July 25, 2018
FDA, OHRP Must Probe Unethical, High-Risk Human Testing at Minnesota Hospital
Hennepin County Medical Center Performed Risky Sedation Experiments on Unwitting EMS Patients; Most Recent Trial Is on Hold
WASHINGTON, D.C. – The U.S. Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP) must immediately investigate two prospective clinical trials that involved testing the dangerous general anesthetic ketamine and powerful sedatives on patients without their consent, Public Citizen and 64 doctors, bioethicists and academics said today in a letter (PDF) to the two agencies.
As first reported by the Star Tribune and described in the medical journal Clinical Toxicology and other publicly available documents, researchers at Hennepin County Medical Center failed to obtain consent from test subjects for high-risk clinical trials that involved testing the safety and effectiveness of the ketamine compared with other potent sedative drugs for management of pre-hospital agitation, which were injected into the subjects by Hennepin County emergency medical system paramedics.
The first trial, which began in October 2015 and ended in September 2016, compared ketamine with the schizophrenia drug haloperidol and involved 146 unwitting subjects. That trial found that ketamine was much more likely to cause serious adverse events than haloperidol. Notably, subjects receiving ketamine were 10 times more likely to have breathing problems that required placing a breathing tube in the subjects’ tracheas than those receiving haloperidol.
The second trial, which compared ketamine to midazolam, began in August 2017 – well after results of the first trial demonstrating ketamine’s harms were known to the researchers – and was supposed to involve up to 420 subjects.
Eligibility for each trial was determined by paramedics based on the degree of a patient’s agitation. But the trials used a broad definition of “severe agitation,” which likely resulted in some subjects receiving these powerful drugs when they otherwise would not have. In addition, whether subjects received ketamine or the other drug being tested was based on the month in which a subject was enrolled, not by a health care professional’s judgment of what was best for the patient.
“The use of ketamine in particular made these experiments high-risk,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “Ketamine can cause severe airway obstruction, interfering with breathing. In fact, before the first trial testing ketamine and haloperidol began, some of the trials’ researchers had published an article about the dangers of using ketamine for agitation and advised that the drug should be used only in patients with the most profound levels of life-threatening agitation, not those with lesser degrees of agitation, as was case in both of these trials.”
Following the Star Tribune’s revelations, Hennepin on June 25 suspended the clinical trial testing ketamine and midazaolam. The hospital has aggressively defended these trials and has misrepresented them as “observational studies” involving minimal risk, Public Citizen’s letter said.
Documents reviewed by Public Citizen showed that both trials involved more than minimal risk and, as a result, failed to comply with key requirements of FDA and U.S. Department of Health and Human Services regulations for the protection of human subjects as well as basic ethical requirements.
“It’s hard to say what is worse: the sheer number of human subjects forcibly injected with ketamine who wound up needing to be intubated because they could no longer breath on their own, or the fact that these subjects were enrolled in high-risk experiments without their consent,” said Dr. Carl Elliott, a professor at the Center for Bioethics at the University of Minnesota and one the letter’s co-signers.
“The regulatory and ethical lapses in the oversight and conduct of these trials reflect colossal failures of the Hennepin County Medical Center’s human subjects protection program,” added Carome. “The failures extended from the researchers to the institutional review board that approved the trials to senior institutional officials. The FDA and OHRP must promptly find out whether there are other trials ongoing at this medical center with similar lapses.”