Blinding Assessment and the Placebo Effect: A Causal Inference Perspective

• Activity Number: 518
• Type: Topic Contributed
• Date/Time: Wednesday, August 7, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Zhiwei Zhang*+ and Richard Kotz and Chenguang Wang and Shiling Ruan and Martin P. Ho
• Companies: Food and Drug Administration and Food and Drug Administration and Johns Hopkins University and Food and Drug Administration and FDA/CDRH
• Keywords: blinding ; causal inference ; confounding ; counterfactual ; placebo effect ; potential outcome

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 mentality with regard to the treatment received (or treatmentality, for brevity), making it difficult to interpret the usual treatment comparison 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.