staff respondents about how safety issues are handled (DHHS/OIG, 2003) although senior management has strongly defended controversial actions (IOM Staff Notes, 2005–2006). FDA does not routinely conduct “postmortems” of drug withdrawals as a basis for examining and possibly improving its procedures. Drugs withdrawn from the market have been reinstated by FDA for use with restrictions at the request of the sponsor (see Box 2-6 for summary of this case).

One important issue for FDA and all other stakeholders in drug safety is the limited effectiveness of these regulatory warning tools in promoting drug safety. Although changes in the information provided in a label is a key tool for responding to and communicating new safety information, studies show that many patients are at risk because providers and the patients do not consistently heed labels, including the most serious black box warnings (Lasser et al., 2006).

It is worth underscoring that the fundamental design of the drug approval system described above—separate from the quality of the data that sponsors generate in compliance with it—inevitably puts drugs on the market when safety information is incomplete. The obvious corollary is that the postmarket monitoring system, as well as the premarket review processes, must be as effective and efficient as possible.

BOX 2-6

The Story of Alosetron (Lotronex)

November 1999—FDA advisory committee recommends approval

February 2000—FDA approves Alosetron for treatment of “diarrhea-predominant irritable bowel syndrome” in women

June 2000—FDA advisory committee meeting discusses evidence of serious adverse events and votes to retain the drug on the market

November 2000—FDA and the sponsor meet, sponsor withdraws Alosetron

December 2001—sponsor proposes returning Alosetron to market with restrictions

April 2002—FDA advisory committee recommends return to market with restrictions

June 2002—FDA approves Alosetron’s return to market, with less rigorous restrictions than those recommended by the advisory committee

SOURCE: Moynihan (2002).



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