August 1, 2017; Miami Herald
Dr. Michael Carome, Director of the Health Research Group division of Public Citizen, a nonprofit consumer advocacy group, criticized a National Institute of Health (NIH) heart attack study in a letter to the U.S. Department of Health and Human Services’ Office for Human Research Protections and the U.S. Department of Veterans Affairs’ Office of Research Oversight. Dr. Carome contends that the new clinical trial “should be halted because it fails to adequately protect human subjects and doesn’t satisfy basic ethical requirements.”
Quoting from the letter, the Miami Herald wrote last week that the study “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.” The study compares two transfusion strategies for heart attack patients with anemia—liberal transfusions, or “transfusion whenever their hemoglobin level falls below 10 grams per deciliter,” and restrictive transfusions, “only when their hemoglobin level falls below 8 grams per deciliter.” Researchers then wait and see “how many subjects in each group die.”
The study, the Myocardial Ischemia and Transfusion Trial, or MINT, is being conducted among 67 medical institutions across the United States and Canada. The principal Investigator is Dr. Jeffrey L. Carson of Robert Wood Johnson Medical School in New Brunswick, N.J. According to the website, the study will “enroll 3500 hospitalized patients diagnosed with myocardial infarction who are anemic (have blood counts less than 10 g/dL) to receive either a liberal or a restrictive transfusion strategy.”
An NIH analysis of 16 randomized trials comparing liberal and restrictive transfusion strategies for heart attack patients found a higher risk of death and major cardiac events associated with a restrictive approach.
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A pilot study for the MINT trial published in the American Heart Journal in June 2013 also suggested that patients were more likely to die from a restrictive approach compared with a liberal one. Of the 110 patients recruited for the study, seven died after a restrictive strategy compared with one who died after a liberal approach.
Dr. Carome censures the MINT Protocol and the patient consent form for failing to inform patients of “the risk of death, repeat heart attack or cardiac surgery as a result of participating in the study.”
To recap: What’s being tested here is whether the restrictive transfusion strategy is more likely to lead to death or other serious harm than the liberal strategy. By signing up for this study, participants are volunteering to potentially join a group where what’s being measured is how many more participants die. What’s more, prior studies have led Dr. Carome to the conclusion that it’s already known that the restrictive strategy leads to more deaths, so the people joining the study are placing their lives on the line to confirm something that’s already been shown, with no evidence that either strategy will lead to an outcome that’s better. And “the consent form is completely silent on that.”
Carome’s argument suggests that the information needs to be clearly stated in both protocol and patient consent forms as per the Belmont Report, HHS regulations at 45 C.F.R. § 46.111(a). The solution to this may be to create a more explicit patient consent form and protocol before beginning the study to meet the requirements of the Belmont Report.
William Allen, “a University of Florida medical ethicist who reviewed Public Citizen’s letter to federal regulators at the Miami Herald’s request,” said, “Well, that’s pretty vague. It doesn’t clearly say they’re trying to figure out which one results in less death and heart attacks in the next 30 days.”
Carome’s criticism may be one reason behind the recent withdrawal of participation by Geisinger Medical Center. It has not been determined if other medical institutions are considering withdrawal of support.—Suja S. Amir