FDA: Hennepin Healthcare flouted patient safety rules in sedation studies

A board that approves research at Minnesota's largest safety-net hospital failed to follow federal rules designed to protect patients when it fast-tracked studies on powerful sedatives, including ketamine, according to inspection reports from the Food and Drug Administration (FDA).

The Institutional Review Board (IRB) at Hennepin Healthcare expedited approval for at least four studies between 2014 and 2018 that did not require patients to consent beforehand, even though they included a likelihood of using "vulnerable subjects."

This designation refers to patients who need special protections because they can't advocate for themselves and could be easily coerced, such as children, prisoners or people with mental or physical disabilities.

The FDA found that the board approved studies through an expedited process with no evident safeguards to protect the rights and welfare of these patients, and it lacked any written policies for making sure such safeguards exist.

The reports prompted consumer advocacy group Public Citizen to ask the FDA and Office for Human Research Protections in a letter Monday to impose sweeping sanctions on the hospital's research.

"The rules are clear, and it's clear that these studies didn't meet the rules," said University of Minnesota bioethicist Carl Elliott, who signed Public Citizen's letter.

Thomas Hayes, a spokesman for Hennepin Healthcare, said the FDA reports are not final and the hospital has formally responded to the inspections. Researchers halted some of their work months ago, following a Star Tribune report about the no-consent research that drew criticism of the hospital by the public and elected officials.

Hayes said Monday that Hennepin Healthcare did not order a suspension of studies; he said researchers chose to do so at the request of hospital leadership.

In June, the Star Tribune reported on a draft study by Minneapolis civil rights investigators that questioned whether city police officers overstepped their roles in urging paramedics to sedate people with ketamine.

Investigators said the behavior raised concerns over whether sedation was necessary, particularly in cases when the person didn't seem to be a danger to themselves or others, "given the immediate effects on breathing and heart function that the drug induces."

Hennepin Healthcare researchers later enrolled those sedated with ketamine into a drug study comparing the sedative to a similar one called Versed. Researchers gave the patients a waiver to opt out of the study, but did not ask for consent before administering the drug.

Hennepin Healthcare leadership acknowledged in June the need for more transparency and community engagement. It also defended the research, emphasizing the lifesaving value of sedatives in emergency situations involving severely agitated people. Paramedics used the drug only when it was medically necessary, and the hospital examined the data afterward, they said.

Following criticism of the study, which Hennepin County Commissioner Peter McLaughlin compared to the infamous Tuskegee experiment, the hospital announced June 25 it would pause the ketamine study and all other research with a similar consent policy, called a"waiver of consent," and ask a state regulatory board to conduct a review of cases of ketamine use.

It would also consult with a national expert on the hospital's research protocols and look to practices from other health care systems. These reviews are ongoing, Hayes said.

The FDA inspectors' findings appear to contradict statements from Dr. William Heegaard, Hennepin Healthcare's chief medical officer, who told Hennepin County commissioners in June that the hospital followed all standard research procedure in its sedation studies.

"There is nothing unusual, from a research perspective, occurring at Hennepin Healthcare," Heegaard said at the June 26 meeting. "We are following all the rules and the regulations that govern research at all the other U.S. academic medical centers."

Elliott, who attended the June meeting, disagreed. For expedited review, the Institutional Review Board waives the normal vetting process and pushes approval forward quickly, a measure usually reserved for research with little or no risk, he said.

In July, Public Citizen criticized the hospital's ketamine research and asked the FDA to investigate. Starting two weeks later, two FDA inspectors visited the hospital eight times in August.

Hayes said the FDA's inspection was scheduled as part of an approximately five-year cycle. In a statement, he described the FDA's findings as preliminary and addressed by the hospital in its response.

"We understand our mission includes providing the highest standards of medical care, and also conducting studies that help to continuously improve the health and wellness of our patients," Hayes said in a statement. "We will continue to engage with the community to create a better understanding of proposed and approved research activities that benefit all of us."

Public Citizen's letter to the FDA Monday asks the agency to suspend the Hennepin Healthcare Institutional Review Board's ability to approve studies while the researchers at Hennepin halt human trials, receive new training and agree to inform patients enrolled in the studies in question.

"The medical center's IRB appears to lack even a basic understanding of federal regulations for the protection of human subjects and is clearly incapable of fulfilling its obligation to protect the right and welfare of human subjects," the letter states.

The FDA cites four studies fast tracked by the Institutional Review Board "that do not appear to meet the criteria for exception from informed consent." The studies dealt with vulnerable subjects, but lacked evidence for extra safeguards, the FDA found.

One examined ketamine and the sedative haloperidol from 2014 to 2016. Another compared four sedatives used in the emergency department, from 2017 to June 2018. The reports redact the names of two other studies, which are listed as "paused." One of those cites June 25, 2018, as the pause date, which is the same day Heegaard announced the hospital would suspend its ketamine research.

The inspection report also lists three examples from 2017 of the Institutional Review Board approving research through expedited review, "which did not appear in an FDA list of categories eligible for expedited review, and which had not previously been approved by the [review board]."

Andy Mannix • 612-673-4036