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Commentary |

Improving Detection of Adverse Effects of Marketed Drugs

Donald F. Klein, MD; Charles P. O'Brien, MD, PhD
JAMA. 2007;298(3):333-334. doi:10.1001/jama.298.3.333.
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Public concern about serious toxicities from marketed drugs approved by the US Food and Drug Administration (FDA) has led to suspicion of both the pharmaceutical industry and the FDA.1 This has caused the FDA to issue severe, black-box warnings about antidepressant use; however, this action may have been taken based on inadequate grounds.2

The central problem is that the current faulty system cannot even detect rare but severe toxicities nor can it detect those that appear late in the use of medication or those that occur during off-label use.3 Furthermore, premarketing clinical trials do not address issues related to possible toxicities due to drug interactions or comorbid illnesses. It is often not recognized that there is no basis from information gained in clinical trials for the original indications that lead to legal off-label use for other indications, nor is the pharmaceutical sponsor responsible for checking on such use. Whether FDA warnings, such as black boxes, that recommend increased monitoring (largely of false-positives)4 or suggest that drug withdrawals actually improve the public health remains unknown.

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