WASHINGTON, D.C.—Long-standing concerns over the U.S. Foodand Drug Administration's (FDA) oversight of post-market drug safety continueto plague the regulatory agency, three years after the investigative arm ofCongress made key recommendations to address these weaknesses, according to arecent Government Accountability Office (GAO) report.
The report, issued in November, follows up on a 2006 GAOreview of the FDA's process for monitoring the safety of marketed drugs. Thereport was requested by Rep. Henry Waxman, D-Calif., and Sen. Ted Kennedy,D-Mass., after the FDA approved the blockbuster pain drug Vioxx, only to pullit from the market in 2004 after it was linked to a high incidence of heartattack and stroke.
In its 2006 report, the GAO found that the FDA had notclearly defined the roles of two offices involved in making decisions aboutpost-market safety—the Office of New Drugs
(OND) and the Office of Surveillance and Epidemiology (OSE).The GAO also expressed concerns about limitations in the data FDA relies on toidentify post-market drug safety issues and the systems it uses to track suchissues.
The GAO made a number of recommendations to address theproblems it identified, including that FDA improve the independence of itsprogram for resolving scientific disputes related to post-market drug safety.In 2007, legislation further expanded FDA's
But in following up on its earlier report, per the requestof Sen. Charles Grassley, R-Iowa, the GAO found that the "FDA is beginning toaddress previously identified weaknesses in its oversight of post-market drugsafety issues, but challenges remain."
Specifically, the FDA is changing its post-marketdecision-making process as part of its Safety First Initiative, which includesformalizing interactions between OND and OSE and providing OSE with addedresponsibilities. But the one authority FDA transferred from OND to OSE is apre-market review responsibility, the GAO notes.
"FDA officials said the agency plans to transfer authorityfor two postmarket responsibilities for reviewing certain types of drug safetystudies, but the agency does not have a timeframe for their transfer," the GAOsays. "Officials said that OSE must still gain experience leading the onetransferred responsibility and expand its staff before it can assume theseadditional responsibilities. While most of the OSE and OND employees GAOinterviewed indicated that OSE's role in managing safety issues has increasedsince 2006, most OSE employees GAO interviewed said that OND's perspectivestill carries more weight in decision-making."
According to the report, OND recently created safetymanagement positions in each of its 17 divisions; OSE expanded its similarpositions from 9 to 25, although an employee said turnover has made itdifficult for the OSE managers to gain experience.
"FDA is also revising its program for resolving scientificdisputes, but these changes have not increased its independence, as GAOrecommended," the report points out.
The FDA plans to implement new data systems and isincreasing access to external data to assist with drug safety decisions, thereport continues. The agency plans to implement new systems in 2010 to improvethe timeliness, quality, and analysis of reports of adverse events associatedwith human drug use. The FDA has also increased funding for contracts withprivate companies and is in the early stages of forming partnerships withfederal data holders to access external data.
"As mandated in the 2007 legislation, FDA is developing theSentinel System, a network of external data providers intended to enhance drugsafety surveillance, but the agency is in the early stages of developing it,"the GAO notes.
Finally, the report found that the FDA is still barelytreading water when it comes to meeting an expanded workload. In fact, FDAofficials told the GAO that expanded responsibilities resulting from the 2007legislation increased its workload, and both OND and OSE employees describeddifficulties meeting their responsibilities. The FDA indicated that sincefiscal year 2008, OND staff increased from 736 to 928 and OSE staff increasedfrom 114 to 193. However, an agency review suggests that OSE may still need tomore than double its staff of 193 by fiscal year 2011 to meet its newresponsibilities, the report states.
"Although OSE has increased its staff, officials cited hiringchallenges, such as competition from the private sector, that may make itdifficult to hire staff quickly enough to meet the increasing workload," theGAO states. "FDA also expects to complete a growing number of drug safetystudies, but technological and staffing challenges limit its capacity toconduct these studies. To assist its decision-making, FDA has increasinglysought advice from members of its external drug safety advisory committee.However, the agency has encountered difficulty filling several committeevacancies. An official said FDA is reviewing candidates with the goal offilling these vacancies as soon as possible."
In short, while the FDA has acted on some of the GAO's 2006recommendations, "this has not moved along very quickly," admits Marcia Crosse,director of healthcare at the GAO."We want to maintain some focus on this, to essentially say'yes, you have made progress, but we believe this component is still lacking,"Crosse says.
That component, at the forefront of the GAO's newrecommendations, involves the FDA's development of a comprehensive plan toprepare OSE for the transfer of additional regulatory authorities from OND.According to the report, the FDA agreed with the GAO's recommendation.
The FDAsaid it intends to give the OSE more responsibilities, but only after itsnearly 200 employees gain the experience and resources needed to take on thosetasks.
But while the GAO agrees that both funding and staff areimportant to the successful transfer of these regulatory authorities, the GAOnotes that the FDA has the flexibility to align its resources in such a way asto ensure that post-market drug safety receives appropriate attention.
"The FDA has the resources to do it—it just got a hugesupplemental and regular, annual appropriations increase this fiscal year,"Crosse says. "However, these types of changes take time. Our main concern isthe timeframe in which these changes occur."
For Grassley, those changes can't come soon enough, as hisoffice issued a statement Dec. 9 saying simply, "No more time should be wastedat the FDA in establishing independence for its post-market surveillance."