In 2006, an observational study in the New England Journal of Medicine suggested that Trasylol may have had more adverse effects that previously believed. [ Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354:353-365.] [Free Full Text]
The first author of the study testified at a US Food and Drug Administration (FDA) hearing under adversarial circumstances.
Panelists attacked Mangano's methodology, saying he had not sufficiently accounted for the high-risk nature of patients receiving Trasylol.
In a recent interview, Mangano said he was shocked by the panel's harsh reception of his work.
'The whole thing was a set-up,' he said. 'We did not have anything to gain financially by this. We were making an observation about safety.'
Mangano noted that the chairman of the panel, Dr. William R. Hiatt, has written papers underwritten by Bayer, and that three committee members received waivers to vote because of financial interests in drug companies.
'The system is ridiculous,' he said. 'It's all pro-industry. Who's protecting the patient?'
Only after the meeting was it revealed that Bayer had hidden the results of its own study.
Dr. Alexander Walker, a professor at Harvard School of Public Health, said Bayer hired him six months earlier to review an enormous database of 67,000 bypass patients. The study compared the side effects of Trasylol with those of the two other anti-bleeding drugs.
Walker said his analysis matched Mangano's: Trasylol patients seemed to be at increased risk for death, kidney failure, congestive heart failure and stroke.
When contacted by the FDA, Bayer said it had 'mistakenly' neglected to mention the giant study. The company said the data was "preliminary in nature and raised significant questions on the study population, outcomes and methodology."
That response sounds hollow to several advisory committee members still stung by Bayer's behavior. Dr. Michael Lincoff, vice chairman of cardiovascular research at Cleveland Clinic in Ohio, said that several panelists had commented during the meeting on the need for more data.
'At no point did the Bayer folks say, 'It's on its way,'' he said.
Steve Findlay, a panel member and health care analyst with Consumers Union, said Bayer's actions were 'intentional and very disingenuous.'
'Absolutely no one would say it was in the public interest, or the interest of people having heart surgery, for that information not to be made public.'
'Bayer's action is yet another example, and an egregious one, that shows the lack of transparency regarding important data,' Findlay said. 'We need a system that makes all this publicly available.'
Bayer suspended two unidentified employees following the revelation of Walker's study. It also said it was investigating the incident, a review the company says is still under way.
Mangano's final comments were
You just wonder how many heart failures and strokes are going to happen because this drug is still on the market.
But bringing up drug safety issues is not for the weak-hearted. There are a lot of interested parties that go against you. You just keep moving forward.
We have said it before. We will say it again. To make the best decisions about tests and treatments, patients and physicians need access to the best available data from clinical research. Thus, suppressing research data or results is bad for patients and physicians. It also betrays the patients who originally volunteered to participate based on the understanding that their participation would be used to advance science and health care.
Thus, commercial research sponsors (e.g., drug, biotechnology, or medical device companies) who suppress such data are betraying their public trust. If they cannot be trusted not to suppress data that is unfavorable to their interests, they ought to be banned from sponsoring or controlling research on human beings.
Hat tip to PharmaLot.