preemption and the vagaries of litigation. However, he maintained that state tort claims should be retained as an important mechanism by which to incentivize compliance, particularly in the event that a company failed to comply with any post-marketing requirements imposed by FDA.
Parasidis concluded with a Congressional “wish list” in which he called for amendments to the Food, Drug, and Cosmetic Act to eliminate limitations on when FDA can require post-market studies and REMS and to incorporate active post-market surveillance as a requirement for all marketed products, statutory action to link federal preemption laws to satisfactory completion of post-market obligations, and ultimately, greater funding to FDA to accomplish its regulatory mission.
During the Q&A period, Parasidis clarified that his arguments related to post-market surveillance apply with equal force to generics. We also heard a concern from the audience that adaptive licensing and allowing drugs on the market more quickly can actually impact the ability to collect data on those drugs as patients become less willing to enroll in research as a way of obtaining access. Ultimately, this effect may mean that it takes longer to gather the essential evidence about a given product. Finally, we heard a few suggestions for how FDA’s post-marketing obligations could be funded, including a small surcharge on all prescriptions.