The Fragility and Reliability of Conclusions of Anesthesia and Critical Care Randomized Trials With Statistically Significant Findings: A Systematic Review*

Abstract

Objectives: The Fragility Index, which represents the number of patients responsible for a statistically significant finding, has been suggested as an aid for interpreting the robustness of results from clinical trials. A small Fragility Index indicates that the statistical significance of a trial depends on only a few events. Our objectives were to calculate the Fragility Index of statistically significant results from randomized controlled trials of anesthesia and critical care interventions and to determine the frequency of distorted presentation of results or “spin”. Data Sources: We systematically searched MEDLINE from January 01, 2007, to February 22, 2017, to identify randomized controlled trials exploring the effect of critical care medicine or anesthesia interventions. Study Selection: Studies were included if they randomized patients 1:1 into two parallel arms and reported at least one statistically significant (p < 0.05) binary outcome (primary or secondary). Data Extraction: Two reviewers independently assessed eligibility and extracted data. The Fragility Index was determined for the chosen outcome. We assessed the level of spin in negative trials and the presence of recommendations for clinical practice in positive trials. Data Synthesis: We identified 166 eligible randomized controlled trials with a median sample size of 207 patients (interquartile range, 109–497). The median Fragility Index was 3 (interquartile range, 1–7), which means that adding three events to one of the trials treatment arms eliminated its statistical significance. High spin was identified in 42% (n = 30) of negative randomized controlled trials, whereas 21% (n = 20) of positive randomized controlled trials provided recommendations. Lower levels of spin and recommendations were associated with publication in journals with high impact factors (p < 0.001 for both). Conclusions: Statistically significant results in anesthesia and critical care randomized controlled trials are often fragile, and study conclusions are frequently affected by spin. Routine calculation of the Fragility Index in medical literature may allow for better understanding of trials and therefore enhance the quality of reporting.

Statistical fragility of randomized clinical trials in shoulder arthroplasty

“…In addition, the National Institutes of Health iCite database (Bethesda, MD, USA) was used to identify the RCR for each included study. 8,11…”

“…32 To address this concern, many authors have advocated the broader use of alternative statistical methods to evaluate clinical data. 7,8,22,26,31 One proposed alternative tool is the Fragility Index (FI), defined as the number of patients, if given an alternative result, that would be sufficient to change the statistical significance of a study outcome. The FI is calculated through the stepwise alteration of an outcome in a study arm until the recalculated P value changes from significant to insignificant or vice versa.…”

The Statistical Fragility of Single-Bundle vs Double-Bundle Autografts for ACL Reconstruction: A Systematic Review of Comparative Studies

“…It has been shown to be malleable to study design, randomization, and study power. 18 Importantly, significance can be altered by a small number of event reversals within a sample, 17 , 23 , 30 , 44 and the intent of amalgamated data analyzed by systematic reviews as well as meta-analyses is to mitigate the statistical lability of any single study. If the number of event reversals required to alter significance is less than the number of patients lost to follow-up, 45 it could be possible for studies to have altered findings simply by maintaining follow-up.…”

Fragility Index and Fragility Quotient in Randomized Controlled Trials on Corticosteroids in ARDS Due to COVID-19 and Non-COVID-19 Etiology

“…Studies with a higher FI are considered more robust [4,5] and may assist the clinicians to interpret the results of their findings [6]. Many RCTs in anesthesiology and critical care reported fragile results with inconsistent conclusions [7]. We focused on RCTs regarding two major fields of critical care research such as ARDS and COVID-19 and applied this new statistical methodology to investigate the role of corticosteroids in these two clinical settings.…”