Doctors Violated FDA Regulations When They Performed Risky Sedation Experiments on Unwitting Patients
WASHINGTON, D.C. — The U.S. Food and Drug Administration (FDA) should promptly initiate serious enforcement proceedings — specifically, a formal process called disqualification — against two researchers at Hennepin County Medical Center (HCMC) in Minneapolis, Minn. who repeatedly and deliberately violated agency regulations intended to protect human subjects Public Citizen said today in a petition to the agency. The doctors conducted a series of clinical trials that tested the dangerous general anesthetic ketamine and powerful sedatives on agitated patients without their consent.
The consumer watchdog group also asked the FDA to take similar harsh action against the HCMC institutional review board (IRB) for violating federal human subjects protection regulations by approving these trials without ensuring that informed consent requirements for such experiments were implemented.
“The pattern of repetitive egregious violations by the HCMC researchers and IRB over a four-year period that was thoroughly documented by the FDA demand the most serious punishment to hold those responsible accountable and to deter similar serious noncompliance by others,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “A slap-on-the-wrist approach for violations that significantly endangered the health and safety of human subjects and violated their rights will not suffice.”
Public Citizen also demanded that the FDA direct HCMC to contact the more than 1,700 patients who were unwittingly enrolled in unethical experiments and inform them that their rights were violated and their health was potentially endangered by the medical center’s researchers.
The regulatory violations involved four separate clinical trials conducted from 2014 to 2018. Two trials led by Dr. Jon B. Cole compared the safety and effectiveness of ketamine to either haloperidol or midazolam for treating patients with agitation in the community setting, and two led by Dr. Lauren R. Klein assessed the relative safety and effectiveness of four sedating drugs — haloperidol, midazolam, olanzapine and ziprasidone — in patients with agitation in the hospital emergency department setting.
Prompted by a July 2018 complaint letter from Public Citizen and 64 doctors, bioethicists and academics, the FDA in August 2018 conducted an inspection of the HCMC IRB’s records related to the review and approval of Cole’s and Klein’s clinical trials. Then, in April 2019, the agency inspectors examined Cole’s and Klein’s research records for these trials. Serious regulatory violations observed during these inspections were detailed in FDA inspection reports and in subsequent warning letters that the agency sent to Cole and Klein in May of this year.
The findings described in FDA inspection documents and warning letters affirmed the allegations detailed in Public Citizen July 2018 complaint letter to the FDA and OHRP. The FDA found that both Klein and Cole had conducted their clinical trials without having submitted an investigational new drug application (IND) to the agency. An IND is a detailed written request to the FDA to obtain authorization from the agency to administer experimental drugs to humans in a clinical trial.
The FDA’s warning letters found that both Cole and Klein each had previously submitted INDs to the FDA to conduct clinical trials that were “substantially similar” to the trials of the same experimental drugs that they subsequently conducted. However, the submitted INDs had been withdrawn (in the case of Dr. Cole) or placed on hold (in the case of Dr. Klein) because of serious deficiencies that posed unacceptable risks of harm to patients eligible to enroll in the proposed trials. Shockingly, according to the FDA, both Cole and Klein then proceeded to repeatedly conduct substantially similar clinical trials testing the same experimental drugs without submitting an IND and without addressing the FDA-identified deficiencies that posed an unacceptable risk to subjects.
Additionally, the FDA found that both researchers and the HCMC IRB failed to comply with FDA regulations requiring informed consent for clinical trials. FDA inspectors also cited HCMC IRB for failing to ensure that additional safeguards were implemented in the four trials to protect subjects considered to be vulnerable to coercion or undue influence.
“There is clear evidence that Cole and Klein deliberately sought to circumvent the FDA’s IND and informed consent requirements for clinical trials,” said Carome. “The case for the FDA disqualifying them and the HCMC IRB is overwhelming.”
Under the disqualifications sought by Public Citizen, Cole and Klein would be prohibited from conducting clinical trials testing experimental drugs or devices for a specified period of time. Likewise, disqualification of the HCMC IRB would effectively make it ineligible to review such FDA-regulated clinical trials.
Read the petition here.