FDA Blamed for Poor Monitoring of Off-Label Drug Promotion

The Food and Drug Administration (FDA) lacks adequate infrastructure to carry out its responsibility of regulating prescription drug marketing activities, especially promotion for unapproved (“off-label”) uses, the Government Accountability Office (GAO) has found.

In a report released in July, the GAO stated that the FDA is able to review only a small fraction of the marketing materials and activities it is supposed to regulate and has no specific mechanisms to detect off-label promotion. The GAO criticized the agency for lacking a system to keep track of all the materials submitted, reviewed, and acted on.

Although the FDA does not regulate medical practice or physicians' prescribing decisions, pharmaceutical companies are prohibited from promoting their drugs to health professionals or the public for indications not approved by the FDA. The promotional materials and activities must also comply with other requirements such as omitting or minimizing risk, overstating effectiveness, and making unsubstantiated claims of being superior to competitors.

The FDA's Division of Drug Marketing, Advertising, and Communications (DDMAC) is responsible for overseeing pharmaceutical promotion and ensuring compliance with the above rules. Promotional materials and activities such as advertisements for health professionals and consumers, television and radio advertisements, Web sites, sales representatives' interaction with health professionals, marketing activities at professional conferences, and company-sponsored public health campaigns are all within the division's jurisdiction.

At the request of Sen. Charles Grassley (R-Iowa), a ranking member of the Senate Committee on Finance, the GAO conducted the review specifically on the agency's regulation of off-label promotion of drugs.

Between 2003 and 2007, the FDA received approximately 277,000 submissions of final promotional materials submitted from drug companies as required by law. The agency could not provide any data on the percentage of materials reviewed, the prevalence of violations identified in reviewed materials, the average length of a review, or the status of reviews because the agency does not keep track of every submission received, review conducted, violation identified, regulatory action taken, and outcome reached.

According to the report, the FDA is unable to review all promotional materials submitted by pharmaceutical companies because of the large volume. Although the agency claims to prioritize its reviews, it “does not prioritize its reviews in a systematic manner but rather relies on its staff to sort through large volumes of material” and select a fraction of them for review.

“As of March 2008, DDMAC had the equivalent of 44 full-time staff devoted to overseeing prescription drug promotions,” the report stated.

Monitoring for off-label promotion is not limited to review of submitted materials. Violations may take place at conferences, in physicians' offices, and at continuing medical education sessions. The FDA has to rely mostly on physicians' complaints to identify these violations. From 2003 through 2007, “According to DDMAC officials, the FDA received and investigated an average of 150 complaints annually on possible promotional violations,” the report noted. “However, they could not provide ... the total number of their monitoring and surveillance efforts because this information is not tracked.”

A tracking system had been recommended in a previous GAO audit of DDMAC in 2006, but the recommendation has not been adopted. The U.S. Department of Health and Human Services commented in this report that such a tracking system would not improve the FDA's ability to identify promotional violations. The GAO disagreed.

Once a violation is detected, the FDA sends an untitled letter or a warning letter, depending on the severity of the violation, to the manufacturer to demand corrective action. From 2003 through 2007, the FDA issued a total of 117 regulatory letters to drug companies on all types of violations, including 42 letters citing off-label promotion, according to the report.

The duration between the FDA staff's first drafting a regulatory letter and issuing it averaged seven months, according to the GAO's estimation, and drug companies took an average of four months to correct these violations. “The length of time it takes the FDA to issue these letters limits their effectiveness,” the report stated.

Even after a letter is issued, prolonged negotiation between the agency and the company may take place, and “corrective action may not have always occurred in a timely manner,” according to GAO's audit.

If the drug company is cited for a violation and fails to correct its promotional activities, the FDA is supposed to refer the violation to the Department of Justice for enforcement action. The GAO found that none of the 42 violations cited in the regulatory letters in 2003 to 2007 were turned over to the Department of Justice. The agency claimed that it did not take this action because drug companies complied with the agency's requests. However, the report cited examples to show that “[the regulatory letters] do not prevent drug companies from repeatedly disseminating violative promotional materials.”

During the same period, the Department of Justice filed a number of civil and criminal cases against drug companies for alleged off-label promotional activities and reached 11 settlements that amounted to hundreds of millions of dollars (Psychiatric News, February 2, 2007, and November 16, 2007).

The GAO's report, “Prescription Drugs: FDA's Oversight of the Promotion of Drugs for Off-Label Uses,” is posted at<www.gao.gov/new.items/d08835.pdf>.▪