Prevalence and Implications of Significance Testing for Baseline Covariate Imbalance in Randomised Cancer Clinical Trials: The Table 1 Fallacy

Authors

Alexander D Sherry
Pavlos Msaouel
Zachary R McCaw
Joseph Abi Jaoude
Eric J Hsu
Ramez Kouzy
Roshal Patel
Yumeng Yang
Timothy A Lin
Cullen M Taniguchi
Claus Rödel
Emmanouil Fokas
Chad Tang
Clifton David Fuller
Bruce Minsky
Tomer Meirson
Ryan Sun
Ethan B Ludmir

Publication Date

11-1-2023

Journal

The European Journal of Cancer

Abstract

Background: The 'Table 1 Fallacy' refers to the unsound use of significance testing for comparing the distributions of baseline variables between randomised groups to draw erroneous conclusions about balance or imbalance. We performed a cross-sectional study of the Table 1 Fallacy in phase III oncology trials.

Methods: From ClinicalTrials.gov, 1877 randomised trials were screened. Multivariable logistic regressions evaluated predictors of the Table 1 Fallacy.

Results: A total of 765 randomised controlled trials involving 553,405 patients were analysed. The Table 1 Fallacy was observed in 25% of trials (188 of 765), with 3% of comparisons deemed significant (59 of 2353), approximating the typical 5% type I error assertion probability. Application of trial-level multiplicity corrections reduced the rate of significant findings to 0.3% (six of 2345 tests). Factors associated with lower odds of the Table 1 Fallacy included industry sponsorship (adjusted odds ratio [aOR] 0.29, 95% confidence interval [CI] 0.18-0.47; multiplicity-corrected P < 0.0001), larger trial size (≥795 versus <280 patients; aOR 0.32, 95% CI 0.19-0.53; multiplicity-corrected P = 0.0008), and publication in a European versus American journal (aOR 0.06, 95% CI 0.03-0.13; multiplicity-corrected P < 0.0001).

Conclusions: This study highlights the persistence of the Table 1 Fallacy in contemporary oncology randomised controlled trials, with one of every four trials testing for baseline differences after randomisation. Significance testing is a suboptimal method for identifying unsound randomisation procedures and may encourage misleading inferences. Journal-level enforcement is a possible strategy to help mitigate this fallacy.

Keywords

Humans, Prevalence, Cross-Sectional Studies, Neoplasms, Randomized Controlled Trials as Topic

DOI

10.1016/j.ejca.2023.113357

PMID

37827064

PMCID

PMC11512581

PubMedCentral® Posted Date

11-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes