The National Institutes of Health will shut down a controversial industry-funded study of moderate drinking and heart disease after a task force found severe ethical and scientific lapses in the study’s planning and execution, the agency’s director said Friday.
The way NIH officials secured funding for the research “casts doubt” on whether “the scientific knowledge gained from the study would be actionable or believable,” according to the task force’s scathing presentation to NIH officials.
The group examining the Moderate Alcohol and Cardiovascular Health (MACH) Trial also found that, starting in 2013, “there was early and frequent engagement” between NIH officials and the alcohol industry that appeared 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.”
When NIH staffers are “conducting activities that they are trying to hide from other staff,” NIH Director Francis Collins said at the meeting, it is “a flashing neon” sign.
The damning conclusions about the study included that “the nature of the engagement with industry representatives calls into question the impartiality of the process,” the head of the task force, NIH principal deputy director Lawrence Tabak, said at the meeting of the advisory committee.
Researchers who have criticized the study applauded NIH’s decision to terminate it. The decision “is the appropriate response to the egregious violation of NIH policy” by the the National Institute on Alcohol Abuse and Alcoholism, which greenlighted the study, said public health scientist Michael Siegel of Boston University. “NIAAA undermined its own scientific integrity by soliciting and accepting alcohol industry funding to study the health ‘benefits’ of alcohol.” Ending MACH “will help ensure that this fiasco is never repeated.”
The drinking study had raised concerns because NIH officials had solicited funding for the $100 million project from liquor companies, with the money funneled through the private NIH Foundation.
Scientists proposing the study told alcohol executives in 2014 that it “represents a unique opportunity to show that moderate alcohol consumption is safe and lowers risk of common diseases,” in particular heart disease, the New York Times reported. The scientists also told industry officials that the randomized controlled study would offer the “level of evidence [that] is necessary if alcohol is to be recommended as part of a healthy diet.”
Last month, amid those and other ethical concerns, NIH suspended enrollment in the multicenter clinical trial, called MACH15. In March, Collins asked a working group of his advisory committee to examine the study’s design and methodology, as well as whether NIH officials violated NIH policy in pitching the study to the alcohol industry.
The group’s investigation also found that there were so many interactions between the scientist eventually chosen to lead the study, Dr. Kenneth Mukamal of Beth Israel Deaconess Medical Center, and NIH officials that he had “a competitive advantage not available to other applicants” to conduct such a study.
Perhaps worst of all, the working group found that interactions among Mukamal, officials at NIAAA, and the liquor industry undermined the study’s scientific integrity. Those interactions “appear to intentionally bias the framing of the scientific premise in the direction of demonstrating a beneficial health effect of moderate alcohol consumption,” the task force’s report said.
One of NIH’s key principles is to award research funding “competitively,” meaning that only the best proposals receive financial support. In the MACH study, however, the “early” and “sustained” interactions between NIAAA staff and Mukamal gave him an unfair advantage, the investigators found, and “effectively steered funding” to him. NIH said it would take “appropriate personnel actions,” but declined to specify them.
The study also had numerous scientific flaws, the working group found, including too few patients and insufficient follow-up time, with the result that “the trial could show benefits while missing harms.”
Before enrollment in the trial was suspended, it had attracted 105 participants and spent $4 million of NIAAA money.
NIAAA Director George Koob, who joined the institute after the problematic interactions between staff and industry, called the MACH trial “irrevocably damaged,” and agreed that it should be shut down.
In a statement, Beth Israel said it is “deeply committed to ensuring the scientific and ethical integrity of any research study involving our investigators,” adding that Mukamal “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 wake of the decision, Collins said NIH officials would examine other industry-NIH ties to make sure proper procedures have been followed, and seek out even “subtle examples of cozy relationships” that might undermine research integrity.