NCPA - National Center for Policy Analysis

New Drugs' Doses Often Lowered for Safety Reasons

October 18, 2002

Establishing recommended dosing regimens has always been a difficult aspect of drug development. Despite spending considerable time and expense to test new drugs seeking Food and Drug Administration approval, drug makers frequently, and increasingly, must reduce the recommended drug dosages after new drug treatments are approved.

The initially recommended dosage of prescription drugs is often twice that needed for safe and effective use in clinical practice, according to two new studies of drugs approved by the Food and Drug Administration (FDA) during the 1980s and 1990s.

  • One study found 115 instances in changes of dosage of which 60 percent were decreases.
  • Another study found that of 354 label changes for new drugs, recommended dosages of 21 percent of the drugs were later changed -- 70 percent of the changes were decreases for safety reasons.
  • Drugs approved in the late 1990s (1995-1999) were three times more likely to experience a dosage change than drugs approved in the early 1980s (1980-1984).

The drug industry commonly launches phase III trials testing the experimental drug at or near the maximum tolerated doses established in phase I and II studies.

The increasing frequency of changes, independent of therapeutic group, may reflect intensified post-marketing surveillance. One implication of the findings of both studies is that more research on the process of drug dose selection is needed to help ensure that patients get the optimal dose prior to seeking FDA approval.

Source: Joan Stephenson, "New Drugs' Dosages Often Too High," Journal of the American Medical Association, October 2, 2002.

Abstracts of studies:


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