UCLA’s guidance for UPs provides best practice model

Clear definitions, easy links

The University of California Los Angeles (UCLA) recently updated its guidance on reporting unanticipated problems (UPs), adverse events (AEs), and other incidents in human subject research, providing a model for IRBs.

The 11-page guidance provides thorough definitions, examples, policy descriptions, and a diagram to provide investigators, IRB staff, and IRB members with clear instructions for filing reports. Titled “Guidance and Procedure: Post-Approval Reporting Requirements (PAR) for Investigators: Reporting of Unanticipated Problems, Including Adverse Events as well as Protocol Violations, Deviations and Incidents and the Reporting of Updated Study Safety Information,” the guidance includes 19 links to regulatory and other information.

The UCLA policy offers this summary of the Office for Human Research Protection’s (OHRP’s) definition of unanticipated problems: “An event or outcome that meets the following criteria: 1) unexpected; 2) related or possibly related to participation in the research; and 3) places subjects or others at a greater risk of harm than was previously known or recognized.”

The UCLA guidance for UPs features these main categories:

• general overview;

• definitions;

• policy;

• PI reporting responsibilities: adverse events, protocol violations, deviations, and incidents, and updated study safety information;

• IRB responsibilities and procedures;

• IRB reporting requirements;

• references and regulations.

For example, under AE reporting, the guidance asks investigators to report, within 10 working days, any internal or external adverse event that meets the criteria for an unanticipated problem; or that was expected and related but had a higher frequency of occurrence or higher level of severity; or that indicated a potential risk that requires notification of previously enrolled subjects; or that requires prompt reporting according to the protocol or study sponsor.

UCLA investigators also must report within three working days any internal subject deaths that occurred in the interventional study, were unexpected, and were related or possibly related to the research participation.

Under IRB Responsibilities and Procedures, the guidance outlines how the IRB is responsible for reviewing written reports of events and determining if they meet the criteria of an unanticipated problem involving risk to subjects and others. Reports of problems that could be UPs will be considered by the IRB, which could decide that a problem is a UP or that it requires no further action. Other possible actions by the IRB would include these:

• accepting an investigator’s corrective action plan;

• modification of the research protocol, continuing review schedule, recruitment or informed consent;

• notifying current or previously enrolled subjects of the new information;

• observing the consent process through use of a consent monitor;

• requiring frequent status reports to the IRB;

• educational intervention for investigators and staff;

• referral to an on-site review;

• suspension of all or parts of the research;

• termination of the research.