Finance ethics committee, big pharma with deep pockets, mafia like arrangements, and a patient with a 40% increase risk of ischemia myocardial events have in common? I will say todays podcast was inspired by a tweet, yes a tweet from Dr. john Mandrola and he said “I am embarrassed to have not (really) known the details of the rosiglitazone affair. Teaching this to learners has to be 10x more valuable than the krebs cycle. My gosh – talk about lessons to learn. We have to promote more skeptical priors’ He attached a link to a paper titled The rise and fall of rosiglitazone European Heart Journal, Volume 31, Issue 7, April 2010, Pages 773–776 https://academic.oup.com/eurheartj/article/31/7/773/433556 I also will say I did not know the details of the rosiglitazone affair but after spending the last 3 days digging through this paper and the sources to this paper and the sources to those papers and by the end you will know exactly what Finance ethics committee, big pharma with deep pockets, mafia like arrangements, and a patient with a 40% increase risk of ischemia myocardial events all have in common. This was a wonderful summary about rosiglitazone and the scandal of the mafia like drug company hiding and covering up the evidence in related to cardiac events…. For those of you that don’t know or are not medical roseglitizone is a diabetic drug, it part of the glipizide family and although rarely seen on medication this day in are it is a tragic and sickening story for a drug that was once the largest selling diabetes drug in the world. In 2006 sales of the drug reached over $3 billion. So when study came out in 2007 in the New England Journal of Medicine titled “effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes” which was a meta-analysis that sought to find if cardiovascular morbidity and mortality were decreased by rosiglitazone. Ultimately the results showed that those in the rosiglitazone group compared to those in the control group were 43% more likely to suffer a myocardial infarction ((((odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), ))) and a trend towards increase rates of death from cardiovascular causes ((((1.64 (95% CI, 0.98 to 2.74; P=0.06) THAT IS A SHOW STOPPER—the top drug on the market for diabetes bringing in over 3 billion dollars actually causes heart attacks and death Of course GlaxoSmithKline, the maker of the drug came out and said, NO NO NO it is one trial and our drug is just as safe as any other diabetic drug. Hindsight we can all look back and say, “OMG are you kidding me, how did the FDA not step in right away’ and THAT is where the story begins. But in order to get to the beginning of the story to go back to 1998 when troglitazone was the only TZD glitazone on the market. Unfortunately, troglitazone was associated with rare but potentially fatal hepatotoxicity. This is obviously bad publicity in the FDA as well as all diabetics and physicians wanted better option. Insteps rosiglitazone= dysuria over drug was approved by the FDA after 5 trials consisting of just under 3000 patient’s. - https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/21071_Avandia_medr.pdf 2 of the studies were placebo controlled that only lasted 26 weeks 1 study was a double blind comparing RSG with glyburide to just glyburide lasted 52 weeks 1 study was a 26week study looking at the effects of either RSG or placebo added to metformin And the last A 26 week double blind study comparing metformin monotherapy vs RSG monotherapy vs RSG + metformin There you have it- the 5 trials that got RSG FDA approval. Just under 3000 patients and a grand total of 3 yrs TOTAL of data. One of the problems is a duration of these trials. A million one week trials is not equal to one trial that is a million weeks long. The hard outcomes need time to develop. It is like a good play acti(continued)