A consumer-advocacy group is filing a complaint with the US government about two clinical trials in Minnesota that allegedly gave agitated patients ketamine and other sedatives without their consent, despite evidence that doing so could harm their health.

The trials were conducted by researchers at Hennepin County Medical Center (HCMC) in Minneapolis, Minnesota, between October 2014 and June 2018. In its complaint, the advocacy group Public Citizen in Washington DC alleges that the studies’ organizers and the HCMC’s ethics-review board allowed the trials to proceed without obtaining consent from patients. In both studies, paramedics responding to medical emergencies injected agitated people with either ketamine or another sedative to determine which drug worked fastest. Patients were only notified afterward that they had received a sedative.

Sixty-four doctors, bioethicists and academic researchers have co-signed Public Citizen’s complaint, which the group plans to submit to US Office of Human Research Protection (OHRP) and the Food and Drug Administration (FDA) on 25 July.

“This isn’t even a close call,” says Michael Carome, director of Public Citizen’s health-research group. “This is clearly a prospective, high-risk experiment. This is really just a colossal failure of their program to protect human subjects.”

A spokesperson for Hennepin Healthcare, which operates Hennepin County Medical Center, told Nature that the hospital would not comment on the studies until after ongoing internal and external investigations were complete.

Evaluating risk

The FDA’s ethics guidance for clinical trials typically allows investigational drugs to be used in emergencies without patients’ consent, as long as they are known to be of minimal risk. When assessing the two trials, the HCMC’s internal ethics oversight body, known as an institutional review board (IRB), determined that ketamine fell in this category.

But according to Public Citizen’s complaint, prior studies had suggested that ketamine could have more significant respiratory side effects than other sedatives. The HCMC researchers’ first trial, which enrolled 146 agitated patients, arrived at similar conclusions ¹ . It found that 39% of subjects who received ketamine developed respiratory problems that required the insertion of a breathing tube — compared to only 4% of those who received the sedative haloperidol.

The study also reported that ketamine sedated patients much more quickly than haloperidol did, but that respiratory side effects were most likely to develop in severely agitated patients who received ketamine.

“Exactly how the IRB decided this could be a minimal risk study is baffling,” says Carl Elliott, a bioethicist at the University of Minnesota in Minneapolis, who co-signed Public Citizen’s complaint. US government guidelines define “minimal risk” as the risk experienced in daily life or a routine medical exam.

Second study

In 2017, the HCMC launched a second study of ketamine in agitated patients — enrolling 420 people in a trial that compared the sedative effects of the drug to those of another medication, midazolam. All agitated patients admitted to the hospital during the first six months of the study would receive ketamine, and those admitted during the second six months would receive midazolam.

But the hospital shut the study down in June 2018 after the Minneapolis Star-Tribune revealed that a report from Minneapolis’s Office of Civil Rights found that Minneapolis police had encouraged medical personnel to sedate troublesome patients, including some who were already physically restrained. According to the newspaper, the report also said that in several cases, patients treated with ketamine had to be resuscitated at the hospital after their hearts or breathing stopped. The HCMC halted the trial, pending an internal investigation as well as an independent investigation led by former deputy US attorney-general Sally Yates.

In a statement posted earlier this month on its website, the hospital denies that police could direct paramedics participating in the study to administer sedatives to specific patients. The hospital says that it instructed paramedics that using ketamine or another sedative on a person should be a medical decision.

In its complaint, Public Citizen alleges that paramedics’ decisions were driven by the study’s timeline, not by their clinical judgement. The groups argues that the hospital’s IRB should have required the researchers to obtain patients’ consent and receive clearance from regulatory bodies such as the OHRP and the FDA.

The complaint also criticizes the assessment scale that emergency medical personnel used to determine whether to treat an agitated patient with a drug. The scale had been developed by the HCMC research team, and defines agitation more broadly than the scale normally used by emergency responders when deciding to sedate a patient. Carome says that this means the trial may have included some patients who would not otherwise have received any drug at all.

HCMC spokesperson Christine Hill did not answer questions about Public Citizen's claims. "We are committed to transparency and retaining the public's trust and, to that end, have been participating in ongoing internal and independent outside reviews of research and care protocols,” she told Nature .