A study just released in the May 1, 2002 issue of the Journal of the American Medical Association1 revealed that the dangers of newly FDA-approved drugs are much higher than initially realized prior to going to market.
"Premarketing drug trials are often underpowered to detect ADRs (adverse drug reactions), and have limited follow-up.2,3 In some cases, drugs are approved despite identification of serious ADRs in premarketing trials."4
The study involved the review of 548 new "chemical entities" that were approved by the FDA between 1975 and 1999. A surprising 8.2 percent (45 drugs) of these received one or more "black box warnings"5 in the Physicians' Desk Reference (PDR), with 2.9 percent (16 drugs) being withdrawn from the consumer market altogether for safety reasons.
Using Kaplan-Myers analyses, this means:
"...the estimated probability of (a new drug) acquiring a new black box warning or being withdrawn from the market over 25 years was 20 percent."
This chilling fact is important for consumers to understand when accepting prescriptions for newly approved drugs. The authors noted:
"Nearly 20 million patients in the United States took at least one of the five drugs withdrawn from the market between September 1997 and September 1998. Three of these five drugs were new, having been on the market for less than two years."6
"Only half of newly discovered serious ADRs are detected and documented in the Physicians' Desk Reference within seven years after drug approval," the researchers found; only half of the withdrawals of unsafe drugs take place in the first two years. The authors specify that their definition of a serious ADR was "conservative, since it was limited to Physicians' Desk Reference black box warnings. We did not consider other labeling changes such as bolded warnings without boxes, 'Dear Health Care Professional' letters, or case reports in the medical literature."
Doctors read black box warnings. Patients, however, rely on their doctors to assess and inform them of possible adverse reactions of certain prescription drugs. Some patients may even take the time to read some of the accompanying literature that comes with their prescriptions, assuming they can read the fine print. And then there are the pharmaceutical ads on TV that have the voice-over spitting out at machine-gun speed at the end of the commercial the potential reactions of taking certain drugs (which sound oddly like the commercial spoofs on "Saturday Night Live").
Taking the findings of this study to heart, perhaps patients should also be warned against taking any prescription for a drug released within the last seven years, particularly those released in the last two years. The study concludes with this warning:
"Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years."
- Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002;287:2215-2220.
- Brewer T, Colditz G. Postmarketing surveillance and adverse drug reactions; current perspectives and future needs. JAMA 1999;281:824-829.
- Thase ME. How should efficacy be evaluated in randomized clinical trials of treatments for depression? J Clin Psychiatry 1999;60(suppl 4):23-31.
- Lurie P, Sasich LD. Safety of FDA-approved drugs. JAMA 1999;282: 2297-2298.
- A "black box warning" in the Physicians' Desk Reference is a heavy-lined box that alerts practitioners to serious risks and "special problems, particularly those that may lead to death or serious injury."
- Wood AJ. The safety of new medicines: The importance of asking the right questions. JAMA 1999;281:1753-1754.