Federal Regulators’ Failure to Act Endangered CLOVERS Trial Patients After Alarming Design Flaws, Ethical Lapses Were Identified

Public Citizen Complaint to OHRP Prompted ‘Extensive Revisions’ to Trial Design and Consent Form, But More Action by Agency is Needed

WASHINGTON, D.C. – The Office for Human Research Protections (OHRP) put hundreds of seriously ill sepsis patients at risk by not suspending enrollment in a flawed clinical trial, Public Citizen said today in a letter to the agency. The Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial continued even as much needed changes were being made to the study’s design and consent form to address alarming ethical and regulatory lapses.

The goal of the CLOVERS trial – which is funded by the National Institutes of Health (NIH) – as originally designed was to determine which of two extreme, highly unusual, treatment strategies for sepsis results in more patient deaths. In a 2018 complaint to OHRP, Public Citizen noted the trial did not comply with federal regulations or basic ethical principles for protecting human research subjects. The trial’s original design exposed patients to unacceptable risks, and its original consent form failed to adequately disclose the nature and risks of the research.

“OHRP knowingly allowed subjects to be enrolled in a trial that exposed them to unacceptable risk without the subjects understanding the true nature and risks of the experiment,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “Such failure represents a stunning abdication of the agency’s duty to protect the rights, welfare, and wellbeing of human subjects.”

In a response to Public Citizen’s 2018 letter, OHRP engaged in an extensive dialogue with NIH officials and the CLOVERS trial researchers, which according to a Sept. 28 OHRP letter to Public Citizen resulted in “extensive revisions” being made to the trial’s design and consent form, including better informing patients of the risks involved in the study. However, the agency’s refusal to order a suspension of the trial until the problems were addressed and changes finalized is inexcusable, Public Citizen said in its letter.

Public Citizen is urging the agency to require the CLOVERS trial researchers to officially inform surviving patients (or next of kin of deceased patients) who were enrolled in the study before changes were made to the trial’s design and consent form of the previously undisclosed risks the trial posed.