A causal model for joint evaluation of placebo and treatment-specific effects in clinical trials

Zhiwei Zhang, Richard M. Kotz, Chenguang Wang, Shiling Ruan, Martin Ho

Research output: Contribution to journalArticlepeer-review

Abstract

Evaluation of medical treatments is frequently complicated by the presence of substantial placebo effects, especially on relatively subjective endpoints, and the standard solution to this problem is a randomized, double-blinded, placebo-controlled clinical trial. However, effective blinding does not guarantee that all patients have the same belief or mentality about which treatment they have received (or treatmentality, for brevity), making it difficult to interpret the usual intent-to-treat effect as a causal effect. We discuss the causal relationships among treatment, treatmentality and the clinical outcome of interest, and propose a causal model for joint evaluation of placebo and treatment-specific effects. The model highlights the importance of measuring and incorporating patient treatmentality and suggests that each treatment group should be considered a separate observational study with a patient's treatmentality playing the role of an uncontrolled exposure. This perspective allows us to adapt existing methods for dealing with confounding to joint estimation of placebo and treatment-specific effects using measured treatmentality data, commonly known as blinding assessment data. We first apply this approach to the most common type of blinding assessment data, which is categorical, and illustrate the methods using an example from asthma. We then propose that blinding assessment data can be collected as a continuous variable, specifically when a patient's treatmentality is measured as a subjective probability, and describe analytic methods for that case.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalBiometrics
Volume69
Issue number2
DOIs
StatePublished - Jun 2013

Keywords

  • Blinding
  • Causal inference
  • Confounding
  • Counterfactual
  • Placebo effect
  • Potential outcome

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Fingerprint Dive into the research topics of 'A causal model for joint evaluation of placebo and treatment-specific effects in clinical trials'. Together they form a unique fingerprint.

Cite this