Congress’ Remedy for Post-marketing
When the Food and Drug Administration (FDA) approved Merck’s quadrivalent human papillomavirus vaccine (Gardasil) on June 8, 2006, the agency extracted some post-approval commitments from the company, as it frequently does when it “green-lights” an important new drug around which questions still revolve. Those commitments involved additional testing of Gardasil after it went on the market, particularly in girls 11 to 12 years of age. Only a small number of girls in this age group had participated in Merck’s clinical trials, and these trials were submitted as evidence of the drug’s efficacy and safety. That patient population would loom large in the months after the FDA’s approval as Merck mounted a political campaign to convince states to require the vaccination for sixth-grade girls.
However, the post-approval studies that Merck agreed to perform would not start before June 2009, if then. That short-term safety surveillance study is set up to follow 44,000 vaccinated subjects for just 60 days to monitor visits to hospital emergency departments and for six months to monitor chronic problems such as autoimmune disorders, rheumatologic conditions, and thyroiditis. Merck must include a “sufficient” number of children (ages 11 to 12), although no number is specified in the FDA’s charge to the company. canadian pharmacy support net
Other companies that have committed to similar post-approval studies have dragged their feet and, in some instances, have simply ignored the FDA. The FDA has no authority to force a company to complete a study. Even when a study is finished and the FDA receives the data, there is no guarantee that the results—if they are in any way disquieting—will prompt a suitable reaction on the part of the agency, such as immediately requiring new labeling or, in more serious instances, pulling the drug from the market.
In the past few years, a number of unfortunate instances, particularly the rofecoxib (Vioxx, Merck) fiasco, have shown that it is easy for the FDA, because of shortcomings in the data, as well as because of bureaucratic malaise and communication gaps, to miss credible warning signs of drugs “gone wild,” producing numerous adverse reactions.
During the past couple of years, these and other potential problems have been highlighted, first by the U.S. Government Accountability Office (GAO) and later by the Institute of Medicine (IOM), whose report was requested by the FDA. Both the IOM and the GAO cite the failure of drug companies to complete post-marketing studies on time; they also cite the FDA’s lack of authority to compel timely completion.
Serious limitations also afflict the FDA’s MedWatch system, which catalogues reports of adverse drug events (ADEs). Moreover, even when troublesome signs appear after a drug is on the market, that evidence might not be available to the FDA’s Office of Surveillance and Epidemiology (OSE), formerly known as the Office of Drug Safety (ODS). The OSE is set up to ensure that post-marketing problems receive quick attention. It is subservient to the FDA’s Office of New Drugs (OND), which has considerably more stature within the Center for Drug Evaluation and Research (CDER) and which has sometimes been criticized for turning a blind eye to emerging evidence of late-blooming safety questions about new drugs. buy prescription drugs online
Sheila Burke, MPA, RN, Chair of the IOM committee whose members wrote its report, says:
We found an imbalance in the regulatory attention and resources available before and after approval. Staff and resources devoted to pre approval functions are substantially greater. Regulatory authority that is well defined and robust before approval diminishes after a drug is introduced to the market. Few high-quality studies are conducted after approval, and the data are generally quite limited.
These weaknesses explain why post-marketing surveillance of drugs is the marquee issue as a major FDA reform bill sashays (or, more appropriately, staggers) down the red carpet of the Congress to the White House—because senators tussled over multiple amendments when that bill, the Prescription Drug User Fee Act (PDUFA) Reauthorization (S. 1082), came to the Senate floor this past May. Controversial amendments involving drug importation and the approval of follow-on copies of biotechnology drugs were removed from the PDUFA bill. However, although there were pitched battles over the provisions in another amendment, the FDA Revitalization Act, sponsored by Senator Edward Kennedy (D-Mass.), there was no question that the post-marketing reforms in the Kennedy bill would be included in the final PDUFA bill, and they were. However, those post-marketing changes were not nearly as far-reaching as Senator Charles Grassley (R-Iowa) had wanted; he had also sponsored a competing FDA post-marketing reform bill.
The House of Representatives is likely to adopt the provisions of the Senate’s bill on post-marketing surveillance, and the bill will probably be sent on to President Bush to sign; he says that his signature will be forthcoming. But before we look at these changes in the Senate bill, it is necessary to outline the problems they aim to resolve.
The FDA’s MedWatch system is the agency’s first line of defense against a newly approved drug whose side effects, whether or not they have been acknowledged in clinical trials, cast a much darker shadow than previously thought. Physicians, pharmacists, patients, and drug companies send in reports of adverse reactions as the drug begins to be used and potential problems become evident. But even the FDA has admitted the system’s shortcomings. In a November 2006 speech, Scott Gottlieb, MD, Deputy Commissioner for Medical and Scientific affairs at the FDA, acknowledged that MedWatch is a valuable tool but “we know that it is not being used as effectively as it ought to be.”
The FDA and other agencies go by this general rule: for every 10 adverse reactions reported, only one report is submitted to the FDA. Of course, even that minimal number of reports can be useful. silagra 100
An example is Sanofi-Pasteur’s Menactra, a vaccine designed to prevent bacterial meningitis. The FDA approved that vaccine on the basis of clinical trials involving 7,000 children, none of whom had contracted Guillain-Barre syndrome (GBS), a neurological disorder. But lo and behold, when the drug reached the market, reports of GBS developing in the children after inoculation with Menactra began to filter in to the Vaccine Adverse Events Reporting System (VAERS). VAERS is the Center for Biologics Evaluation and Research’s version of
MedWatch. Initially, there were only five reports. The FDA decided not to change Menactra’s labeling, because those five reactions were expected to be the norm with the introduction of a new vaccine. At the time, however, the FDA noted that ADEs associated with the vaccine were not always being reported and that there might be additional cases that the agency might not be aware of.