Rosiglitazone: A Thunderstorm from Scarce and Fragile Data

Editorials16 October 2007Rosiglitazone: A Thunderstorm from Scarce and Fragile DataCynthia D. Mulrow, MD, MSc, Deputy Editor, John Cornell, PhD, Associate Editor, and A. Russell Localio, PhD, Associate EditorCynthia D. Mulrow, MD, MSc, Deputy Editor, John Cornell, PhD, Associate Editor, and A. Russell Localio, PhD, Associate EditorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-8-200710160-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The U.S. Food and Drug Administration (FDA) has approved many pharmacotherapies for treating diabetes on the basis of the drugs' ability to improve glycemic control. Although preventing adverse macrovascular outcomes, such as myocardial infarction, is a desirable goal for treatment of type 2 diabetes, there is no definitive evidence that any FDA-approved pharmacotherapy achieves such aims (1). Worse, recent meta-analyses suggest that rosiglitazone, a widely prescribed oral hypoglycemic agent, might increase the risk for ischemic heart disease by a small amount. We examine the fragile data underpinning that story and the challenges of summarizing trials with scarce events.Early Storm ...References1. Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147:386-99. LinkGoogle Scholar2. FDA Briefing Document: Joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. 30 July 2007. Philadelphia: GlaxoSmithKline; 2007. Accessed at www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-02-fda-backgrounder.pdf on 1 August 2007. Google Scholar3. Advisory Committee Briefing Document: Cardiovascular Safety of Rosiglitazone. Philadelphia: GlaxoSmithKline; 2007. 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N Engl J Med. 2007;356:2457-71. [PMID: 17517853] CrossrefMedlineGoogle Scholar8. Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, et al. Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med. 2007;357:28-38. [PMID: 17551159] CrossrefMedlineGoogle Scholar9. Rosen CJ. The Rosiglitazone story—lessons from an FDA Advisory Committee meeting. N Engl J Med. 2007;:. [PMID: 17687124] CrossrefMedlineGoogle Scholar10. Diamond GA, Bax L, Kaul S. Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Ann Intern Med. 2007;147:578-81. LinkGoogle Scholar11. Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med. 2007;26:53-77. [PMID: 16596572] CrossrefMedlineGoogle Scholar12. Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med. 2004;23:1351-75. [PMID: 15116347] CrossrefMedlineGoogle Scholar13. Sankey SS, Weissfeld LA, Fine MJ, Kapoor W. An assessment of the use of continuity correction for sparse data in meta-analysis. Communications in Statistics: Simulation and Computation. 1996;25:1031-56. CrossrefGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Disclosures: None disclosed.Corresponding Author: Customer Service, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoUncertain Effects of Rosiglitazone on the Risk for Myocardial Infarction and Cardiovascular Death George A. 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