A repeated measures model for analysis of continuous outcomes in sequential parallel comparison design studies.
Previous authors have proposed the sequential parallel comparison design (SPCD) to address the issue of high placebo response rate in clinical trials. The original use of SPCD focused on binary outcomes, but recent use has since been extended to continuous outcomes that arise more naturally in many fields, including psychiatry. Analytic methods proposed to date for analysis of SPCD trial continuous data included methods based on seemingly unrelated regression and ordinary least squares. Here, we propose a repeated measures linear model that uses all outcome data collected in the trial and accounts for data that are missing at random. An appropriate contrast formulated after the model has been fit can be used to test the primary hypothesis of no difference in treatment effects between study arms. Our extensive simulations show that when compared with the other methods, our approach preserves the type I error even for small sample sizes and offers adequate power and the smallest mean squared error under a wide variety of assumptions. We recommend consideration of our approach for analysis of data coming from SPCD trials.
Department of Biostatistics, Boston University, 801 Massachusetts Avenue, Boston, MA 02118, USA. doros@bu.edu
Gheorghe
G
Doros
Michael
M
Pencina
Denis
D
Rybin
Allison
A
Meisner
Maurizio
M
Fava
D014150:Antipsychotic Agents / Q000627:therapeutic use; D000068180:Aripiprazole; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003198:Computer Simulation; D003865:Major Depressive Disorder / Q000188:drug therapy; D006801:Humans; D016014:Linear Models; D010879:Piperazines / Q000627:therapeutic use; D015990:Placebo Effect; D015363:Quinolones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole