Real-world causal evidence for planned predictive enrichment in critical care trials: A scoping review
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Real-world causal evidence for planned predictive enrichment in critical care trials : A scoping review. / Kaas-Hansen, Benjamin Skov; Granholm, Anders; Sivapalan, Praleene; Anthon, Carl Thomas; Schjørring, Olav Lilleholt; Maagaard, Mathias; Kjaer, Maj-Brit Nørregaard; Mølgaard, Jesper; Ellekjaer, Karen Louise; Fagerberg, Steen Kåre; Lange, Theis; Møller, Morten Hylander; Perner, Anders.
In: Acta Anaesthesiologica Scandinavica, Vol. 68, No. 1, 2023, p. 16-25.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Real-world causal evidence for planned predictive enrichment in critical care trials
T2 - A scoping review
AU - Kaas-Hansen, Benjamin Skov
AU - Granholm, Anders
AU - Sivapalan, Praleene
AU - Anthon, Carl Thomas
AU - Schjørring, Olav Lilleholt
AU - Maagaard, Mathias
AU - Kjaer, Maj-Brit Nørregaard
AU - Mølgaard, Jesper
AU - Ellekjaer, Karen Louise
AU - Fagerberg, Steen Kåre
AU - Lange, Theis
AU - Møller, Morten Hylander
AU - Perner, Anders
N1 - © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: Randomised clinical trials in critical care are prone to inconclusiveness due, in part, to undue optimism about effect sizes and suboptimal accounting for heterogeneous treatment effects. Although causal evidence from rich real-world critical care can help overcome these challenges by informing predictive enrichment, no overview exists.METHODS: We conducted a scoping review, systematically searching 10 general and speciality journals for reports published on or after 1 January 2018, of randomised clinical trials enrolling adult critically ill patients. We collected trial metadata on 22 variables including recruitment period, intervention type and early stopping (including reasons) as well as data on the use of causal evidence from secondary data for planned predictive enrichment.RESULTS: We screened 9020 records and included 316 unique RCTs with a total of 268,563 randomised participants. One hundred seventy-three (55%) trials tested drug interventions, 101 (32%) management strategies and 42 (13%) devices. The median duration of enrolment was 2.2 (IQR: 1.3-3.4) years, and 83% of trials randomised less than 1000 participants. Thirty-six trials (11%) were restricted to COVID-19 patients. Of the 55 (17%) trials that stopped early, 23 (42%) used predefined rules; futility, slow enrolment and safety concerns were the commonest stopping reasons. None of the included RCTs had used causal evidence from secondary data for planned predictive enrichment.CONCLUSION: Work is needed to harness the rich multiverse of critical care data and establish its utility in critical care RCTs. Such work will likely need to leverage methodology from interventional and analytical epidemiology as well as data science.
AB - BACKGROUND: Randomised clinical trials in critical care are prone to inconclusiveness due, in part, to undue optimism about effect sizes and suboptimal accounting for heterogeneous treatment effects. Although causal evidence from rich real-world critical care can help overcome these challenges by informing predictive enrichment, no overview exists.METHODS: We conducted a scoping review, systematically searching 10 general and speciality journals for reports published on or after 1 January 2018, of randomised clinical trials enrolling adult critically ill patients. We collected trial metadata on 22 variables including recruitment period, intervention type and early stopping (including reasons) as well as data on the use of causal evidence from secondary data for planned predictive enrichment.RESULTS: We screened 9020 records and included 316 unique RCTs with a total of 268,563 randomised participants. One hundred seventy-three (55%) trials tested drug interventions, 101 (32%) management strategies and 42 (13%) devices. The median duration of enrolment was 2.2 (IQR: 1.3-3.4) years, and 83% of trials randomised less than 1000 participants. Thirty-six trials (11%) were restricted to COVID-19 patients. Of the 55 (17%) trials that stopped early, 23 (42%) used predefined rules; futility, slow enrolment and safety concerns were the commonest stopping reasons. None of the included RCTs had used causal evidence from secondary data for planned predictive enrichment.CONCLUSION: Work is needed to harness the rich multiverse of critical care data and establish its utility in critical care RCTs. Such work will likely need to leverage methodology from interventional and analytical epidemiology as well as data science.
U2 - 10.1111/aas.14321
DO - 10.1111/aas.14321
M3 - Review
C2 - 37649412
VL - 68
SP - 16
EP - 25
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
SN - 0001-5172
IS - 1
ER -
ID: 366976449