Developing and Disseminating the Approach to Defining, Classifying, and Monitoring Adverse and Serious Adverse Events in Clinical Trials involving Older, Seriously Ill Populations
Funded Grant
Overview
Affiliation
View All
Overview
description
PROJECT SUMMARY Research to support older adults with serious illness is a public health priority. Defining and monitoring serious and other adverse events [(S)AEs] in clinical trials involving older adults with serious illness pose challenges to investigators, regulators, sponsor agency members, and patient stakeholders. Challenges include the reporting of events that are: implausibly related to the intervention, misaligned with patient values, and/or caused by already established, well- known relationships. There are also challenges with data and safety monitoring board education, oversight and communication. In 2020, the NIA sponsored an initiative to convene a multi-disciplinary group that met four times over 12 months. Efforts of the convening resulted in new framework anchored by six principles including: 1) Consider interventions, populations and settings (e.g., whether the study is FDA-regulated and therefore must adhere to specific reporting standards, or alternatively, whether there is investigator discretion as in socio- behavioral trials); 2) Adhere to the importance of safety reporting but use aggregate and routine over singular and expedited reporting for most (S)AEs; 3) Prioritize intervention relatedness (i.e., whether the (S)AE is ‘unlikely,’ ‘possibly,’ or ‘probably’ related to the intervention mechanism using existing tools to support unbiased causality identification); 4) Subsume expectedness into relatedness determination; given difficulties in forecasting the full range of (S)AEs in seriously ill older adults at a trial’s outset, expectedness should be ascertained when events occur by “ruling out underlying disease states”; 5) Consider concordance with patients’ goals of care; and 6) Assess seriousness, marking the events regulatory bodies are most concerned about (e.g., death, hospitalization, life threatening events), after relatedness and goal-concordance to highlight (S)AEs of greatest concern, and report them in an expedited, case-by-case manner. The current proposed project will reconvene a working group to initially develop the details of the methodology for defining, classifying and reporting (S)AEs for clinical trials involving older, seriously ill adults. The group will focus on better defining and tracking interventions, populations, settings; elaborating upon the relatedness determination; further developing how to meaningfully determine patient goal concordance with events; and develop content to align these efforts with existing NIA and related tools and guidance. This effort will involve the creation of publicly available tools to support the research community, and the widespread dissemination of the framework to encourage its implementation within clinical trials.
