The Food and Drug Administration's Accelerated Approval Program was created in 1992 to significantly accelerate the ability to bring certain new drugs to market. New research to be published in an upcoming issues of the INFORMS journal Manufacturing and Service Operations Management reveals a large number of drug manufacturers are failing to complete the approval process, meaning a significant number of drugs on the market are not yet fully approved.
Part of the program's requirement is that manufacturers must complete post-market studies to prove the effectiveness of every drug that has been pre-approved under this initiative. Only then can those drugs be converted to full, regular approval.
But according to this newly published research analyzing publicly available data from 2014 to 2018, those studies are not being completed as promised. From 1992 to 2008, 36% of post-market studies had not been completed, and 50% of the uncompleted studies took an average of five years to even begin.
WHAT'S THE IMPACT
The takeaway for Liang (Leon) Xu, the study's lead researcher and a professor of supply chain and analytics at the University of Nebraska-Lincoln College of Business, is that post-market studies are expensive and not easily enforced, giving manufacturers little incentive to pursue them.
FDA regulators are facing challenges to determine and enforce deadlines because of unbalanced information and moral hazard. They're tasked with optimizing the tradeoff between providing public access to potentially life-saving drugs and mitigating public health risks from ineffective drugs.
Xu, along with fellow authors Hui Zhao and Nicholas Petruzzi, both at the Smeal College of Business at The Pennsylvania State University, take advantage of what's already in place with an eye to increasing the chance of implementing a solution.
Currently, he said, the FDA mandates that manufacturers pay a fixed fee for review of its new drug applications. To ensure the studies get done, he suggests replacing the fixed fee with one tied to a post-market study deadline.
This fee would depend on the probability of a drug's success, and the enforceability of an unproven drug being pulled from the market. The authors also developed an alternative option. In that scenario, if the current fee cannot be altered into a deadline-dependent fee, the analysis can be modified to calculate a single deadline.
THE LARGER TREND
In short, the findings provide insights to regulators on granting pre-approval of a drug under the FDA's Accelerated Approval Program. If the enforceability of a given drug is expected to be low, then regulators should consider requiring a higher success probability before proceeding with conditional approval.