Alternative methods for testing treatment effects on the basis of multiple outcomes: simulation and case study

Stat Med. 2011 Jul 20;30(16):1917-32. doi: 10.1002/sim.4262. Epub 2011 May 3.

Abstract

In clinical trials multiple outcomes are often used to assess treatment interventions. This paper presents an evaluation of likelihood-based methods for jointly testing treatment effects in clinical trials with multiple continuous outcomes. Specifically, we compare the power of joint tests of treatment effects obtained from joint models for the multiple outcomes with univariate tests based on modeling the outcomes separately. We also consider the power and bias of tests when data are missing, a common feature of many trials, especially in psychiatry. Our results suggest that joint tests capitalize on the correlation of multiple outcomes and are more powerful than standard univariate methods, especially when outcomes are missing completely at random. When outcomes are missing at random, test procedures based on correctly specified joint models are unbiased, while standard univariate procedures are not. Results of a simulation study are reported, and the methods are illustrated in an example from the Clinical Antipsychotic Trials of Intervention Effectiveness for schizophrenia.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Biostatistics / methods*
  • Clinical Trials as Topic / statistics & numerical data
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / therapeutic use
  • Humans
  • Likelihood Functions
  • Linear Models
  • Metabolic Syndrome / etiology
  • Models, Statistical
  • Multivariate Analysis
  • Outcome Assessment, Health Care / statistics & numerical data*
  • Perphenazine / adverse effects
  • Perphenazine / therapeutic use
  • Quetiapine Fumarate
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Schizophrenia / drug therapy
  • Treatment Outcome*

Substances

  • Antipsychotic Agents
  • Dibenzothiazepines
  • Quetiapine Fumarate
  • Perphenazine