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Am J Respir Crit Care Med. 2014 Jun 15;189(12):1469-78. doi: 10.1164/rccm.201401-0056CP.

Outcomes and statistical power in adult critical care randomized trials.

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1
1 Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics.

Abstract

RATIONALE:

Intensive care unit (ICU)-based randomized clinical trials (RCTs) among adult critically ill patients commonly fail to detect treatment benefits.

OBJECTIVES:

Appraise the rates of success, outcomes used, statistical power, and design characteristics of published trials.

METHODS:

One hundred forty-six ICU-based RCTs of diagnostic, therapeutic, or process/systems interventions published from January 2007 to May 2013 in 16 high-impact general or critical care journals were studied.

MEASUREMENT AND MAIN RESULTS:

Of 146 RCTs, 54 (37%) were positive (i.e., the a priori hypothesis was found to be statistically significant). The most common primary outcomes were mortality (n = 40 trials), infection-related outcomes (n = 33), and ventilation-related outcomes (n = 30), with positive results found in 10, 58, and 43%, respectively. Statistical power was discussed in 135 RCTs (92%); 92 cited a rationale for their power parameters. Twenty trials failed to achieve at least 95% of their reported target sample size, including 11 that were stopped early due to insufficient accrual/logistical issues. Of 34 superiority RCTs comparing mortality between treatment arms, 13 (38%) accrued a sample size large enough to find an absolute mortality reduction of 10% or less. In 22 of these trials the observed control-arm mortality rate differed from the predicted rate by at least 7.5%.

CONCLUSIONS:

ICU-based RCTs are commonly negative and powered to identify what appear to be unrealistic treatment effects, particularly when using mortality as the primary outcome. Additional concerns include a lack of standardized methods for assessing common outcomes, unclear justifications for statistical power calculations, insufficient patient accrual, and incorrect predictions of baseline event rates.

KEYWORDS:

critical care; intensive care; intensive care unit; randomized clinical trial; randomized controlled trial

PMID:
24786714
PMCID:
PMC4226016
DOI:
10.1164/rccm.201401-0056CP
[Indexed for MEDLINE]
Free PMC Article
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