The Need for Large Clinical Studies in Perioperative Medicine

Replicability, Reproducibility, and Fragility of Research Findings—Ultimately, Caveat Emptor

“…Consequently, very large sample sizes of upward of 10,000 are needed to demonstrate statistical significance for a clinically important observed treatment effect. 21,22 As first reported in 2005 by Ioannidis, 23 initially stronger observed and subsequently contradictory treatment effects are not unusual in highly cited research of clinical interventions and their outcomes. A subsequent 2014 study by Ioannidis and colleagues 24 identified only 37 published reanalyses of randomized controlled trials, with 35% of these reporting salient findings and conclusions different from those of the original article.…”

“…14 THE FRAGILITY OF FINDINGS Ioannidis 7 has proposed "large-scale collaborative research" ( Table 2). Devereaux et al 21 trial size, (2) factorial randomization, and (3) composite outcomes. Although all 3 are relevant to the present discussion, we focus here on trial size.…”

“…22 However, a large sample presents the limitations of greater cost, longer data-acquisition periods, and possibly needing multiple collaborating centers. 21,22 Historically, small-scale randomized controlled trials, with a total sample size of 60 to 100, have been commonly published in the anesthesia, critical care, and pain medicine literature. With many complex, multifactorial, perioperative conditions, however, only a moderate treatment effect size or relative risk reduction of 15% to 30% can be expected with a single intervention.…”

“…With many complex, multifactorial, perioperative conditions, however, only a moderate treatment effect size or relative risk reduction of 15% to 30% can be expected with a single intervention. 21,22 Furthermore, very clinically important, dichotomous perioperative complications (e.g., myocardial infarction, stroke, acute renal failure, sepsis, and death) occur at low event rates. Consequently, very large sample sizes of upward of 10,000 are needed to demonstrate statistical significance for a clinically important observed treatment effect.…”

Bispectral Index versus Minimum Alveolar Concentration for Prevention of Intraoperative Awareness

“…2 This study is of particular interest for two reasons. As recently pointed out in an editorial by Devereaux et al,3 studies of this large size are required to study low-incidence outcomes with sufficient confidence in the statistical significance of results. In addition, this protocol incorporated the high standards demanded for CER, including the assessment of effectiveness, efficacy, and efficiency.…”