Justice deferred on ketamine testing

‘Human guinea pigs’ remain at risk

News Analysis

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Hennepin County Medical Center (HCMC) has continued conducting ketamine trials on patients without their consent after announcing in June 2018 it would stop, according to recent reports from the FDA.

Last year, the public discovered that Hennepin County Medical Center (HCMC) had been sedating patients with ketamine, an anesthetic that has been used as a mood-altering drug and as a date rape drug, as part of its studies. For years, staff collected data without receiving consent or informing patients.

In the trial studies, the HCMC researchers intentionally chose not to inform patients who were involved until after they had involuntarily taken part, effectively violating patients’ rights. The unethical study, discomfortingly similar to the Tuskegee syphilis treatment scandal involving African American men (1932-1972), sparked nationwide controversy.

One would have expected an aggressive response from the medical center, county officials and the City of Minneapolis, followed by corrective measures reassuring the public that this flawed and inhumane practice would never be repeated and holding those responsible accountable.

Unfortunately, a year later no such response has been forthcoming, with new FDA reports obtained by the Star Tribune showing that the medical center continued testing well into November 2018.

Unethical placement

Records show that HCMC conducted a research study comparing the effects of ketamine and haloperidol (Haldol) between October 2015 and September 2016. During that time, 146 people were placed in the study by Emergency Medical Technicians (EMT) who chose patients according to their level of pre-hospital agitation, medically known as “severe acute undifferentiated agitation.”

Based on the study’s requirements, a sedative could be administered if the patient was very anxious, making loud outbursts, making facial expressions that indicated agitation, or if the patient appeared potentially violent.

These subjective criteria gave paramedics a lot of latitude in deciding the level of a patient’ agitation and whether the drug should be administered.

“Considering our society’s bias and misinterpretation of Black people’s behavior, you could see how this could cause problems,” said Michael Friedman, director of the Legal Rights Center.

Beyond subjective criteria, patients were not even aware they were part of the study. According to the public watchdog group Public Citizen, which initially brought attention to issues in the study, the human research “failed to comply with key requirements of Food and Drug Administration (FDA) and Department of Health and Human Services (HHS) regulations for the protection of human subjects.” It failed to “satisfy the basic ethical principles upon which those regulations are founded.”

“Without informed consent, subjects were in effect guinea pigs after the fact and were given a letter after the fact, which did not accurately reflect the nature of the research, which was clearly not minimal risk research,” explained Dr. Michael Carome, director of Public Citizen’s Health Research Group. “It was, in fact, a risky trial in which researchers pre-determined which drug you got for your agitation.”

The hospital claimed it conducted the study without consent because the drug involved “minimal risk.” According to the FDA, “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

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Ketamine dangers

The documented risks and side effects of ketamine are extensive — they include hallucination, loss of memory, respiratory depression, airway obstruction, oxygen desaturation, apnea, and heightened blood pressure and pulse rate. “Ketamine should only be used in the most extreme cases of agitation,” said Dr. Michael Carome, director of Public Citizen Research Group. “Yet [the HCMC research] involved patients who did not have a severe level of agitation.”

Dr. Carome said one of the more serious side effects of ketamine is that it can “block your ability to breathe.” Of the 64 subjects in the HCMC ketamine group, 39 percent were intubated, meaning that the subject had to have medical help in order to breathe. Only four percent in the Haldol group were intubated.

HCMC’s own study showed patients in the ketamine group experienced “adverse events” much more often than in the Haldol group. These “adverse events” included hyper-salivation, emergence reactions (nightmares or delirium experienced by up to 55 percent of people emerging from ketamine intoxication), vomiting, dystonia (uncontrollable muscle spasms), laryngospasm (muscle spasms of the vocal cords), and akathisia (uncontrollable restlessness).

Despite the dangers made apparent in its comparative study of ketamine and Haldol, HCMC doctors commissioned a second one comparing ketamine to the drug midazolam. The HCMC’s Institutional Review Board (IRB) even gave the trial the go-ahead, claiming that all FDA and HHS requirements had been met, particularly the principle of “respect for person.” That study began in August 2017 and was scheduled to continue for a year until it was said to be suspended in June 2018 after media attention and external agencies raised red flags on the study. The studies continued through November 2018, enrolling 874 patients in total, according to FDA documents.

 “How many other ongoing and prior clinical trials conducted by the Hennepin County Medical Center have or had similar serious regulatory and ethical lapses?” asked Public Citizen in a letter to HHS.

Ignoring the crisis

While the hospital has issued an apology for its failure to inform the public about the trials, it continues to deny wrongdoing and even defend its study. This, despite outside experts pointing out a clear violation of the minimal risk standard that would allow such testing or research without prior notice of the patient. And, this, despite the FDA condemning HCMC’s failure to properly protect its human subjects.

HCMC’s Dr. Nick Simpson has even characterized the fallout as a “media crisis,” rather than an ethical crisis. When MSR asked HCMC media representative Christine Hill what it was that motivated this risky research study, she responded, “Patient care!”

While the Minneapolis City Council initially expressed alarm over the issue and promised their constituents an independent investigation, they failed to reach a contract agreement with former acting U.S. Attorney General Sally Yates to take on that task. Council members at the time said the $195,000 price tag was too high and that the money would have to come out of the police budget, which they said was already strained. The proposed investigation remains stalled, if not abandoned.

As of this date, no one has been held accountable, disciplined or fired as a result of putting so many people at risk. The studies, however, have led to at least one federal lawsuit claiming civil rights violations after being enrolled without consent. Brittany Buckley is suing HCMC and Hennepin Healthcare for medical malpractice, negligence and excessive force that resulted in breathing and heart complications.

“Federal regulators need to come down hard on HCMC,” said Dr. Carome. “The failure here represents a systematic failure of HCMC and a systematic breakdown in protecting human subjects.”