Trial Put Cardiac Patients’ Safety at Risk Without Proper Consent
WASHINGTON, D.C. – Substantive changes have been made to the protocol and consent forms for a clinical trial sponsored by the National Institutes of Health (NIH) in response to a complaint filed by Public Citizen over potentially serious ethical violations, the U.S. Department of Health and Human Services (HHS) said in a letter delivered to Public Citizen on Monday.
HHS’ Office for Human Research Protections (OHRP) and the U.S. Department of Veterans Affairs’ (VA) Office of Research Oversight (ORO) disclosed the changes to the NIH-funded Myocardial Ischemia and Transfusion (MINT) trial in response to Public Citizen’s August 1, 2017, letter that called for the trial’s immediate suspension.
The MINT trial involves randomly assigning patients suffering heart attacks and anemia to one of two blood transfusion strategies. Some are assigned to a “liberal” strategy in which they are transfused sooner at higher red blood cell (RBC) levels, and others are assigned to a “restrictive” strategy in which they are transfused only when they hit a significantly lower RBC level. Researchers then will measure how many subjects die or have another heart attack within 30 days. The trial, which began last year and is set to end in 2021, will involve 3,500 people at several dozen institutions throughout the U.S. and Canada. Prior studies already strongly suggest that a restrictive transfusion strategy is more likely to lead to further heart attacks and death than a liberal strategy.
“One of the most troubling ethical lapses in the MINT trial previously had been the failure of the consent form to fully disclose to potential subjects the possible risks of using a restrictive blood transfusion strategy,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “We are pleased to see that that the OHRP and ORO required changes that correct this ethical lapse and that address many of our other concerns.”
Based on a review of the MINT trial’s protocol, sample consent forms and background information, Public Citizen last year was concerned that the trial lacked adequate protections for its human subjects and violates basic ethical principles:
- The restrictive transfusion strategy may put the subjects’ health and lives at unacceptable risk;
- The trial protocol failed to provide key information – including a description of current usual care blood transfusion practices for patients with heart attacks who are hospitalized at the institutions that are to enroll subjects – that an Institutional Review Board (IRB) would need to determine whether the study meets approval criteria; and
- The sample consent form for subjects failed to adequately describe the purpose of the research, the risks of the trial and whether the transfusion strategies being tested are experimental.
According to the June 7, 2018, letter from the OHRP and ORO, after receiving Public Citizen’s August 2017 letter, OHRP and ORO staff spoke with personnel at the NIH about the MINT trial and. As a result, both the protocol and consent form for the trial have undergone a number of changes, including:
- Revising the protocol to better describe current usual care for transfusing patients having acute heart attacks;
- Adding to the trial protocol a new requirement that a potential subject may not be enrolled unless the person’s attending physician, with expertise in cardiovascular care, believes that both of the transfusion strategies are consistent with good medical care for the subject as determined by the physician’s clinical judgment; and
- Adding to the subject consent form a more appropriate description of the purpose of the trial and a description of the possible risks of the restrictive transfusion strategy.
The OHRP and VA also noted that all IRBs reviewing the trial were given a copy of Public Citizen’s letter prior to reviewing the revised protocol and consent form documents.
In the past four years, Public Citizen has submitted five formal complaints to the OHRP about unethical clinical trials, but until Monday, had not received substantive responses from the agency for any of them.