Congress’ Remedy for Post-marketing part 3
The agency’s own statistics for 2006 show that drug companies failed to initiate more than 70% of post-marketing studies that they committed to performing during that year; 899 of the 1,259 post-marketing studies (71%) promised had not begun as of September 30, 2006. This was an increase of 5% over fiscal year 2005. When that report first came out, Representative Rosa DeLauro (D-Conn.), Chairman of the House Appropriations subcommittee, which approves the FDA’s annual budget, said:
This report clearly demonstrates that drug companies do not intend to keep these promises and that drug companies are taking advantage of FDA’s lack of authority to require these studies. canadian antibiotics
However, PhRMA’s Dr. Loew has a different take on the numbers:
While it is true that 71% of open commitments are considered ‘pending,’ these ‘pending’ studies are in the preparatory phase of clinical trial development during which the protocol is drafted and submitted to FDA, IRB approval is obtained and the sponsor begins recruiting clinical investigators. If sponsors simply failed to initiate such studies, the studies would be coded as ‘delayed’ rather than ‘pending.’ However, only 3% of open studies are considered to be ‘delayed.’
No one disputes the value of post-marketing studies. Nothing bears out their worth better than the pediatric studies performed by drug companies in order to get an extra six months of marketing exclusivity, which the Best Pharmaceuticals for Children Act (BPCA) grants them.
For example, a 2007 GAO report about this act showed that about 87% of the drugs that were granted pediatric exclusivity under BPCA required labeling changes—often because the pe-diatric drug studies found that children might have been exposed to ineffective drugs, ineffective dosing, overdosing, or previously unknown side effects.
And no one disputes the fact that the FDA does not have the authority to compel drug companies to complete studies. The Kennedy bill changes that by allowing the FDA to force companies to accept REMSs when it approves a new drug. A REMS could require that a company conduct post-approval studies, such as a prospective or retrospective observational study, or even a clinical trial, if a study was thought to be an insufficient means of assessing a signal of a serious risk or of identifying an unexpected serious risk. In addition, for the first time, the FDA would be able to issue civil fines of up to $250,000 for not meeting a study deadline, with the amount of the penalty doubling every 30 days, up to a total of $2 million—figures that Senator Grassley insisted be increased from the $10,000 and the $1 million levels in the Kennedy bill. The Senate agreed by a strong majority. online pharmacy without a prescription
However, by a narrow vote of 46-47, Senator Grassley failed to establish a separate safety office within the CDER that would have equal standing to the OND. Both the IOM and the GAO highlighted the institutional weakness of the OSE, which at the time of the GAO report was called the Office of Drug Safety (ODS).
The GAO report from March 2006 described the OSE as subservient to the OND. When the GAO finished its report, the office had had eight different directors in the previous 10 years. The GAO said that the ODS’s Division of Drug Risk Evaluation was responsible for culling data on adverse drug reactions from MedWatch and for making recommendations to the OND. However, the “new drug folks” did not always listen closely to that advice, and they even barred ODS staff members from appearing before FDA advisory committees when those committees were meeting to recommend the approval of new drugs and handle other matters.
Equally disconcerting was another GAO finding: even when the ODS made recommendations to the OND, no one at the ODS stayed abreast of that particular problem to see how events played out.
Steven Galson, MD, MPH, Director of the CDER, has attempted to at least partially correct those bureaucratic disconnects by elevating the OSE to report directly to him, instead of through the OND. In addition, he established a new position of Associate Center Director for Safety Policy and Communication to focus on developing and implementing broad drug safety and communication policies. Senator Grassley wanted to go further by setting up a separate drug safety office on a par with the OND, but the Senate rejected that approach. The Kennedy bill does not address the OND/OSE imbalance at all.
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However, a second Kennedy bill, called the Enhancing Drug Safety and Innovation Act, which was also included in the PDUFA reauthorization, attempts to broaden the flow of clinical trial data into the FDA’s hands. It sets up a new national FDA-administered clinical trials registry and requires that all clinical trials supporting applications for drug approval, as well as all clinical trials conducted with federal funding, be included in that registry. When Senator Kennedy introduced this act on the Senate floor, he explained the need for this new FDA registry by referring to results from clinical trials on selective serotonin reuptake inhibitor (SSRI) antidepressants, which have been linked to suicide in teenagers.
He noted, “Tragically, such information was not adequately available.”
However, all sorts of caveats are in the bill, allowing the Secretary of Health and Human Services (DHHS) to waive reporting requirements. (The FDA is part of the U.S. DHHS.)
Moreover, although it is difficult to argue with the [rationale] for requiring quicker publication of clinical trial data, it is important to keep in mind the limitations of that data. When she appeared before the House Energy and Commerce Committee on May 9, Marcia Crosse, Director of Health Care Issues for the GAO, explained:
Clinical trials typically have too few enrolled patients to detect serious adverse events associated with a drug that occur relatively infrequently in the population being studied. They are usually carried out on homogen[e]ous populations of patients that will actually take the drugs. For example, they do not often include those who have other medical problems or take other medications. In addition, clinical trials are often too short in duration to identify adverse events that may occur only after long use of the drug. This is particularly important for drugs used to treat chronic conditions where patients are taking the medications for the long term. Kamagra Oral Jelly
Given the major problems that the FDA has had in recognizing the initial warning signs of questionable safety and efficacy associated with some new drugs, maybe it is too much to ask that Congress fix those problems in one fell swoop. Certainly, giving the FDA the authority to fine companies who miss deadlines for post-marketing studies gives the agency important new leverage. And the clinical trials registry can’t hurt. But to the extent that the OSE remains a weak cousin within the agency and to the extent that the MedWatch system remains as leaky as a New Orleans levee in the wake of Hurricane Katrina, it is likely that a new Vioxx-type situation will occur, perhaps sooner rather than later.