Abigail Baim-Lance1,2, Katelyn B Ferreira3, Harvey Jay Cohen4, Susan S Ellenberg5, George A Kuchel6, Christine Ritchie7, Greg A Sachs8,9, Dalane Kitzman10, R Sean Morrison3,11, Albert Siu3,11. 1. Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1070, New York, NY, 10029, USA. Abigail.baim-lance@mssm.edu. 2. Geriatric Research Education and Clinical Center (GRECC), James J Peters VA Medical Center, Bronx, NY, USA. Abigail.baim-lance@mssm.edu. 3. Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1070, New York, NY, 10029, USA. 4. Center for the Study of Aging and Human Development, Duke University School of Medicine, Durham, NC, USA. 5. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 6. UConn Center on Aging, University of Connecticut, Farmington, CT, USA. 7. Division of Palliative Care and Geriatric Medicine and the Mongan Institute Center for Aging and Serious Illness, Massachusetts General Hospital, Boston, MA, USA. 8. Indiana University Center for Aging Research, Regenstrief Institute, Indianapolis, IN, USA. 9. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. 10. Department of Internal Medicine: Sections on Cardiovascular Medicine and Geriatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA. 11. Geriatric Research Education and Clinical Center (GRECC), James J Peters VA Medical Center, Bronx, NY, USA.
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.
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.
Authors: Zubin J Eapen; John P Vavalle; Christopher B Granger; Robert A Harrington; Eric D Peterson; Robert M Califf Journal: Am Heart J Date: 2013-03-13 Impact factor: 4.749
Authors: Amy S Kelley; Kenneth E Covinsky; Rebecca J Gorges; Karen McKendrick; Evan Bollens-Lund; R Sean Morrison; Christine S Ritchie Journal: Health Serv Res Date: 2016-03-18 Impact factor: 3.402
Authors: C A Naranjo; U Busto; E M Sellers; P Sandor; I Ruiz; E A Roberts; E Janecek; C Domecq; D J Greenblatt Journal: Clin Pharmacol Ther Date: 1981-08 Impact factor: 6.875
Authors: Irene J Higginson; Barbara Gomes; Natalia Calanzani; Wei Gao; Claudia Bausewein; Barbara A Daveson; Luc Deliens; Pedro L Ferreira; Franco Toscani; Marjolein Gysels; Lucas Ceulemans; Steffen T Simon; Joachim Cohen; Richard Harding Journal: Palliat Med Date: 2013-05-23 Impact factor: 4.762