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. 2021 Mar 1;273(3):395-401.
doi: 10.1097/SLA.0000000000004563.

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials

John B Holcomb  1 , Ernest E Moore  2 , Jason L Sperry  3 , Jan O Jansen  4 , Martin A Schreiber  5 , Deborah J Del Junco  6 , Philip C Spinella  7 , Angela Sauaia  8 , Karim Brohi  9 , Eileen M Bulger  10 , Andrew P Cap  11 , John R Hess  12 , Donald Jenkins  13 , Roger J Lewis  14 , Matthew D Neal  3 , Craig Newgard  15 , Shibani Pati  16 , Anthony E Pusateri  17 , Sandro Rizoli  18 , Robert T Russell  19 , Stacy A Shackelford  20 , Deborah M Stein  21 , Marie E Steiner  22 , Henry Wang  23 , Kevin R Ward  24 , Pampee Young  25
Affiliations

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials

John B Holcomb et al. Ann Surg. .

Abstract

Objective: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia.

Background: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators.

Methods: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability.

Conclusions: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

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Conflict of interest statement

Deborah J. del Junco received no funding support or conflicts of interest to disclose and Hemanext. Brohi K reports no active or recent relevant conflicts of interests. Funding support from Barts Health NHS Trust, Barts Charity, National Institute of Health Research UK, Medical Research Council UK. Andrew P. Cap is an active duty officer in the US Army and has no conflicts of interest to disclose. Newgard C has no conflicts of interest to report. Funding for trauma research from NICHD and HRSA. Anthony E. Pusateri is a US Government employee and has no conflicts of interest.

Comment in

References

    1. National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources Hemostasis Clinical Trial Outcomes Working Group. Sept 23-24 2019. Bethesda, MD. Available at: https://www.evensi.us/hemostasis-clinical-trials-working-groupnih-last accessed 2 July 2020.
    1. Spinella PC, Kassar NE, Cap AP, et al. and the Hemostasis Trials Outcomes Working Group. Recommended primary outcomes for clinical trials evaluating hemostatic blood products and agents in patients with bleeding. Under review, Transfusion 2020.
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