TY - JOUR
T1 - Addressing the Evidence Gap in Aneurysmal Subarachnoid Hemorrhage
T2 - The Need for a Pragmatic Randomized Trial Platform
AU - Kamel, Hooman
AU - Suarez, Jose I.
AU - Connolly, E. Sander
AU - Amin-Hanjani, Sepideh
AU - Mack, William T.
AU - Chou, Sherry Hsiang Yi
AU - Busl, Katharina M.
AU - Derdeyn, Colin P.
AU - Dangayach, Neha S.
AU - Elm, Jordan E.
AU - Beall, Jonathan
AU - Ko, Nerissa U.
N1 - Publisher Copyright:
© 2024 American Heart Association, Inc.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.
AB - Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.
KW - cerebral hemorrhage
KW - clinical trial
KW - ischemic stroke
KW - subarachnoid hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=85199710535&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.124.048089
DO - 10.1161/STROKEAHA.124.048089
M3 - Review article
C2 - 39051124
AN - SCOPUS:85199710535
SN - 0039-2499
VL - 55
SP - 2397
EP - 2400
JO - Stroke
JF - Stroke
IS - 9
ER -