PI Warned for Failing to Stick to Treatment Phases, Maintain IRB Approval
A Detroit, Mich.-based principal investigator’s (PI) failure to renew IRB approval during a trial and adhere to the required treatment phases in a trial’s investigational plan has netted an FDA warning letter.
The letter, issued to Jeffrey Taub, a doctor specializing in hematology and oncology at the Children’s Hospital of Michigan, outlines two violations, one of which specifically involved a pediatric patient, as well as the agency’s requests for greater details on corrective actions.
The first, a failure to ensure that the trial was carried out according to the investigational plan, centers on a six-year-old participant who was mistakenly allowed to continue receiving the investigational treatment past the cutoff point, resulting in extra doses and additional five-day cycles. This mistake put the participant at a higher risk of serious toxicities that included neurotoxicity and hematologic toxicity, according to the agency.
Taub’s written response acknowledged the error, assigned blame to a sub-investigator who misunderstood the drug administration plan and said the IRB was alerted by its deadline. It also stated the participant would be monitored according to the protocol during each remaining study visit for any related adverse events or toxicities and noted four follow up actions taken at the site.
This response, however, lacked important details, the FDA said, including information on the policies and procedures the site would implement to ensure compliance. And because of the gravity of the issue, the agency requested documentation surrounding these policies and procedures, including randomization assignments.
The second violation, a failure to ensure continued IRB review and approval of trial conduct, centers on a trial’s IRB approval that lapsed from Jan. 14-24, 2022. Despite this, the study treatment was dispensed to a participant and bone marrow and peripheral blood specimen samples were gathered from a participant during this time period.
This issue, the PI said, stemmed from “a multitiered review of the continuing review, which delayed the continuing review from being addressed at a timely, regularly scheduled IRB meeting, as well as to staff turnover after submission of a continuing review.”
Additionally, he noted the study had been reapproved and study staff responsible for continuing reviews would begin receiving 30-, 60- and 90-day email reminders before study approval expirations in addition to receiving retraining. As part of this latter strategy, study staff would initiate the continuing review process at the 90-day mark to allow for submission prior to the 30-day reminder.
Again, the FDA did not find this response sufficient and sought more details.
“For example, you did not provide sufficient details about the policies and procedures you would institute at your site to ensure submission of IRB continuing review before study approval expiration dates, including procedures regarding email notifications at 90, 60 and 30 days before the date on which the study’s approval expires,” the agency said. “Without this information, we are unable to determine if your corrective action plan is adequate to prevent similar violations in the future.”
Read the full warning letter here.