Critical Care Randomized Trials Demonstrate Power Failure: A Low Positive Predictive Value of Findings in the Critical Care Research Field

Abstract

Background We aimed to determine the post-hoc power of randomized controlled trials (RCTs) in critical care, and describe the implications for long-term positive (PPV) and negative predictive value (NPV) of statistically significant and non-significant findings respectively in the research field. Methods We reviewed three cohorts of RCTs. “Adult-RCTs” were 216 multicenter RCTs with a mortality outcome from a published systematic review. “Pediatric-RCTs” were 120 RCTs with a mortality outcome, obtained by search of picutrials.net. “Consecutive-RCTs” were 90 recent RCTs obtained by screening publications in 6 journals. Post-hoc power for each study was calculated at α 0.05 and 0.005, for measures of small, medium, and large effect-size, using G*Power software. Long-run expected PPV and NPV of critical care research field findings were then calculated. Results With α 0.05, post-hoc power for small effect-size was very low in all RCT-cohorts (eg, median 24% in Adult-RCTs). For medium effect-size, post-hoc power was low, except for Adult-RCTs (eg, median 9% in Pediatric-RCTs). For large effect-size, post-hoc power for non-human-animal Consecutive-RCTs was low (median 32%). With α 0.005, post-hoc power was even lower. The corollary was that both PPV and NPV were poor for small effect-size, unless α 0.005 was used. Even with α 0.005, with realistic (vs. optimistic) prior probability of the alternative hypothesis, the PPV was low (eg, in Adult-RCTs 57.1% vs. 92.3%). Adding mild bias (0.1) reduced the PPV even further. For medium effect-size both PPV and NPV were better; nevertheless, with α 0.05 and realistic prior probability of the alternative hypothesis the PPV was poor, and with α 0.005 and mild bias (0.1) the PPV was very low (eg, Adult-RCTs median 44.1%). Conclusions To improve the predictive value of findings in the critical care research field, RCTs should be designed to have 80% power for realistic effect-size at α 0.005.