Abstract
Background
Clinical trials are needed to study topics relevant to older adults with serious illness. Investigators conducting clinical trials with this population are challenged by how to appropriately define, classify, report, and monitor serious and non-serious adverse events (SAEs/AEs), given that some traditionally reported AEs (pressure ulcers, delirium) and SAEs (death, hospitalization) are common in persons with serious illness, and may be consistent with their goals of care.
Objectives
A multi-stakeholder group convened to establish greater clarity on and new approaches to address this critical issue.
Participants
Thirty-two study investigators, members of regulatory and sponsor agencies, and patient stakeholders took part.
Approach
The group met virtually four times and, using a collaborative approach, conducted a survey, select interviews, and reviewed regulatory guidance to collectively define the problem and identify a new approach.
Results
SAE/AE challenges fell into two areas: (1) definitions and classifications, including (a) implausible relationships, (b) misalignment with patient-centered care goals, and (c) well-known associations, and (2) reporting and monitoring, including (a) limited guidance, (b) inconsistent standards across regulators, and (c) Data Safety Monitoring Board (DSMB) member knowledge gaps. Problems largely reflected practice norms rather than regulatory requirements that already support context-specific and aggregate reporting. Approaches can be improved by adopting principles that better align strategies for addressing adverse events with the type of intervention being tested, favoring routine and aggregate over expedited reporting, and prioritizing how SAE/AEs relate to patient-centered care goals. Reporting plans and decisions should follow an algorithm underpinned by these principles.
Conclusions
Adoption of the proposed approach—and supporting it with education and better alignment with regulatory guidance and procedures—could improve the quality and efficiency of clinical trials’ safety involving older adults with serious illness and other vulnerable populations.
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Acknowledgements
We would like to acknowledge the full convening group for their significant collective contribution to the development of the ideas presented in this manuscript, and in particular Abby Archer who provided administrative support for the convening. Individuals participating in the convening contributed personal opinions and were not expressing the views of their respective agencies and institutions. The convening and resulting manuscript was supported by an administrative supplement from the National Institutes on Aging U24AG059624 (Coordinating Center of the Claude D. Pepper Older Americans Independence Centers; PI: Kitzman). Additional support was provided by National Institutes on Aging P30AG028741 (Enhancing Independence in Elders with Serious Illness; PIs: Siu, Morrison) and the National Palliative Care Research Center (NPCRC). Some of the ideas included in this manuscript were presented at the American Academy of Hospice and Palliative Medicine 2022 State of the Science on February 12, 2022.
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Baim-Lance, ., Ferreira, K.B., Cohen, H.J. et al. Improving the Approach to Defining, Classifying, Reporting and Monitoring Adverse Events in Seriously Ill Older Adults: Recommendations from a Multi-stakeholder Convening. J GEN INTERN MED (2022). https://doi.org/10.1007/s11606-022-07646-7
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DOI: https://doi.org/10.1007/s11606-022-07646-7