Comparison of adaptive treatment strategies based on longitudinal outcomes in sequential multiple assignment randomized trials

• Published in: Statistics in medicine 2017-02, Vol.36 (3), p.403-415
• Main Author: Li, Zhiguo
• Format: Article
• Language: English
• Subjects: adaptive treatment strategy; Antipsychotic Agents - therapeutic use; Clinical outcomes; Clinical trials; Data Interpretation, Statistical; Estimating techniques; generalized estimating equation; generalized linear model; Generalized linear models; Humans; Linear Models; longitudinal data analysis; Longitudinal Studies; Medical treatment; Models, Statistical; piecewise linear model; Psychopharmacology; Psychotropic drugs; Randomized Controlled Trials as Topic - methods; Regression Analysis; Schizophrenia - drug therapy; sequential multiple assignment randomized trial; Statistics as Topic; Treatment Outcome
• ISSN: 0277-6715; 1097-0258
• DOI: 10.1002/sim.7136

In sequential multiple assignment randomized trials, longitudinal outcomes may be the most important outcomes of interest because this type of trials is usually conducted in areas of chronic diseases or conditions. We propose to use a weighted generalized estimating equation (GEE) approach to analyzing data from such type of trials for comparing two adaptive treatment strategies based on generalized linear models. Although the randomization probabilities are known, we consider estimated weights in which the randomization probabilities are replaced by their empirical estimates and prove that the resulting weighted GEE estimator is more efficient than the estimators with true weights. The variance of the weighted GEE estimator is estimated by an empirical sandwich estimator. The time variable in the model can be linear, piecewise linear, or more complicated forms. This provides more flexibility that is important because, in the adaptive treatment setting, the treatment changes over time and, hence, a single linear trend over the whole period of study may not be practical. Simulation results show that the weighted GEE estimators of regression coefficients are consistent regardless of the specification of the correlation structure of the longitudinal outcomes. The weighted GEE method is then applied in analyzing data from the Clinical Antipsychotic Trials of Intervention Effectiveness. Copyright © 2016 John Wiley & Sons, Ltd.