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Estimating drug effects in the presence of placebo response: Causal inference using growth mixture modeling
Author(s) -
Muthén Bengt,
Brown Hendricks C.
Publication year - 2009
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.3721
Subject(s) - placebo , placebo response , drug , causal inference , inference , drug trial , medicine , mixture model , clinical trial , statistics , pharmacology , mathematics , artificial intelligence , computer science , alternative medicine , pathology
Placebo‐controlled randomized trials for antidepressants and other drugs often show a response for a sizeable percentage of the subjects in the placebo group. Potential placebo responders can be assumed to exist also in the drug treatment group, making it difficult to assess the drug effect. A key drug research focus should be to estimate the percentage of individuals among those who responded to the drug who would not have responded to the placebo (‘Drug Only Responders’). This paper investigates a finite mixture model approach to uncover percentages of up to four potential mixture components: Never Responders, Drug Only Responders, Placebo Only Responders, and Always Responders. Two examples are used to illustrate the modeling, a 12‐week antidepressant trial with a continuous outcome (Hamilton D score) and a 7‐week schizophrenia trial with a binary outcome (illness level). The approach is formulated in causal modeling terms using potential outcomes and principal stratification. Growth mixture modeling (GMM) with maximum‐likelihood estimation is used to uncover the different mixture components. The results point to the limitations of the conventional approach of comparing marginal response rates for drug and placebo groups. It is useful to augment such reporting with the GMM‐estimated prevalences for the four classes of subjects and the Drug Only Responder drug effect estimate. Copyright © 2009 John Wiley & Sons, Ltd.