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

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  • Sylvain Chassang
  • Erik Snowberg
  • Ben Seymour
  • Cayley Bowles

Abstract

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.

Suggested Citation

  • Sylvain Chassang & Erik Snowberg & Ben Seymour & Cayley Bowles, 2015. "Accounting for Behavior in Treatment Effects: New Applications for Blind Trials," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-13, June.
    • Handle: RePEc:plo:pone00:0127227
    DOI: 10.1371/journal.pone.0127227
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    References listed on IDEAS

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    Cited by:

    1. Abhijit Banerjee & Sylvain Chassang & Erik Snowberg, 2016. "Decision Theoretic Approaches to Experiment Design and External Validity," NBER Working Papers 22167, National Bureau of Economic Research, Inc.
    2. Marcelo Arbex & Justin M. Carre & Shawn N. Geniole & Enlinson Mattos, 2018. "Testosterone, personality traits and tax evasion," Working Papers 1801, University of Windsor, Department of Economics.
    3. Bulte, Erwin & Di Falco, Salvatore & Lensink, Robert, 2020. "Randomized interventions and “real” treatment effects: A cautionary tale and an example," World Development, Elsevier, vol. 127(C).
    4. Hennessy, Christopher A. & Chemla, Gilles, 2022. "Signaling, instrumentation, and CFO decision-making," Journal of Financial Economics, Elsevier, vol. 144(3), pages 849-863.
    5. Chemla, Gilles & Hennessy, Christopher A., 2019. "Controls, belief updating, and bias in medical RCTs," Journal of Economic Theory, Elsevier, vol. 184(C).
    6. Arbex, Marcelo Aarestru & Carré, Justin M. & Geniole, Shawn N. & Mattos, Enlinson, 2018. "Tax evasion, testosterone and personality traits," Textos para discussão 466, FGV EESP - Escola de Economia de São Paulo, Fundação Getulio Vargas (Brazil).

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