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NIH ends funding for study of moderate alcohol consumption, CV health
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The NIH announced that it will stop funding a trial assessing the effect of moderate alcohol consumption on CV health due to “concerns about the study design that cast doubt on its ultimate credibility.”
The multicenter, randomized MACH15 trial, led by Beth Israel Deaconess Medical Center, was to investigate the effect of moderate alcohol consumption (approximately 15 g per day) vs. no alcohol consumption on the incidence of new-onset CVD and diabetes in participants without diabetes at baseline. Enrollment began Feb. 5 and was suspended May 10 after 105 of a planned 7,800 participants were recruited, according to a press release from the NIH.
The NIH’s National Institute of Alcohol Abuse and Alcoholism (NIAAA) will end its funding in the next few months “following completion of an orderly closeout,” according to the release.
The NIAAA expected to commit $20 million to the overall project over 10 years, of which $4 million has been spent, and the Foundation of the NIH had raised $67.7 million in private donations, of which $11.8 million has been spent, according to the release, which noted that private-sector funders included Anheuser-Busch InBev (until June 9), Carlsberg Breweries A/S, Diageo plc, Heineken and Pernod Ricard USA LLC.
The recommendation to end funding, made by the NIH’s Advisory Committee to the Director, also noted that “significant process irregularities in the development of the funding opportunities for the MACH funding awards undermined the integrity of the research process,” including concerns about “whether the study would effectively address other significant consequences of moderate alcohol intake, such as cancer,” according to the release.
In its report, the advisory committee stated: “There was early and frequent engagement among [NIAAA staff, select extramural investigators and industry representatives] which appear to be an attempt to persuade industry to support the project. Several members of NIAAA staff kept key facts hidden from other institute staff members and the [Foundation of the NIH]. 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. There were sustained interactions between the eventual principal investigator of the MACH trial and members of the NIAAA leadership prior to and during the development of [funding opportunity announcements] for planning and main grants to fund the program. These interactions appear to have provided the eventual principal investigator with a competitive advantage not available to other applicants, and effectively steered funding to this investigator.”
In addition, the committee wrote: “Interactions among several NIAAA staff and industry representatives appear to intentionally bias the framing of the scientific premise in the direction of demonstrating a beneficial health effect of moderate alcohol consumption. Independent review of the trial plan raised concerns that there are insufficient patients and not enough follow-up time to allow for meaningful assessment of cancer endpoints. The composite primary endpoint does not include heart failure. Thus, the trial could show benefits while missing harms.”
In a statement emailed to Cardiology Today, Jennifer Kritz, spokeswoman for Beth Israel Deaconess Medical Center, wrote that the institution “is deeply committed to ensuring the scientific and ethical integrity of any research study involving our investigators, and we appreciate the working group’s review. Principal investigator Kenneth Mukamal, MD, is an experienced researcher who has led dozens of important studies over his career. We take the working group’s findings very seriously and will review the report carefully.”
In the same email, Mukamal issued the following statement on behalf of the MACH15 investigators:
“The study of the long-term health effects of moderate alcohol consumption is of vital scientific importance. While the health outcomes of moderate drinking have been studied for many years by passive observation, a long-term trial to test its effects — the highest standard of medical evidence — has never occurred. Despite this lack of certainty, the concept that moderate drinking improves heart health has gained wide traction worldwide. Without a randomized trial, physicians, patients, and societies are left to use tenuous, limited, and unconvincing data about its potential risks and benefits.
As investigators, we stand fully and forcefully behind the scientific integrity of the MACH15 trial protocol and team. MACH15 has brought together diverse investigators and centers with outstanding records in the conduct of interventional studies. Every design consideration was carefully and deliberately vetted with no input or direction whatsoever from private sponsors, who have had no contact regarding MACH15 with any study staff member since the trial began. The protocol has been reviewed and approved by three external scientific panels and by 10 institutional review boards.
As is true for all clinical trials, MACH15 cannot address every question that every individual might wish to answer. Nonetheless, the trial is appropriately powered to detect its primary and secondary endpoints of total mortality, cardiovascular disease, and diabetes, the major causes of mortality in the United States and worldwide. The protocol has been made publicly available (https://clinicaltrials.gov/ProvidedDocs/30/NCT03169530/Prot_003.pdf), and it incorporates proven methods used in other trials to capture specific postulated health concerns of moderate drinking, including heart failure and cancer. In accordance with the highest ethical standards and specific human subjects protection regulations, the trial also minimizes the risk-benefit balance for its participants by excluding individuals at highest risk for harm, aiming to prevent adverse events and ensuring the safest possible study for all volunteers.
We appreciate the effort that the NIH has made to study its own processes and remain eager to work with the NIH to address this important public health question. However, we are deeply disappointed that issues raised have led to a recommendation to end the trial and negate the extraordinary efforts of its participants, investigators, scientific and ethics review boards, and many dedicated staff members. We strongly believe that MACH15 has a critically important scientific premise, rigorous design, and highly qualified team and represents the best and perhaps only opportunity ever to gain clear answers to these important questions.”
The NIH stated in its press release that it will “take appropriate personnel actions, but cannot comment on specific personnel matters.”
“NIH has strong policies that detail the standards of conduct for NIH employees, including prohibiting the solicitation of gifts and promoting fairness in grant competitions. We take very seriously any violations of these standards,” NIH Director Francis S. Collins, MD, PhD, said in the release. – by Erik Swain
Disclosures: Mukamal reports no relevant financial disclosures. Collins is an employee of the NIH.