Oct. 29, 2018
FDA Inspectors Find Serious Violations in High-Risk Human Testing at Minnesota Hospital
Agency Confirms Medical Center Performed Risky Sedation Experiments on Unwitting Emergency Patients
WASHINGTON, D.C. – An inspection by the U.S. Food and Drug Administration (FDA) confirms that a Minnesota medical center violated federal regulations when it subjected unwitting patients to dangerous and unethical human testing, according to documents obtained by Public Citizen under the Freedom of Information Act (FOIA).
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 ketamine compared with other potent sedative medications for management of pre-hospital agitation. The medications 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. It was suspended on June 25.
The FDA inspected the Hennepin County Medical Center’s institutional review board (IRB) – the committee charged with reviewing human research studies – between Aug. 7 and Aug. 23, and evaluated records related to the IRB’s review and approval of the ketamine research and at least two other studies. In a July 25 letter (PDF), Public Citizen and 64 doctors, bioethicists and academics requested that the FDA and the Office for Human Research Protections (OHRP) investigate the medical center.
Public Citizen recently received the initial FDA inspection results in a response to a FOIA request to the agency. The inspection revealed that the Hennepin center’s IRB approved the research without ensuring that the FDA’s requirements for obtaining informed consent of the subjects and for providing adequate safeguards to protect the rights and welfare of vulnerable subjects were satisfied.
Public Citizen, joined by two bioethicists at the University Minnesota, sent a follow-up letter (PDF) today to the FDA and OHRP that highlighted the key observations made by FDA inspectors, noting that they confirm the allegations made in Public Citizen’s July 25 letter to the agencies.
The new letter commended the FDA for taking the July 25 complaint seriously and promptly conducting an inspection of the Hennepin center’s IRB. It went on to blast the medical center as being clearly incapable of protecting human subjects and called for a suspension of research at the medical center.
“The FDA’s inspection reveals that the Hennepin center’s IRB appears to lack even a basic understanding of key federal regulations for the protection of human subjects,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “It is imperative that the FDA and OHRP take immediate steps to ensure the protection of subjects who otherwise will be endangered by participating in high-risk research at the center.”
Public Citizen is demanding that the agency impose severe sanctions on the Hennepin County Medical Center for the serious ethical and regulatory lapses that occurred during the oversight of the ketamine trials and other studies.
The letter also urged the FDA and OHRP to require the Hennepin center to develop a plan to inform each subject whose rights were violated by being enrolled in any clinical trial without appropriate informed consent about their participation in the research, the nature of the regulatory and ethical lapses that occurred and the steps that the center has or will take to redress these violations.