Report Criticizes Lack of FDA OversightReport Criticizes Lack of FDA Oversight

A small cloud hovered over the June 30 celebration of the US Food and Drug Administration's (FDA) 100th anniversary in the form of a report, released 4 days earlier, that took the FDA to task for the agency’s lackluster enforcement of laws protecting the nation's food and medical products.

The report, issued by Rep Henry A. Waxman (D, Calif), said that during the past 5 years, the number of warning letters (a notice of violation of federal law) issued by the FDA to companies decreased by more than 50%. Waxman's report also said that officials at FDA headquarters routinely rejected the enforcement recommendations of the agency’s field staff and that the agency's recordkeeping and case tracking practices were inadequate.

“The FDA that has achieved so much in the last century—and that was once the most respected regulatory agency in the world—has seen its powers wither and its reputation plummet over the last 5 years,” said Waxman in a prepared statement. “Today, the agency's historic commitment to public health is in doubt.”

But FDA officials said the agency is doing a good job in an era of restricted budgets, and that tallying raw numbers of warning letters issued fails to capture a shift in enforcement focus to concentrate on fewer but more legally solid cases. In a response to Waxman's report, the FDA said it has won a “string of unprecedented legal actions” against companies in violation of the law and that settlements and penalties since fiscal year 2000 have amounted to more than $2.5 billion.

“FDA enforcement cannot be properly judged by counting the number of actions taken by the agency,” said David Elder, the director of the FDA's Office of Enforcement, in a statement. “FDA has increasingly used an enforcement strategy based on efficient risk management principles that focuses on combating the greatest public health risks and maximizing our deterrent effect against potential violators.”

The report, “Prescription for Harm: The Decline in FDA Enforcement Activity” (http://www.democrats.reform.house.gov/story.asp?ID=1074), found the number of warning letters issued by the FDA decreased from 1154 in 2000 to 535 in 2005 and represented a 15-year low. Over the same time, the number of seizures of mislabeled, defective, and dangerous products declined by 44%. Some could argue the declines reflect better compliance by companies to the laws and regulations. But Waxman's report said observed violations by FDA field inspectors remained relatively stable over the 5-year period (6334 in 2000 and 6268 in 2005), suggesting that compliance has not significantly improved.

Jerry Avorn, MD, chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital in Boston, said he is concerned about the drop in the number of warning letters issued and the message that it sends to manufacturers.

“In the industry, there's a sense that the FDA is minding the store less,” said Avorn, who also commented on the findings in a letter requested and released by Waxman. “This decline in warning letters also came at a time when the problems with Vioxx were going on, and there were problems with product safety on the device side with pacemakers and defibrillators.”

Vioxx (rofecoxib, a cyclooxygenase-2 inhibitor) was pulled voluntarily from the market by Merck & Co Inc, White House Station, NJ, in 2004 after a higher than reported risk of cardiovascular events was uncovered. Last year, Guidant Corp (since bought by Boston Scientific Corp, Natick, Mass) had to recall certain implantable cardioverter defibrillators, cardiac resynchronization therapy defibrillators, and pacemakers after the FDA had determined that there was a reasonable probability that the malfunction of these devices would cause serious adverse health consequences or death.

David W. Feigel, Jr, MD, MPH, a former director of the FDA's Center for Devices and Radiological Health, said Waxman's report and the arguments raised by FDA leadership are both partially right.

“Is Waxman correct? Yes. Is there a single cause for the problem? Probably not,” said Feigel who is now a research professor at Arizona State University in Tempe. “The situation is a culmination of a variety of trends—and some of which Congress has some culpability in.”

Feigel said Congress continues to underfund the FDA's enforcement efforts to the extent that inspections of certain medical products that are supposed to occur every 2 years take place every 5 to 7 years. Senators Chuck Grassley (R, Iowa), Mike Enzi (R, Wyo), and Ted Kennedy (D, Mass) have all proposed legislation to beef up FDA enforcement, but political wrangling over the issue makes passage of these bills questionable. Although the new report was the culmination of a 15-month investigation initiated by Waxman and Rep Tom Davis (R, Va), chairman of the House Committee on Government Reform, when it was released it was labeled a minority report with only Waxman's name attached to it.

Waxman's office said Davis was asked to be a part of the report but declined. Telephone calls from JAMA to Davis' office seeking clarification on the issue were not returned. After the release of Elder's statement, the FDA said it would not comment further on Waxman's report or its allegations.

In addition to Congress's underfunding of the FDA, the Bush administration's appointment in 2001 of Daniel Troy as FDA's chief counsel—the first time the position was a political appointment and not a hire from within the agency—was widely perceived as a signal of the politicization of the agency's mission. Troy began cutting back on perceived FDA enforcement parameters, arguing the agency had assumed oversight not stated in law that led to courts frequently overruling FDA actions.

This philosophical shift was demoralizing on FDA field staff, Feigel said. “There's a perception that FDA has become an apologist for industry instead of being tough on them,” he said. “The staff perceived they had their authority taken away and given to the politicians. Companies could meet directly with Troy and decisions would be made without input from FDA staff.”

But whether the FDA's current model of business is driven by budget constraints or political philosophy, many in the medical community are concerned about what they believe is a growing laxity in both surveillance and enforcement by the agency, said Avorn.

“Dan Troy came in saying the FDA was doing too much enforcement and that on his watch there would be less of that—and he followed through on his words,” Avorn said. “This [minority report] is not just a fantasy of Waxman’s.”

The US Food and Drug Administration's (FDA’s) handling of postmarketing studies promised by pharmaceutical manufacturers has come under fire in a new report by the Department of Health and Human Services' Office of Inspector General (OIG).

Postmarketing studies following FDA approval of new drugs are intended to give regulators and researchers additional information regarding the safety and efficacy of the new medicines because the number of patients enrolled and adverse effects detected during the randomized trials that lead to drug approval are limited relative to the population exposed once the drug is approved. While the FDA has the authority to require postmarketing studies only in certain situations, such as following accelerated approval of a new drug, these studies usually are requested by the agency and are agreed to by the pharmaceutical companies.

But prompt release of data by the drug companies does not always happen. Federal law requires drug applicants who agree to perform postmarketing studies to submit annual reports on the status of the research. However, the OIG report said that 35% of the annual status reports that should have been submitted in fiscal year 2004 had not been made or contained no information on their progress. This report follows a study released last year by Rep Edward J. Markey (D, Mass) showing that only 49 of 91 postmarketing studies required by the FDA of drug manufacturers participating in the accelerated approval process had been completed—half of the other 42 studies had not even been started.

The OIG report, released July 7, also contends that even completed annual reports lacked useful information for monitoring the progress of postmarketing study commitments and that the FDA does not have effective management information systems for monitoring the documents. In its comments included in the OIG report, the FDA disagreed with the findings that it cannot readily identify whether postmarketing study commitments are progressing toward completion and are doing so in a timely manner.

In any event, the OIG recommended that the FDA instruct drug applicants to provide additional, meaningful information in their annual reports, improve the management information system, and ensure that drug manufacturers' commitments for postmarking studies are being monitored and validated.

The report, FDA's Monitoring of Postmarketing Study Commitments, is available online at http://www.oig.hhs.gov/oei/reports/oei-01-04-00390.pdf.—M.M.