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Novel Trial Design in Sepsis

  • Christopher W. Seymour
  • Derek C. Angus
Chapter

Abstract

  • Large, randomized clinical trials in sepsis have found few successful therapeutics in the past decade.

  • Traditional randomized trials of novel therapies, both in sepsis and in other fields, typically test a single drug or intervention in a single, and often narrowly defined, patient population, randomizing patients evenly to intervention versus control.

  • Newer designs in other fields have incorporated features to improve efficiency, such as the testing of multiple agents with a common control arm, the testing of a single agent within different patient subgroups, or the testing of agents within patients with different diseases but common mechanisms of action. Other features include randomization schemes that adapt over time, typically using Bayesian inference rules, to preferentially assign better performing agents within different subgroups.

  • These designs may be ideal to test new precision interventions in sepsis phenotypes, although rapid patient phenotyping will be required to enable more sophisticated randomization schemes.

  • Electronic health records found in many large healthcare systems are well-positioned to help deploy adaptive trials with point-of-care efficiency.

Keywords

Disease heterogeneity Phenotype Response-adaptive randomization Enrichment Adaptive trial Platform trial Basket trial Umbrella trial Embedded 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Critical Care Medicine, The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) CenterUniversity of Pittsburgh School of MedicinePittsburghUSA

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