FDA drafts safety reporting guidance for drug and device investigators

Regulatory NewsRegulatory News | 01 October 2021 |  By 

The U.S. Food and Drug Administration has released draft guidance for clinical trial investigators outlining their safety reporting duties for investigational drugs and devices.
The draft, published on 29 September 2021, is focused exclusively on the role of investigators – not sponsors – and merges past final guidance from 2009 and 2012 on safety reporting that was previously mixed in with advice to sponsors. The prior guidance will remain in effect until the new document is finalized. FDA published separate draft guidance for sponsors earlier this year (RELATED: FDA releases new draft guidance on sponsor role for safety reporting requirements, Regulatory Focus 25 June 2021).
“Most of the information about the safety of a drug prior to marketing comes from clinical trials,” FDA wrote in the draft guidance. “Adverse event reports from investigators are therefore critically important, given that it is the investigators who observe subjects’ responses to an investigational drug.”
The draft guidance offers advice for clinical investigators on how to identify safety information that raises an “unanticipated problem involving risk to human subjects or others” for investigational drugs or “unanticipated adverse device effects” and how that information should be reported. It applies to investigational new drug application (IND) studies and investigational device exemption (IDE) studies.
IND studies
Clinical investigators must report serious adverse events (SAEs) to the trial sponsor immediately – as soon as possible after recognizing the SAE but generally no longer than one calendar day – regardless of whether they believe the event is related to the drug and even if the SAE is listed in the safety surveillance plan or the investigator brochure as an anticipated event.
The exception to this reporting requirement is if the SAE involves study endpoints, such as myocardial infarction in a trial evaluating a cardiovascular drug. In those cases, the SEA would be reported as outlined in the study protocol unless there was evidence that suggested the drug had caused the event, such as death from anaphylaxis after exposure to the drug.
The reported information should include a specified subject, a suspected drug, the reporting source if it is not the investigator, and a clinical description of the event. The clinical description should provide an assessment of whether there is a “reasonable possibility” that the drug caused the adverse event. It is the sponsor’s responsibility to determine whether an event is unexpected, the FDA explained.
“FDA interprets reasonable possibility to mean there is evidence to suggest a causal relationship between the drug and the adverse event,” the FDA noted in its guidance to investigators. “Factors that should be considered when making a causality assessment include, but are not limited to, temporal relationship of the event to drug administration; biologic plausibility, based on the mechanism of action of the drug or similar drugs in the same class; nonclinical evidence; and dechallenge-rechallenge information.”
Investigators are expected to report non-serious AEs as specified in the study protocol.
Under the draft guidance, investigators are required to report events to the IRB if the adverse event is a serious or an unexpected problem. The guidance outlines that investigators must review all IND safety reports and reports of safety information from IND-exempt bioavailability/bioequivalence studies received. Investigators must submit this information directly to the IRB unless they have confirmation that the sponsor has sent the information to the IRB. Some additional events that should be reported to the IRB by investigators include medication error reports, breach of privacy or confidentiality, and untimely destruction of study records, since they involve unanticipated problems related to study procedures.
IDE studies
For IDE studies, investigators must report unanticipated adverse device effects (UADEs) to both the trial sponsors and the IRBs as soon as possible but no later than 10 work days after the investigator discovers the effect.
“What qualifies as a UADE is expected to vary depending on the specific device and the way the device is used within the study,” the FDA wrote in the investigator guidance. “Therefore, sponsors are required to include risk information in the investigational plan, which may help investigators identify and assess potential UADEs.”
Investigators are also responsible for providing progress reports on anticipated and unanticipated adverse device effects at regular intervals, but at least annually, to sponsors, monitors, and IRBs, according to the draft guidance.
The agency is accepting public comments on the investigator guidance until 29 November 2021.

Investigator Responsibilities — Safety Reporting for Investigational Drugs and Devices: Guidance for Industry


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