Table 1.

Recommendations for primary outcomes for trials examining hemostatic blood products and agents

Clinical Condition	Primary Outcome Recommendations
Traumatic Injury (excluding isolated traumatic brain injury and burn injury)	For patients with traumatic injury, a 3 to 6-hour all-cause mortality is recommended as a primary outcome for hemostatic interventions, with robust evaluation of late safety-related outcomes In children with life-threatening traumatic hemorrhage, a primary outcome of death at either 6 or 24 hours is recommended.
Intracranial Hemorrhage	For patients with spontaneous or traumatic intracranial hemorrhage the recommended optimal primary outcome is a global patient-centered clinical outcome scale measured between 30–180 days after the event. For studies that may lack sufficient power for this, a combined clinical and radiographic endpoint (such as poor outcome associated with ICH expansion) is an acceptable second choice.
Cardiac Surgery/Mechanical Circulatory Support	For patients with bleeding secondary to cardiothoracic surgery, a primary efficacy endpoint of total allogeneic blood products (units vs ml/kg) administered intraoperatively and postoperatively to day 5 or hospital discharge is recommended. For clinical trials of patients on ECMO, the recommended primary outcome is a 5-point ordinal score of both thrombosis and bleeding severity adapted from the consensus definitions in Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For VAD studies, the recommended primary endpoint is freedom from disabling stroke (CTCAE ≥ Gr3 through 180 days.
Gastrointestinal Hemorrhage	For patients with acute gastrointestinal bleeding, the recommended primary outcome is a composite measure consisting of further bleeding (including persistent bleeding and rebleeding with primary assessment in 7 days),42 and cause-specific or bleed-related mortality at 30–42 days.
Inherited Bleeding Disorders	For the treatment of acute bleeding or for the prevention of surgical bleeding the recommended primary outcome is a composite scoring system incorporating the number of infusions required, rating on a clinical scale, and need for re-intervention For the prevention of bleeding events the recommended primary outcome is an annualized bleeding rate, quantifying the number of bleeding events over a period of time. For the long term and overall impact of bleeding, which is the ultimate goal in patients with inherited bleeding disorders, the recommended primary outcome is a composite of joint function (measured via an objective clinical scale or a patient reported functional score),50 chronic pain (measured via a validated scale), and HRQoL (both generic and specific)46 as proposed in a core outcome set for hemophilia gene therapy trials.
Hypoproliferative Thrombocytopenia	For patients with bleeding secondary to hypoproliferative thrombocytopenia, the recommended primary outcome for trials that examine the efficacy of blood products or hemostatic agents is the WHO Bleeding Assessment Score. Specifically, we recommend a WHO Grade of 2 or greater as a primary outcome in clinical trials of platelet threshold and efficacy.