The prominent consumer watchdog group Public Citizen is calling for federal regulators to immediately investigate a clinical trial involving epileptics, which it says put patients with life-threatening seizures at an unreasonable risk.
In a Health Letter published this month, Public Citizen called for an ethics review of a trial funded by the National Institute of Health (NIH), which the group says exposed patients to unacceptable and avoidable risks, with a disproportionate number of the participants being minorities.
Public Citizen indicates it sent a letter (PDF) to the U.S. Department of Health and Human Services’ Office for Human Research Protection (OHRP) and the U.S. Food and Drug Administration (FDA) requesting the investigation back in June.
The study, known as the Established Status Epilepticus Treatment Trial (ESETT) involved 462 adults and children suffering from epilepsy seizures lasting longer than five minutes, known as episodes of status epilepticus, seen by researchers in emergency departments in 58 hospitals across the United States. These patients’ seizures had not resolved after a standard initial treatment of a benzodiazepine, such as diazepam.
The researchers randomly assigned the subjects to receive one of three FDA-approved seizure medications, including Depakote (valproate), Keppra XR (levetiracetam), or Cerebyx (fosphenytoin).
Public Citizen claims the trials exposed some patients to risks that violate ethical and regulator human research standards. The group indicates these patients were never given informed consent of the subjects, or in the case of children, their parents.
“Public Citizen’s analysis of ESETT, which enrolled subjects from November 2015 to December 2018, identified major flaws in the design of the study that resulted in all three trial groups potentially exposing some subjects to care that was significantly different from the usual care for status epilepticus patients,” the health letter states. “These deviations from usual care predictably could have delayed resolution of some subjects’ status epilepticus that had not responded to a benzodiazepine, increasing the risk of adverse neurological outcomes and death.”
The group claims the trial was blinded, meaning doctors did not know which of the three drugs were given to the subjects. Public Citizen points out that, typically, treatment for such prolonged seizures is based on their long-term seizure drug use, age, compliance and other underlying conditions. But due to the randomization of the trial, these factors were not weighed into which drugs the human test subjects were given.
The letter also notes the test trial enrolled a “disproportionately high number of Black subjects”, with Black patients accounting for 42% of all subjects. Only about 27% of patients hospitalized for status epilepticus are black, according to Public Citizen.
Public Citizen sent another letter (PDF) to NIH Director Francis Collins, noting this is not an unusual event, and that a number of clinical trials funded by NIH over the last two decades failed to incorporate usual-care clinical practices into their design.
While both the FDA and the OHRP have acknowledged Public Citizen’s request for an investigation, neither have confirmed whether formal investigations have begun or will be launched, according to the letter.