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Population enrichment for critical care trials: phenotypes and differential outcomes

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Population enrichment for critical care trials : phenotypes and differential outcomes. / Shankar-Hari, Manu; Rubenfeld, Gordon D.

In: CURRENT OPINION IN CRITICAL CARE, Vol. 25, No. 5, 01.10.2019, p. 489-497.

Research output: Contribution to journalReview article

Harvard

Shankar-Hari, M & Rubenfeld, GD 2019, 'Population enrichment for critical care trials: phenotypes and differential outcomes', CURRENT OPINION IN CRITICAL CARE, vol. 25, no. 5, pp. 489-497. https://doi.org/10.1097/MCC.0000000000000641

APA

Shankar-Hari, M., & Rubenfeld, G. D. (2019). Population enrichment for critical care trials: phenotypes and differential outcomes. CURRENT OPINION IN CRITICAL CARE, 25(5), 489-497. https://doi.org/10.1097/MCC.0000000000000641

Vancouver

Shankar-Hari M, Rubenfeld GD. Population enrichment for critical care trials: phenotypes and differential outcomes. CURRENT OPINION IN CRITICAL CARE. 2019 Oct 1;25(5):489-497. https://doi.org/10.1097/MCC.0000000000000641

Author

Shankar-Hari, Manu ; Rubenfeld, Gordon D. / Population enrichment for critical care trials : phenotypes and differential outcomes. In: CURRENT OPINION IN CRITICAL CARE. 2019 ; Vol. 25, No. 5. pp. 489-497.

Bibtex Download

@article{bbf14abef4f34314a8b54783c5cbfbf6,
title = "Population enrichment for critical care trials: phenotypes and differential outcomes",
abstract = "PURPOSE OF REVIEW: Sepsis and acute respiratory distress syndrome (ARDS) are two heterogenous acute illnesses where numerous RCTs have indeterminate results. We present a narrative review on the recent developments in enriching patient populations for future sepsis and ARDS trials.RECENT FINDINGS: Many researchers are actively pursuing enrichment strategies to reduce heterogeneity to increase the sensitivity of future trials. Enrichment refers to the use of measurable patient characteristics, known before randomisation, to refine trial populations. Biomarkers could increase the diagnostic certainty of sepsis, whereas chest radiology training to enhance reliability of interpretation and stabilisation period of mechanical ventilation have been considered to increase the diagnostic certainty of ARDS. Clinical and biomarker data analyses identifies four to six sepsis clinical phenotypes and two ARDS clinical phenotypes. Similarly, leukocyte gene expression data identifies two to four sepsis molecular phenotypes. Use of a test-dose identifies ARDS subpopulations who are likely to benefit from higher PEEP. Early-phase trials report how a biomarker that is altered by the intervention, such as lymphocyte count for recombinant interleukin-7 therapy and higher check point inhibitor expression for anti-check point treatments in sepsis, could identify a higher treatment effect population for future trials.SUMMARY: Enrichment reduces heterogeneity and will enhance the sensitivity of future trials. However, enrichment, even when it identifies more homogenous populations, may not be efficient to deploy in trials or clinical practice.",
keywords = "acute respiratory distress syndrome, enrichment, sepsis, trial design",
author = "Manu Shankar-Hari and Rubenfeld, {Gordon D}",
year = "2019",
month = "10",
day = "1",
doi = "10.1097/MCC.0000000000000641",
language = "English",
volume = "25",
pages = "489--497",
journal = "CURRENT OPINION IN CRITICAL CARE",
issn = "1070-5295",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Population enrichment for critical care trials

T2 - phenotypes and differential outcomes

AU - Shankar-Hari, Manu

AU - Rubenfeld, Gordon D

PY - 2019/10/1

Y1 - 2019/10/1

N2 - PURPOSE OF REVIEW: Sepsis and acute respiratory distress syndrome (ARDS) are two heterogenous acute illnesses where numerous RCTs have indeterminate results. We present a narrative review on the recent developments in enriching patient populations for future sepsis and ARDS trials.RECENT FINDINGS: Many researchers are actively pursuing enrichment strategies to reduce heterogeneity to increase the sensitivity of future trials. Enrichment refers to the use of measurable patient characteristics, known before randomisation, to refine trial populations. Biomarkers could increase the diagnostic certainty of sepsis, whereas chest radiology training to enhance reliability of interpretation and stabilisation period of mechanical ventilation have been considered to increase the diagnostic certainty of ARDS. Clinical and biomarker data analyses identifies four to six sepsis clinical phenotypes and two ARDS clinical phenotypes. Similarly, leukocyte gene expression data identifies two to four sepsis molecular phenotypes. Use of a test-dose identifies ARDS subpopulations who are likely to benefit from higher PEEP. Early-phase trials report how a biomarker that is altered by the intervention, such as lymphocyte count for recombinant interleukin-7 therapy and higher check point inhibitor expression for anti-check point treatments in sepsis, could identify a higher treatment effect population for future trials.SUMMARY: Enrichment reduces heterogeneity and will enhance the sensitivity of future trials. However, enrichment, even when it identifies more homogenous populations, may not be efficient to deploy in trials or clinical practice.

AB - PURPOSE OF REVIEW: Sepsis and acute respiratory distress syndrome (ARDS) are two heterogenous acute illnesses where numerous RCTs have indeterminate results. We present a narrative review on the recent developments in enriching patient populations for future sepsis and ARDS trials.RECENT FINDINGS: Many researchers are actively pursuing enrichment strategies to reduce heterogeneity to increase the sensitivity of future trials. Enrichment refers to the use of measurable patient characteristics, known before randomisation, to refine trial populations. Biomarkers could increase the diagnostic certainty of sepsis, whereas chest radiology training to enhance reliability of interpretation and stabilisation period of mechanical ventilation have been considered to increase the diagnostic certainty of ARDS. Clinical and biomarker data analyses identifies four to six sepsis clinical phenotypes and two ARDS clinical phenotypes. Similarly, leukocyte gene expression data identifies two to four sepsis molecular phenotypes. Use of a test-dose identifies ARDS subpopulations who are likely to benefit from higher PEEP. Early-phase trials report how a biomarker that is altered by the intervention, such as lymphocyte count for recombinant interleukin-7 therapy and higher check point inhibitor expression for anti-check point treatments in sepsis, could identify a higher treatment effect population for future trials.SUMMARY: Enrichment reduces heterogeneity and will enhance the sensitivity of future trials. However, enrichment, even when it identifies more homogenous populations, may not be efficient to deploy in trials or clinical practice.

KW - acute respiratory distress syndrome

KW - enrichment

KW - sepsis

KW - trial design

UR - http://www.scopus.com/inward/record.url?scp=85071605666&partnerID=8YFLogxK

U2 - 10.1097/MCC.0000000000000641

DO - 10.1097/MCC.0000000000000641

M3 - Review article

C2 - 31335383

VL - 25

SP - 489

EP - 497

JO - CURRENT OPINION IN CRITICAL CARE

JF - CURRENT OPINION IN CRITICAL CARE

SN - 1070-5295

IS - 5

ER -

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