Side effects common in new drugs

July 1, 2002

Pharmaceutical Representative

A new study in the Journal of the American Medical Association (vol. 287, no. 17) found that one in five new drugs had adverse reactions, and that the safety of new drugs could not be known until after they had been on the market for many years.

A new study in the Journal of the American Medical Association (vol. 287, no. 17) found that one in five new drugs had adverse reactions, and that the safety of new drugs could not be known until after they had been on the market for many years.

The study found that, out of a total of 548 new chemical entities approved between 1975 and 1999, 10.2% acquired a new black box warning or were withdrawn – 45 acquired one or more black box warnings and 16 were withdrawn from the market. The authors determined that the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%. Of the 81 major changes to drug labeling in the Physicians' Desk Reference (including the addition of one or more black box warnings per drug, or drug withdrawal), half occurred within seven years of drug introduction; half of the withdrawals occurred within two years.

An inaccurate picture?

In an editorial in the same issue of the journal, Robert Temple and Martin Himmel of the Center for Drug Evaluation and Research Policy at the Food and Drug Administration said that the study did not give an accurate picture of how long it took for adverse effects to be detected. "Examining the appearance of black box warnings and withdrawals is a reasonable way to seek out the most important new [adverse drug reactions], so that their implications can be considered," wrote the authors. "Use of the Physicians' Desk Reference to determine the timing of the labeling change is convenient, but does not give an accurate measure; this approach inevitably overestimates the delay between marketing and the labeling event because the Physicians' Desk Reference cannot change between editions, while labeling does change. Although the Physicians' Desk Reference is a widely used reference, important labeling changes are often communicated to physicians by 'Dear Health Care Professional' letters, and, once in labeling, the black box warning appears prominently in drug promotion materials. The use of the Physicians' Desk Reference to estimate time of black box warning appearance will make the warnings added early in the life of the drug seem more delayed than they were, but will not greatly affect the warnings added late."

Concluded Temple and Himmel: "[T]here is reason to believe that some of the more common causes of significant toxicity will be less likely in the future. However, no improvements will completely eliminate the risk of unexpected events. The FDA continues to rely on reporting of [adverse drug reactions] by physicians, other healthcare professionals and others to help uncover these risks as rapidly as possible." PR

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