July 2018

Last year, the National Institute on Alcohol Abuse and Alcoholism, part of the federal National Institutes of Health, laid out plans for what is a rarity in the realm of public health: a high quality clinical trial. The “Moderate Alcohol and Cardiovascular Health Trial,” known as MACH15, was to be randomized so that some subjects would be selected to drink and some would not. It would follow participants “prospectively,” over time, not retrospectively. And in the end, the results were to be adjudicated by evaluators blinded to which subjects had been instructed to drink and which to abstain. The goal was an assessment of the effect of alcohol consumption on cardiovascular health. 

The methodologic problems of the MACH15 trial’s design are considerable. How the outcome measures ever passed muster defies logic.

But last month, the National Institutes of Health took the unusual step of shutting down one of its own clinical trials — a $100 million dollar experiment gone wrong. The announcement followed an internal investigation, prompted by a dogged New York Times report, that uncovered inappropriate interactions between the alcohol industry (Anheuser-Busch InBev, Heineken, and others) and the NIAAA in the execution of MACH15. 

Here’s how it was supposed to have worked: Volunteers aged 50 or older with either substantial cardiac risk factors or existing heart disease were to have been randomly assigned to either abstain from alcohol completely or to consume precisely one alcoholic beverage per day. They were then to be monitored for cardiovascular health. Investigators were interested in whether the patients assigned one drink per day were more, less, or equally likely to experience a heart attack, stroke, or even die in just six years? This was primary goal of the MACH15 trial. 

In essence, the NIH was making a $100 million gamble that volunteers would portray their alcohol consumption accurately. 

That’s not where the problems ended. In their report, the NIH investigators said they had found that the trial was apparently set up to lean towards “demonstrating a beneficial health effect of moderate alcohol consumption,” and that it was exceedingly unlikely to find that alcohol was harmful, because the trial design ignored some of alcohol’s most notable long-term risks, including cancer and congestive heart failure — the latter of which is linked to alcohol consumption. The eventual study would have under-reported cancer risks simply because, at six years, the trial was too short for those dangers to have caught up to patients who drink. But neglecting to include heart failure as an outcome of interest in a trial assessing cardiovascular health of alcohol is a far more flagrant oversight — akin, perhaps, to a study assessing the health risks of sugar intake in which researchers failed to ask whether patients developed diabetes. How the outcome measures of MACH15 ever passed muster defies logic, but in a statement attributed to Dr. Kenneth Mukamal, the study’s principal investigator, and supplied by his hospital’s public affairs office, he said the protocol was approved by “three external scientific panels and by ten institutional review board.” 

“Most trials undertaken today are destined to produce a certain conclusion through designs that are manipulated just enough to almost guarantee a result without losing their integrity.”

Perhaps what sets MACH15 apart is not what it did, but who did it. The alcohol industry, while powerful, is far less experienced in the realm of biomedical research than large pharmaceutical companies who perhaps, by now, know just how to expertly game the research system without breaking the rules outright. Alternatively, it might be that alcohol itself is expected to play by a different set of rules than other would-be medicinal compounds. “Alcohol was never meant to necessarily benefit people, unlike medications,” wrote Florence Bourgeois, an assistant professor of pediatrics and emergency medicine at Harvard Medical School and a faculty member at Boston Children’s Hospital, in an email. “With drugs, pharma can justify their trials and marketing as an attempt to help people in need of medical breakthroughs. But alcohol is generally perceived as harmful to our society, so attempting to promote it on the false grounds of having health benefits doesn’t go over well in the lay media.”  

For complete article  cited 30/7/18