Public Citizen is calling for the immediate suspension of a large NIH-sponsored trial comparing blood transfusion strategies after heart attacks. should be halted "because of potentially serious ethical violations," said the consumer advocacy group in sent to the Office for Human Research Protections and the VA's Office of Research Oversight.
The MINT trial started earlier this year in April and is expected to be completed in 2021. The trial plan calls for 3,500 hospital patients with acute MI who have blood counts below 10 g/dL to be randomized to either a liberal or restrictive transfusion strategy with red blood cells. The primary endpoint is the composite outcome of all-cause mortality or nonfatal MI at 30 days.
Public Citizen claims that the trial is unethical and fails to adequately protect patients enrolled in the trial. They say that the consent form does not fairly describe the trial or explain that the strategies are experimental. Further, the trial protocol does not supply important information that would enable institutional review boards to adequately assess the trial.
"One of the most troubling ethical lapses in the MINT trial is the failure of the consent form to fully disclose to potential subjects the possible risks of using a restrictive blood transfusion strategy," said the director of Public Citizen's health group, Michael Carome, MD, in. "A reasonable person who is considering enrolling in this trial certainly would want to know about prior research results that strongly suggest that use of a restrictive strategy in heart attack patients increases the chances of dying or having another heart attack, and yet the consent form makes no mention of these risks."
Asked to respond to the Public Citizen letter, MINT principal investigator Jeffrey Carson (Rutgers) provided the following statement:
The Myocardial Ischemia and Transfusion Trial seeks to answer an important question about the optimal amount of blood transfusion that we give to patients with low red blood cell counts who have had a heart attack. Previous small trials do not provide adequate data for accurate predictions, which is why the NIH funded this high-quality large trial. The health and safety of our participants is our top concern. Our protocols and processes have been reviewed by more than 35 institutional review boards across the country, as well as the Data Safety Monitoring Board, which is an independent organization comprised of physicians and ethicists. Each board, independently, has approved it.
Carson was also the first author of which suggested that the more restrictive transfusion strategy might actually be beneficial.
Bob Harrington (Stanford) is not involved in the trial but said he has "been interested in the topic for many years." He said that "a well done randomized trial is long overdue. The data (mostly observational and some small trials) suggest that a restrictive approach is preferred over a more liberal transfusion strategy. But it is far from definitive and certainly the level of evidence thus far does not obviate the need for a well-done RCT."
Harrington pointed to the wide variation in clinical practice in this area. "There is no clear answer," he said. "The possible benefit of the restrictive strategy is a hypothesis and the reason that we do randomized controlled trials. Certainly, a careful interim monitoring plan is important and I assume that the NHLBI, as the sponsor, has established one, as they typically do."