Nissen’s Prescience of the Veterans Administration Diabetes Trial
Without ever having read the (at that time) unpublished results of the Veterans Administration Diabetes Trial (VADT), “Dr. Nissen scoffed at the analyses” of safety of rosiglitazone (Avandia, GlaxoSmithKline) before it had even been presented.1
“The VADT trial provides no useful insights into the cardiovascular safety of rosiglitazone,” Dr. Nissen said in an email.
“Approximately 80% of patients in both the intensive and standard treatment groups received rosiglitazone [Avandia; GlaxoSmithKline].2 Therefore, a statistical analysis of the safety of this drug is not possible from VADT,” he said. “Any assertion that VADT demonstrates the safety of rosiglitazone is statistical nonsense.”1
Oops, Dr. Nissen!
Actually, it is quite possible, inspite of Dr. Nissen’s statistical pontifications.
The Veterans Administration Diabetes Trial was designed to evaluate the effects of intensive and conventional glucose control for diabetes,3 not to compare drug regimens.4 However, after Nissen and Wolski’s original meta-analysis,5 the investigators “agreed to conduct” the “specific analysis of events with rosiglitazone” with their data.1
Dr. Nissen “scoffed at the analyses Moritz reported,” which showed statistically “significantly reduced rates of cardiovascular events with rosiglitazone.” Simply comparing the intensive with the conventional glucose control arms would have revealed nothing about rosiglitazone, since most of the patients in each arm received that drug at some point, but that is not what Mr. Moritz did.4
In my next post, I will explain how the Veterans Administration Diabetes Trial analyses of rosiglitazone’s safety were conducted and what they showed.
© 2014 Myron Shank, M.D., Ph.D.6
1 Gever John. ADA: VA Diabetes Trial appears to vindicate rosiglitazone (Avandia) safety. MedPage Today June 8, 2008. http://www.medpagetoday.com/MeetingCoverage/ADA/9749
2 I do not know how Dr. Nissen came up with these numbers. “Almost every VADT patient received rosiglitazone sometime during the study.”3 The percentages steadily trended downward from approximately 90% in both groups, at the beginning of the study, to about 25 and 30% in the conventionally- and intensively-treated groups, respectively, by the study’s end.3 Apparently, there no time when the percentage approximated 80% in both groups, and, during most of the study, it was less than that in both groups.3
3 Moritz Thomas E. Impact of the use of rosiglitazone in VADT. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM224743.pdf
4 Duckworth William, Abraira Carlos, Moritz Thomas, Reda Domenic, Emanuele Nicholas, Reaven Peter D., Zieve Franklin J., Marks Jennifer, Davis Stephen N., Hayward Rodney, Warren Stuart R., Goldman Steven, McCarren Madeline, Vitek Mary Ellen, Henderson William G., Huang Grant D., for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. New England Journal of Medicine 2009; 360:129-139.
5 Nissen Steven E., Wolski Kathy. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. The New England Journal of Medicine 2007; 356:2457-2471.
6 I served: in the speaker program for Takeda Pharmaceuticals America, Inc. and Eli Lilly and Company, Chicago, Illinois, August 7, 1999; as a consultant for Takeda Pharmaceuticals America, Inc. and Eli Lilly and Company, “Current Update and Discussion of the Glitazone Class of Oral Antidiabetics,” January 3, 2001; on Avandia Regional Advisory Panels in Cleveland, Ohio (February 4, 1999), Toledo, Ohio (September 15, 1999), San Juan, Puerto Rico (February 2000), and Beverly Hills, California (April 2000); as a preceptor for SmithKline Beechum, Lima, Ohio (June 23-25, 1999); and in a “Meet-the-Specialist,” SmithKline Beecham, Lima, Ohio, (2000). In 2000, SmithKline Beechum merged with GlaxoWellcome, to form GlaxoSmithKline. Before prescribing rosiglitazone (Avandia, Avandamet, Avandaryl; GlaxoSmithKline) became impractical (and then restricted), I prescribed both it and pioglitazone (ACTOS, ACTOSPlusMet, DuetAct; Takeda).