FDA Warns PI for Eligibility Criteria, Study Drug Administration Issues
Failures to adhere to trial eligibility criteria and protocol requirements for investigational drug administration have netted a Pennsylvania-based investigator an FDA warning letter.
The warning letter, issued to rheumatologist Angela Stupi and posted online on Aug. 22, outlines a number of problems observed during the agency’s September 2022 inspection of her Cranberry Township, Penn., site, Advanced Rheumatology and Arthritis Wellness Center, where two trial protocols were assessed.
The three violations laid out in the warning letter fall under “a failure to ensure that the investigation was conducted according to the investigational plan.” The first relates to adherence to inclusion criteria.
Specifically, a participant was enrolled in the trial without having a stimulated whole salivary flow rate greater than 0.1 mL/min as required by the protocol’s eligibility criteria. Despite having no salivary flow rate measured at screening or baseline, the participant was randomized and given multiple doses of the investigational drug over six study visits, the letter says.
In Stupi’s written response, she explains that the sponsor removed the inclusion criterion through a protocol amendment and asked her to make a note to file (NTF) stating the screening lab results, physical exam and detailed conversation with the patient resulted in a score that met inclusion criteria.
Despite her claims, the FDA’s investigation revealed that the sponsor had not in fact nixed the eligibility criterion. “In fact, all versions of the protocol required a stimulated whole salivary flow rate >0.1 mL/min,” the agency said.
Another failure occurred when two patients were enrolled and randomized into a trial without having diagnoses of a moderate-to-severe condition with prior documented radiologic evidence.
“While we acknowledge your clinical assessment that [the patients] appeared to have met the clinical criteria for [the condition], your response is inadequate because you did not obtain or subsequently provide radiologic evidence (X-ray or radiologist’s report) to show that these subjects met the radiological criterion,” the FDA said. “Your failure to exclude subjects who did not have radiologic evidence of [the condition], as required by the protocol, raises concerns about the integrity of the data collected at your study site, and jeopardizes the rights, safety, and welfare of subjects.”
The final issue listed in the warning letter pertains to failures to properly administer the investigational drug as dictated by the protocol. Specifically, although the investigational drug was supposed to be injected in the thighs, upper arms or abdomens, two participants received injections to their forearms during multiple study visits.
The FDA judged Stupi’s response to the inspection observations inadequate because it did not provide sufficient information on planned corrective and preventive actions. The agency asked Stupi to provide additional information within 15 business days.
Read the warning letter here: https://tinyurl.com/yuen64n9.