Off-Label Prescriptions – Is FDA's Regulation Sluggish?

Off-label use of medicines, though acceptable, is at times still controversial in the medical world. Sometimes the off-label usage is really warranted, at others times it is rarely warranted. But how efficient is the US food and pharmaceutical drug regulator, “the FDA,” in forestalling inappropriate promotion of off-label drug use?

The well-known phenomenon called “Off-label use,” refers to the practice of writing prescriptions for drug usage that's beyond the approved scope of a pharmaceutical drug. Some examples of such usage include SSRI medication (approved for depression) prescribed off-label to treat men suffering from premature ejaculation, Carbamazepine (an anti-convulsant), used to help individuals with bipolar disorder, and Methotrexate or (MTX), which has an approved use in treating choriocarcinoma, if often prescribed to manage an un-ruptured ectopic pregnancy.

In the United States the approval process requires that the Food and Drug Administration (FDA) be convinced of a drug's safety and effectiveness in treating a disease. Once there's enough convincing evidence, the manufacturer and the FDA formulate relevant language for the drug's label.

The following figure presents the frequency of violations.

However, recently a report compiled by the Government Accountability Office (GAO) brought out the fact that the FDA takes about 7 months to send warnings to pharmaceutical companies promoting potentially harmful for off-label uses of medicines. And it takes yet another 4 months for these companies to take corrective action on the violations.

The prevalence of off-label prescriptions can be assessed by the fact that more than 20 percent of prescriptions for 100 most commonly used drugs were found to be for off label use. Further, 60 percent of randomly selected drug prescriptions were again found to be for off-label use.

So, is the FDA sluggish in regulating undesirable off label use promotion?

Experts believe that it might be to quite an extent, due to the following reasons:

1. It takes about 7 – 11 months on an average to address violations.

2. The FDA doesn't specifically monitor off-label promotion. Rather, it's just a part of a larger number of oversight activities for combating all promotional violations. Further, not all submissions to the agency are scrutinized, hence there's a greater chance for violations bypassing the filter.

3. Its capacity to monitor is not at par with the high volume of materials submitted to it (it received 68,000 final submissions in 2007 itself). For instance, the FDA is only able manage a fraction of the thousands of continuing medical education (CME) activities each year, some of which include complaints from doctors to identify off-label promotions in the form of unsolicited statements from sales persons.

The chart below depicts the increasing caseload of the FDA

4. It doesn't keep a tab on all submissions, or the status of reviews supporting off label use, which gets in the way off regulating potential violations.

5. There isn't a standardized tracking system to manage the reviews.

6. Some violations by their very nature are difficult to track, such as the violative conversations between physicians and pharmaceutical drug sales representatives.

The following picture shows the percentage share of each of the target audiences.

While on one hand the FDA's Sentinel Initiative is a great program, the recently highlighted inadequacies of the system regulating off-label promotion of drugs doesn't seem to be encouraging. On the whole it seems that FDA might need to consider a much needed review of the system aimed at addressing unauthorized off label drug promotion, whether it is for conventional drugs or alternative medicines.