The Food and Drug Administration (FDA) has been lax in permitting numerous drugs designed to treat life-altering illnesses—such as HIV/AIDS or cancer—to remain on the market without their manufacturers providing required follow-up studies to show their effectiveness, according to a new Government Accountability Office (GAO) study.
Between 1992 and 2008, the Food and Drug Administration (FDA) approved 90 applications for drugs using an accelerated approval process to quickly get to market drugs aimed at treating serious or life-altering illnesses. However, weaknesses in FDA's monitoring and enforcement process have hampered its ability to effectively oversee post-marketing studies of many of those drugs, GAO said.
In efforts to expedite approval of these drugs, FDA began in 1992 to use a process based on "surrogate endpoints," which required that "drug sponsors complete post-marketing studies to confirm the drug's clinical benefit." These endpoints can include laboratory measures, such as blood pressure—instead of more direct clinical evidence, such as preventing strokes.
"Once those drugs are on the market, the FDA needs to monitor the outcomes," said Sen. Charles Grassley (R-IA), the ranking minority member of the Senate Finance Committee, who had requested the study. "The report should serve as an impetus for the FDA to improve the post market surveillance of these drugs, giving patients and their doctors' meaningful information and necessary safeguards."
FDA had required drug sponsors to conduct 144 post-marketing studies associated with the 90 applications. By the end of 2008, two-thirds of the applications were classified as closed—meaning that drug sponsors had met FDA's requirements for these studies. However, a third of the remaining studies have been classified by FDA as "open" for an extended period.
Although FDA has authority to expedite removal of a drug from the market if a sponsor does not complete a required study—or if a study fails to confirm a drug's clinical benefit, it has not specified the conditions that would prompt it to do so, GAO said.
One of the examples is the case of Shire Laboratories'ProAmatine, a medication used for low blood pressure. The required study been incomplete since 1996. In its study, GAO found that ProAmatine had generated more than $257 million in sales up through 2008, even though "the clinical benefit of the drug has never been established."
FDA officials this summer indicated that they planned to issue a final administrative action letter to the sponsor of ProAmatine and generic manufacturers in a final effort to obtain completion of the required study, GAO said.