GAO Issues Report on Surrogate Endpoint Accelerated Approvals; Calls for Enhanced OversightNovember 5, 2009
By Kurt R. Karst –
A recent report from the Government Accountability Office (“GAO”), titled “FDA Needs to Enhance Its Oversight of Drugs Approved on the Basis of Surrogate Endpoints,” finds that weaknesses in FDA’s monitoring and enforcement process have hampered the Agency’s ability to effectively oversee postmarketing studies conducted under FDA’s accelerated approval regulations. Senate Finance Committee Ranking Member Charles Grassley (R-IA) requested that the GAO examine FDA’s oversight of drugs approved under FDA’s accelerated approval regulations based on surrogate endpoints.
In December 1992, FDA promulgated final regulations under which the Agency will accelerate the approval of certain new drugs and biologics for serious or life-threatening illnesses, and when such products provide a meaningful therapeutic benefit to patients over existing treatments. These regulations, which are commonly referred to as “accelerated approval,” are located in Subpart H (21 C.F.R. § 314.500) of FDA’s drug regulations, and in Subpart E (21 C.F.R. § 601.40) of the Agency’s biologics regulations. If a product meets these criteria, then FDA may grant marketing approval based: (1) on a demonstrated effect on a “surrogate endpoint” and a sponsor’s commitment to complete with “due diligence” the required postmarketing studies to demonstrate the product’s clinical benefits; or (2) on restrictions to assure safe use (that is, when FDA determines that a drug can be used safely only if distribution or use is modified or restricted). (In clinical trials, a “surrogate endpoint” is an alternative measurement of the symptoms of a disease or condition that are substituted for measurements of observable clinical symptoms.) Importantly, FDA may expedite the withdrawal of approval of an application approved under the accelerated approval regulations if a sponsor “fails to perform the required postmarketing study with due diligence,” or if “[a] postmarketing clinical study fails to verify clinical benefit.” A list of accelerated and restricted approvals is available here.
Interesting, the GAO report notes a shift in the types of products approved under the accelerated approval regulations:
Since FDA began using the accelerated process in 1992, there has been a general shift in approvals based on surrogate endpoints from applications for HIV/AIDS drugs to applications for cancer drugs. In the first 9 years of the accelerated approval process, from 1992 through 2000, applications for drugs to treat HIV/AIDS made up 48 percent of the approvals, while applications for drugs to treat cancer made up 26 percent of these applications. Conversely, from 2001 through 2008, applications for drugs to treat cancer made up over half—59 percent—of the applications approved, while drugs to treat HIV/AIDS accounted for only 18 percent of approved applications. [(See the figure below from the GAO Report)]
Percentage of Approved Applications Granted Accelerated Approval for Cancer and HIV/AIDS Drugs, June 19, 1992–November 20, 2008