NIH Pulls Funding for Prospective Trial Exploring CV Effects of Moderate Alcohol Intake

June 20, 2018

The US National Institutes of Health (NIH) is pulling the plug on a randomized trial that had just started and was designed to explore the cardiovascular effects of moderate, regular alcoholic-beverage intake.

NIH withdrew funding for the Moderate Alcohol and Cardiovascular Health Trial (MACH15) because of "concerns about the study design that cast doubt on its ultimate credibility" as well as the partial funding by the alcoholic-beverage industry, it said in a public statement.

Those concerns include possible pro-alcohol bias in its primary endpoint, inadequate attention to potential noncardiovascular alcohol hazards like some cancers, and "irregularities" in the trial's funding-award process.

The statement says the decision by NIH Director Francis H. Collins, MD, PhD, to pull MACH15 funding follows the recommendation of a working group of the NIH Advisory Committee to the Director in its 165-page report published June 15. NIH had suspended enrollment into the trial in May. 

How Industry Money Became Involved

The industry backing had been solicited by employees of the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in violation of NIH policy prior to funding involvement by the Foundation for the National Institutes of Health (FNIH), the NIH said.

FNIH handles private donations supporting NIH research and maintains procedural firewalls to protect against biases distributing research support, the statement said. It noted that the foundation had itself raised $67.7 million for the trial from private donations; the NIAAA had been expected to contribute $20 million.

Those amounts are exclusive of private-sector donations, which the NIH statement didn't tally.

Email correspondence "clearly shows industry interactions and discussions related to the scientific planning of the study that appear to go beyond the norm," according to the working group report, which includes copies of the emails.

"In opposition to NIH policy, NIAAA staff directly engaged with industry representatives, accompanied by extramural researchers, over 2 years prior to the FNIH's involvement, and in a manner that kept FNIH and some members of NIAAA staff in the dark," the working group report states.

That "early and frequent engagement" appeared "to be an attempt to persuade industry to support the project," the report continues.

"The nature of the engagement with industry representatives calls into question the impartiality of the process and thus casts doubt that the scientific knowledge gained from the study would be actionable or believable."

Issues With Trial Design

The report also slammed certain aspects of the MACH15 design, including that it was "inadequately powered to assess long-term safety and global health status."

The trial was to enter a planned 7800 participants at least 50 years old who had at least one alcoholic drink in the past 5 years; they were considered high-risk for a new cardiovascular event by any of several standard measures. Exclusion criteria included evidence for a history of heavy drinking.

Participants were randomized single-blind to an abstention group and a moderate-drinking group, the latter calling for daily intake of one drink containing about 15-g alcohol.  

They were to be followed for an average of 6 years; the trial's starting date of record was February 5, 2018. The primary endpoint was to be a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for angina, coronary or carotid revascularization, or death from any cause.

However, notes the working group report, "The composite primary endpoint does not include heart failure, which is a serious shortcoming. Alcohol consumption is associated with higher risk of heart failure."

Associations between alcohol intake and some cancers are also well-recognized. The working group contends that in MACH15, as it was planned, "There are not enough patients and not enough follow-up time to allow for meaningful assessment of cancer endpoints, so that the trial might show benefits while missing the harms."

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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