Elicitation of prior probability distributions for a proposed Bayesian randomized clinical trial of whole blood for trauma resuscitation

Abstract

BACKGROUND Whole blood trauma resuscitation is conceptually appealing and increasingly used but lacks evidence. A randomized controlled trial is needed but challenging to design. A Bayesian approach might be more efficient and more interpretable than a conventional frequentist design. We report the results on an elicitation meeting to create prior probability distributions to help develop such a trial. METHODS In‐person expert elicitation meeting, based on Sheffield Elicitation Framework methodology. We used an interactive graphical tool to elicit the quantities of interest (24‐hour mortality and certainty required). Two rounds were conducted, with an intervening discussion of deidentified responses. Individual responses were aggregated into probability distributions. RESULTS Fifteen experts participated. The pooled belief was that the median 24‐hour mortality of trauma patients with hemorrhagic shock treated with component therapy (the current standard of care) was 19% (95% credible interval [CrI], 6%‐45%), and the median 24‐hour mortality of those treated with whole blood, 16% (95% CrI, 5%‐39%). The pooled prior distribution for the relative risk had a median of 0.84 (95% CrI, 0.26‐3.1), indicating that the expert group had a 64% prior belief that whole blood decreases 24‐hour mortality compared to component therapy. CONCLUSIONS Experts had moderately strong beliefs that whole blood reduces the 24‐hour mortality of trauma patients with hemorrhagic shock. These data will assist with the design and planning of a Bayesian trial of whole blood resuscitation, which will help to answer a key question in contemporary transfusion practice.

Prior Elicitation for Use in Clinical Trial Design and Analysis: A Literature Review

“…Generally, prior probability distributions for binary outcomes are elicited in terms of Beta priors [ 31 , 45 , 46 , 56 , 58 ]. Aupiais and colleagues, for example, proposed a non-inferiority approach, in a Bayesian framework, for sequential monitoring of rare dichotomous safety events, incorporating experts’ opinions to define the margin.…”

“…The SHELF elicitation procedure is a widely used approach to elicitate Beta event rate in a clinical trial [ 12 ] and is the most commonly used software for elicitation ( Table 1 ). Jansen et al [ 45 ], for example, elicited the prior distribution for the 24-h trauma mortality in patients with haemorrhagic complications combining beta distributions using the SHELF elicitation procedure. The single expert distributions were elicited using the roulette method than a linear poling of the distributions has been performed [ 45 ].…”

Civilian walking blood bank emergency preparedness plan

“…LTOWB transfusion is becoming more common, albeit without randomized studies documenting efficacy. 2,16,[24][25][26][27][28][29][30][31][32] However, supply chain issues may complicate timely infectious disease testing. Emergency use of the WBB would not allow for the time (typically requiring 12-24 h after donation) required for complete infectious disease testing.…”

“…Fully infectious‐disease‐tested ABO‐type specific whole blood and LTOWB are FDA‐licensed products and the AABB standards allow for the transfusion of ABO‐type specific WB and LTOWB. LTOWB transfusion is becoming more common, albeit without randomized studies documenting efficacy 2,16,24–32 . However, supply chain issues may complicate timely infectious disease testing.…”

Whole blood for trauma patients: Outcomes at higher doses

“…The obvious next step is randomized controlled trials that compare clinical outcomes in patients treated with WB compared with component therapy. To that end, there are several RCTs in development including the TROOP trial that are designed to address the limitations of the current literature 23 . Even in the absence of a defined mortality benefit, there are still likely advantages of LTOWB in its ability to be used effectively prehospital, or on other non‐mortality measures such as a reduced use of blood products during resuscitation.…”