Unanticipated Problem/Event Reports and Investigator Non-Compliance

Unanticipated Problem

Submit promptly a Problem Event Report to the BSPH IRB through the PHIRST system in accordance with IRB Policy No. 103.06, “Reports of Unanticipated Problems Involving Risks to Participants or to Others” if, during the course of the study, a negative event or problem occurs that includes all three of these characteristics:

1. Problem or event harms or poses risk to participants or others
2. Is caused by, or related to, the study-related procedures or processes.
3. Is unanticipated, meaning that the risk was not included in the research plan or consent form, or that its severity or frequency is higher than expected at the beginning of the study

The IRB will review these reports at a convened meeting. Problems and Events include things such as losing a laptop with study identifiers on it or discovering that a supply of drug for a study is tainted or unavailable. It may include missed study procedures, such as pregnancy testing, without which a participant might be put at increased risk of harm. It includes enrolling someone who does not meet study eligibility criteria. Please see the Policy for more examples.

Investigator Non-Compliance

Investigators are responsible for reporting any incidents of protocol non-compliance in accordance with BSPH IRB Policy No. 103.07.

“Non-compliance” is defined as failure on the part of the PI, any member of the study team, or any individual involved in research review or oversight to:

* follow the terms of BSPH IRB approval (including the approved Research Plan and Consent Process), or

* abide by applicable laws or regulations or BSPH policies, including failure to submit research for IRB review and approval prior to commencing research.

“Minor non-compliance” is defined to be reported incidents or events which are not either serious or continuing non-compliance.

“Serious non-compliance” is defined to be failure to comply with laws or regulations, BSPH policies, or the requirements or determinations of the IRB, when that failure actually or potentially increases risk to participants or adversely affects the rights and welfare of the participants. A single instance of non-compliance may be determined by the IRB to be serious non-compliance (i.e., continuing non-compliance is not a necessary prerequisite of serious non-compliance). The BSPH IRB is obligated to report incidents of serious non-compliance to the sponsor and to federal authorities.

“Continuing non-compliance” is defined to be a pattern of behavior or minor non- compliance issues (even when none of them rise to serious non-compliance) that, if unaddressed, may compromise the integrity of human research protections applicable to ongoing or future studies. The BSPH IRB is obligated to report continuing non- compliance to the sponsor and to federal authorities.

Protocol Deviations:

The term “protocol deviation” is not defined by either the HHS human subjects regulations (45 CFR 46) or the FDA human subjects regulations (21 CFR 50). For BSPH purposes, a protocol deviation is a minor or administrative departure (see definitions below) from the protocol procedures approved by the IRB that was made by the PI without prior IRB approval. In this context, “minor or administrative” protocol deviations are defined as those that do not “affect the scientific soundness of the research plan or the rights, safety, or welfare of human subjects.” Examples of minor or administrative deviations could include: follow up visits that occurred outside the time frame specified in the protocol because of the participant’s schedule, or blood samples obtained at times close to but not precisely at the time points specified in the protocol.

A PI may report all protocol deviations (i.e., an event that meets this definition) with the Continuing Review/Progress Report using the Protocol Deviation Summary Form.