33 - A Novel Approach to Adverse Event Reporting in Behavioral and Health Services Trials Involving Seriously Ill and Older Adults

Background: : Clinical trials involving seriously ill and/or older adults are critical to advancing the science of geriatrics and palliative care. However, current serious/adverse event [(S)AE] reporting guidance lacks the nuance to reflect the expected increased morbidity and mortality seen in these study populations, resulting in burdensome expedited reporting.

Program

Description: : An expert 38-member panel comprised of representatives from federal agencies, clinical research scientists in geriatrics and palliative care, national clinical and scientific organizations, and medical ethics scholars, convened to: (1) develop a decision algorithm that was aligned with existing requirements (e.g. the Common Rule and required reporting of unanticipated problems to the Office for Human Research Protections); (2) refine the approach for usability, and (3) develop dissemination strategies. The lead team and expert panel developed the approach which included key novel elements to account for increased morbidity and mortality in seriously ill and older study populations: (1) accounting for study types (e.g. behavioral interventions); (2) prioritizing event relatedness over other considerations (e.g. seriousness); and (3) the alignment of events with documented goals of care (e.g. progression of disease and withdrawal of unwanted life-sustaining treatments resulting in death).

Program

Assessment: : During a second phase of the project, the approach was refined into a reporting toolkit to promote usability. The (S)AE decision tree was expanded into an algorithm comprised of questions pertinent to assessing each node of the tree (e.g., how to determine whether an (S)AE is “at least possibly related” to clinical trial procedures, or whether an (S)AE occurred under “goal aligned” conditions). A set of cases demonstrates reporting guidance across diverse clinical trials to show real world applications. The panel also developed a “frequently asked questions” list and glossary of key terms. Plans are underway regarding the placement of the toolkit with national and federal organizations, with a focus on broad dissemination. The algorithm and sample cases will be included as part of this presentation.

Limitations:: Careful attention was paid to triangulate existing regulation as the “floor” to ensure usability of the algorithm. It also became apparent that it was critical to “stress test” the algorithm with diverse (non-drug/non-device) case studies with the expert panel. Importantly, the approach does not account for local institutional and other requirements by funders and investigators will need to be cognizant of as they develop data safety and monitoring plans.

Discussion: : Clinical trials involving older adults and those with serious illness will benefit from an approach to (S)AE reporting that accounts for patients’ care preferences, the type of study, and prioritization of intervention relatedness. The algorithm and supporting materials will offer practical tools for researchers and study monitors to facilitate appropriate (S)AE reporting, comply with federal guidance, and facilitate research that is inclusive of seriously ill and older adults. Future toolkit dissemination will embed the approach into clinical research practice. Next steps include engagement with additional key national organizations to disseminate and implement this novel approach.