FDA: Advocate Health Care conducted drug study without patients' consent
FDA warning letter start from website (June 17, 2012)
The letter to Advocate’s institutional review board is dated June 1 and was posted on the FDA’s website this week.
Institutional review boards, or IRBs, are responsible for overseeing research involving human subjects to make sure their rights are protected.
The research project involved emergency room patients undergoing intubation, an emergency procedure in which a tube is inserted down the throat to open the airway.
The study, conducted at Advocate Christ Medical Center in Oak Lawn, originally was designed to evaluate the outcomes for people whose doctors chose to administer a sedative called etomidate.
In approving the study in December 2006, the review board determined the research did not require patient consent because it involved reviewing files of people already treated.
But in July 2007, the clinical investigator proposed that human subjects be randomly selected to receive one of two drugs, etomidate and midazolam.
The board approved the modification in September and allowed the clinical investigation to continue without lifting the waiver on obtaining informed consent.
FDA official Dr. Leslie K. Ball wrote in the warning letter that the new study design turned it into a clinical investigation subject to agency requirements, which include making sure that each subject or that person’s legally authorized representative gave consent.
“The IRB did not ‘make a connection’ that FDA regulations applied,” said the warning letter, which mentioned that an FDA inspector uncovered the “objectionable conditions” during a routine inspection in November 2011.
The study enrolled 122 patients and ended in December 2010, according to the National Institutes of Health.
The FDA letter ordered the health system’s review board to notify the agency in writing of the actions it planned to take to prevent similar violations in the future.
The warning letter said failure to explain the violations “adequately and promptly may result in regulatory action without further notice.”
A spokeswoman for Advocate Health Care did not make an official available for questions, saying today that the health system is still working on its response to the FDA.
“We take this matter very seriously,” Advocate said in a statement. “Our goal is to make sure that all of our Institutional Review Board activities, protocols and procedures related to clinical studies are in full compliance with FDA regulations. We have taken immediate steps to ensure this does not occur again and we are fully confident the matter will be resolved with the FDA shortly.”
The FDA letter notes that Advocate Health Care had previously submitted a corrective action plan but said the plan was unacceptable.
Among the problems was that Advocate’s IRB did not review a letter that the clinical investigator mailed to subjects after the study was completed.
“In addition, we find the clinical investigator’s letter to the subjects to be deficient because, among other things, it did not (1) inform the subject unambiguously that he/she was enrolled in a research study, or (2) include details of the study and other information that should have been contained in the informed consent document, including information about risk to the subject,” the FDA letter said.
Dr. Michael Carome, a former associate director for regulatory affairs in the U.S. Department of Health and Human Services’ Office for Human Research Protections, said the decision to go ahead with the study without obtaining patient consent was mind-boggling.
“It is a fundamental failure of the IRB,” said Carome, now with Public Citizen’s Health Research Group, “and it is really astonishing in 2012, when you consider that human subject protections have been at the forefront of research for the last three to four decades.”