Recurrent event frailty models reduced time-varying and other biases in evaluating transfusion protocols for traumatic hemorrhage

Sangbum Choi, Mohammad H. Rahbar, Jing Ning, Deborah J. del Junco, Elaheh Rahbar, Chuan Hong, Jin Piao, Erin E. Fox, John B. Holcomb

Research output: Contribution to journalArticlepeer-review


Objective Transfusion research seeks to improve survival for severely injured and hemorrhaging patients using optimal plasma and platelet ratios over red blood cells (RBCs). However, most published studies comparing different ratios are plagued with serious bias and ignore time-varying effects. We applied joint recurrent event frailty models to increase validity and clinical utility. Study Design and Setting Using the PRospective Observational Multicenter Major Trauma Transfusion study data, our joint random-effects models estimated the association of (1) clinical covariates with transfusion rate intensities and (2) varying plasma:RBC and platelet:RBC ratios with survival over the 24 hours after hospital admission. Along with survival time, baseline patient vital signs, laboratory values, and longitudinal data on types and volumes of transfusions were included. Results Baseline systolic blood pressure, heart rate, pH, and hemoglobin were significantly associated with RBC transfusion rates. Increased transfusion rates (per hour) of plasma (P = 0.05), platelets (P < 0.001), or RBCs were associated with increased 24-hour mortality. Higher ratios of plasma:RBC (P = 0.107) and platelet:RBC (P < 0.001) were associated with reduced mortality in a time-varying pattern (P < 0.001). Conclusions The proposed joint analysis of transfusion rates and ratios offers a more valid statistical approach to evaluate survival effects in the presence of informative censoring by early death.

Original languageEnglish
Pages (from-to)52-59.e1
JournalJournal of Clinical Epidemiology
Publication statusPublished - 2016 Sept 1

Bibliographical note

Funding Information:
This research is funded by the National Heart, Lung, and Blood Institute, United States (NHLBI; R21 HL109479 ), awarded to The University of Texas Health Science Center at Houston (UTHealth). The authors also acknowledge the support provided by the Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS) for this project. CCTS is mainly funded by the United States NIH Centers for Translational Science Award (NIH CTSA) grant (UL1 RR024148), awarded to UTHealth in 2006 by the National Center for Research Resources (NCRR) and its renewal (UL1 TR000371) by the National Center for Advancing Translational Sciences (NCATS), United States. Appendix A

Publisher Copyright:
© 2016 Elsevier Inc.


  • Hemorrhage
  • Joint modeling
  • Multivariate recurrent events
  • Survival analysis
  • Transfusion ratio
  • Trauma

ASJC Scopus subject areas

  • Epidemiology


Dive into the research topics of 'Recurrent event frailty models reduced time-varying and other biases in evaluating transfusion protocols for traumatic hemorrhage'. Together they form a unique fingerprint.

Cite this