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FDA committee urges tight restrictions on rosiglitazone

BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c3862 (Published 16 July 2010) Cite this as: BMJ 2010;341:c3862

More about FDA's advisory meeting on rosiglitazone

Your readers may be interested in additional background concerning the recent US Food and Drug Administration (FDA) advisory committee meeting on rosiglitazone, reported by BMJ on 16 July.(1) Intense controversy has surrounded the question of cardiovascular safety with rosiglitazone since the May 2007 publication of a meta-analysis of randomized controlled trials by Nissen and Wolski, which reported a statistically significant 1.43-fold increase in acute myocardial infarction risk with the drug.(2) Two months later, the FDA convened a joint meeting of its Endocrine-Metabolic and Drug Safety advisory committees to deliberate on the issue. The committee voted 20-3 that rosiglitazone increased the risk of acute myocardial ischemia and 22-1 that rosiglitazone should continue to be marketed because its benefits exceeded its risks, without ever describing these benefits or explaining how they exceeded the drug's adverse cardiovascular risks.(3)

In July 2010, FDA convened another meeting of the same two advisory committees to consider again the cardiovascular safety and fate of rosiglitazone.(4) In an unprecedented move, FDA's Center for Drug Evaluation and Research (CDER), which originally approved rosiglitazone and has defended its continued marketing, invited not only the current members of these two committees to attend the 2010 meeting, but also invited all members from the 2007 meeting, even though they were no longer active members of either committee. Of the 32 advisors who voted on the question of rosiglitazone's future at the 2010 meeting, 15 (47%) attended the 2007 meeting and at that time, all of these voted that rosiglitazone remain on the market.

The addition of these advisors as voting members for the 2010 advisory committee meeting substantially biased the results of the vote on whether rosiglitazone should be withdrawn from the market (table). Committee members considering rosiglitazone's marketing status for the first time were 4.4-times (95% confidence interval 1.1-17.0; p=0.01) more likely to vote that rosiglitazone be withdrawn from the market than were members who had voted previously that rosiglitazone remain on the market.

By inviting members from the 2007 meeting to participate in the 2010 advisory committee meeting, CDER biased the outcome of the 2010 vote in favor of rosiglitazone remaining on the market in some form. Had the 2007 committee members not been invited to attend, the resulting vote would have been 10 (59%) of 17 in favor of rosiglitazone withdrawal, with an additional 3 in favor of restricted distribution. The views expressed are the authors' and not necessarily those of the FDA.

References

1. Roehr B. FDA committee urges tight restrictions on rosiglitazone. BMJ 2010; 341:c3862, doi: 10.1136/bmj.c3862 (Published 16 July 2010).

2. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356(24):2457-71.

3. Joint meeting of FDA's Endocrine-Metabolic and Drug Safety advisory committees, July 30, 2007. Meeting materials and transcript available at: http://www.fda.gov/ohrms/dockets/ac/cder07.htm#DrugSafetyRiskMgmt. Accessed July 27, 2010.

4. Rosen CJ. Revisiting the rosiglitazone story-lessons learned. N Engl J Med 2010; 10.1056NEJMp1008233.

Competing interests: None declared.

Table. July 2010 Food and Drug Administration advisory committee vote on the question of market withdrawal of rosiglitazone, by whether advisor had previously voted to keep rosiglitazone on the market.

Competing interests: No competing interests

02 September 2010
Graham
Medical Officer
Kate Gelperin, medical officer, FDA
US Food and Drug Administration10903 New Hampshire Ave., Silver Spring, MD, 20993, USA