‘Health Affairs’ Recommendations to Strengthen Expedited Approvals
A Project HOPE Health Affairs blog post offers recommendations that it says FDA should accept in order to address certain ethical issues around the expedited approval of new prescription drugs. An expedited drug enters clinical practice without the same amount or quality of supporting data as one traditionally approved by the agency.
The post recommends increased post-market surveillance and confirmatory trials. It says FDA should be given more resources to reap the benefits of its Sentinel surveillance system. Sentinel is the agency’s post-market active surveillance tool that allows it to query claims and real-world clinical data to help identify associations between specific drug exposures and adverse events. “Nearly a decade after its creation, the methodology for use of these data sets is still in development, and unresolved issues remain related to access for outside researchers,” the post says. “Furthermore, FDA needs to develop Sentinel’s capacity in precision medicine, to help identify how a patient’s genetic and molecular profiles can predict the effectiveness and safety of therapies. Such new knowledge might help resolve the ethical tension between individual- and population-level decision making.”
FDA should also use more effectively its ability to mandate prospective controlled trials as a condition of approval, the post says. Drug makers have had trouble following through with these commitments and doing so in a timely fashion. “In such circumstances, the FDA can impose civil monetary penalties, or remove a drug from the market,” it says. “But the fines are relatively small, and have never been invoked due to administrative complexity. At the other extreme, it is difficult to remove a drug once it is on the market, particularly given pressures from the sponsor, professional organizations, patients, and other stakeholders.”
Additionally, stronger incentives for post-marketing studies should be enacted, Health Affairs says. “One option is for FDA to require Risk Evaluation and Mitigation Strategies (REMS) until required post-marketing trials are carried out,” it says. “REMS are regulatory limitations that require manufacturers to restrict access to providers who have received training and certification or enroll all patients in registries to more closely monitor drug use. Experience with one REMS program has shown that they can substantially reduce prevalence of off-label prescribing. However, the FDA currently only has the power to impose REMS on drugs that have a strong safety signal during pre-approval testing, and drugs tested via expedited development programs may have not yet been given to enough patients to uncover such issues (if they exist). Congress should give the FDA authority to impose REMS on all drugs approved after expedited review to give sponsors strong incentives to carry out additional studies to lift the restrictions.”