title: Alternative methods for testing treatment effects on the basis of multiple outcomes: simulation and case study.
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.
authors.affiliation: Harvard Medical School, Boston, MA, USA. yoon@hcp.med.harvard.edu
authors.forename: Frank B
authors.initials: FB
authors.lastname: Yoon
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Fitzmaurice
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Lipsitz
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Horton
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Sharon-Lise T
authors.initials: SL
authors.lastname: Normand
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D056808:Biostatistics / Q000379:methods*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D024821:Metabolic Syndrome / Q000209:etiology; D015233:Models, Statistical; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D010546:Perphenazine / Q000009:adverse effects / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D010546:Perphenazine