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Accounting for Behavior in Treatment Effects: New Applications for Blind Trials

Chassang, Sylvain and Snowberg, Erik and Seymour, Ben and Bowles, Cayley (2015) Accounting for Behavior in Treatment Effects: New Applications for Blind Trials. PLoS ONE, 10 (6). Art. No. e0127227. ISSN 1932-6203. PMCID PMC4465691.

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The double-blind randomized controlled trial (DBRCT) is the gold standard of medical research. We show that DBRCTs fail to fully account for the efficacy of treatment if there are interactions between treatment and behavior, for example, if a treatment is more effective when patients change their exercise or diet. Since behavioral or placebo effects depend on patients’ beliefs that they are receiving treatment, clinical trials with a single probability of treatment are poorly suited to estimate the additional treatment benefit that arises from such interactions. Here, we propose methods to identify interaction effects, and use those methods in a meta-analysis of data from blinded anti-depressant trials in which participant-level data was available. Out of six eligible studies, which included three for the selective serotonin re-uptake inhibitor paroxetine, and three for the tricyclic imipramine, three studies had a high (>65%) probability of treatment. We found strong evidence that treatment probability affected the behavior of trial participants, specifically the decision to drop out of a trial. In the case of paroxetine, but not imipramine, there was an interaction between treatment and behavioral changes that enhanced the effectiveness of the drug. These data show that standard blind trials can fail to account for the full value added when there are interactions between a treatment and behavior. We therefore suggest that a new trial design, two-by-two blind trials, will better account for treatment efficacy when interaction effects may be important.

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Additional Information:© 2015 Chassang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: December 22, 2014; Accepted: April 12, 2015; Published: June 10, 2015. This work was supported by NSF grant #1156154 (Sylvain Chassang and Erik Snowberg): Improving Randomized Controlled Trials: Practical and Theoretical Challenges. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Chassang and Snowberg acknowledge the support of NSF SES-1156154. We are grateful to Jay C. Fournier for sharing his data. Author Contributions: Conceived and designed the experiments: SC ES BS CB. Analyzed the data: SC ES BS CB. Wrote the paper: SC ES BS CB.
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PubMed Central ID:PMC4465691
Record Number:CaltechAUTHORS:20150611-082958774
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Official Citation:Chassang S, Snowberg E, Seymour B, Bowles C (2015) Accounting for Behavior in Treatment Effects: New Applications for Blind Trials. PLoS ONE 10(6): e0127227. doi:10.1371/journal.pone.0127227
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58176
Deposited By: Tony Diaz
Deposited On:11 Jun 2015 15:47
Last Modified:17 Aug 2016 17:53

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