From: Graham, David J [mailto:David.Graham1@fda.hhs.gov]
Sent: Friday, May 28, 2010 3:31 PM
To: Hamburg, Margaret; Sharfstein, JM
Cc: Graham, David J
Subject: TZD study update
Dear Drs. Hamburg and Sharfstein,
Except for a few minor details, we have completed our study comparing the cardiovascular risks of rosiglitazone vs. pioglitazone in Medicare elderly.
With over 227,000 exposed patients, we found that rosiglitazone increases the risk of stroke by 27% (11-44), heart failure by 25% (16-34), death by 13% (4-23), AMI or death by 11% (3-18), AMI, stroke, or death by 14% (7-21), and AMI, stroke, heart failure or death by 17% (12-23). The risk of AMI surviving to hospitalization was increased by 6% (-5 to +17), but not statistically significantly so. We suspect that fewer elderly patients survive their AMI long enough to reach hospital so that AMI/death is a better measure.
The number needed to harm was 59 patients treated with rosiglitazone for one year to produce one excess case of any of our outcomes. This translates to 48,000 excess events attributable to rosiglitazone among patients age 65 years or older between 1999 and June 2009. Given that 62% of rosiglitazone use has been in patients below age 65, the actual national impact is probably 100,000 or more.
JAMA is very interested in our manuscript and we would like to submit it before next Friday, June 4. Gerald Dal Pan, my supervisor is prepared to sign the clearance form (the paper has a disclaimer and does not represent an official FDA position) but won’t unless Dr. Woodcock and Dr. Jenkins approve. He is afraid to act, even though he is the “clearing official.”
My CMS co-authors are also anxious to submit the manuscript and feel that they have a duty to their customers, Medicare patients, to bring these results to public notice in a scientific journal as soon as possible. The idea of being blocked from doing this by a sister Agency is a source of concern to them and to me.
In late 2004, CDER management suppressed the publication of a study I conducted using data from Kaiser California that showed increased AMI risk with rofecoxib. This was done in an effort to downplay the seriousness of their prior poor decision-making in leaving rofecoxib on the market. So you can understand that I am very sensitive to anything that remotely smells like suppression or censorship. I am asking for your assistance in ensuring that we are able to submit our manuscript to JAMA before June 4.
Best regards,
David