Patient reported outcome measures in clinical trials should be initially analyzed as continuous outcomes for statistical significance and responder analyses should be reserved as secondary analyses

J Clin Epidemiol. 2021 Jun:134:95-102. doi: 10.1016/j.jclinepi.2021.01.026. Epub 2021 Feb 6.

Abstract

Objective: To evaluate the power of responder analyses in a randomized controlled trial.

Study design and setting: Simulations were based on the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), which compared sertraline to placebo for the treatment of depression in kidney disease. Baseline disease severity, placebo response, effect size, and the proportion of responders were varied across 72 scenarios. Power was assessed using a t-test for change scores, and the chi-square test for dichotomized outcomes of the minimal important difference (MID), improvement and remission in 10,000 datasets with a fixed sample size of 193.

Results: The t-test had >80% power except for scenarios with the lowest sertraline effect size. The chi-square test using the MID had <7% power in all scenarios while improvement and remission of achieved >80% power only at higher effect sizes and/or when the proportion of responders was highest at 0.5. The chi-square test for improvement had marginal power increases compared to the t-test (4/72 scenarios = 5.6%) and that for remission did not outperform the t-test in any scenario.

Conclusions: The t-test outperforms the chi-square test for dichotomized outcomes regardless of baseline disease severity, placebo response, effect size and the proportion of responders to the intervention.

Keywords: Dichotomization; Patient reported outcome measures; Power; Responder analyses; Responder analysis; Simulation.

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Computer Simulation
  • Depression / drug therapy*
  • Depression / etiology
  • Humans
  • Linear Models
  • Models, Statistical
  • Patient Reported Outcome Measures*
  • Randomized Controlled Trials as Topic / methods*
  • Renal Insufficiency, Chronic / psychology*
  • Sample Size
  • Treatment Outcome

Substances

  • Antidepressive Agents