Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Calibrated use of deception in assessing the placebo effect

  • Alberto J Espay, Principal Investigator, University of Cincinnatiaespay@gmail.com
  • Alok Dwivedi, El Paso, TX; Anthony E. Lang, Toronto, CA; Michael J. Linke, Cincinnati, OH; Jerzy P. Szaflarski, Birmingham, AL
Submitted February 11, 2015

We thank editorialists Drs. LeWitt and Kim [1] and WriteClick submitter Dr. Kelley for their thoughtful feedback on our clinical trial examining the effect of cost on the placebo response. [2] We welcome the discussion on alternative explanations of our results and embrace the suggestions of exploring "authorized deception" as a tool to incorporate into future trials. We also agree that an independent party should collect post-debriefing data on issues of trust, justification of research, and willingness to participate in future studies from subjects participating in studies involving deception.

Given the number of additional issues raised by Drs. LeWitt, Kim, and Kelley, we have itemized our response here:

(1) Low sample size. We calculated the power needed to show significant differences between groups as 12. With a larger sample size, the magnitude of statistical significance would have increased rather than decreased without adding any more validity to the findings.

(2) Results were confounded by "treatment by period effect." It is noteworthy that ignoring the second period data also demonstrated a 10% greater improvement in the "expensive" compared to the "cheap" placebo. Stratified analysis by order showed 14% improvement in "expensive" placebo when this placebo was administered first compared to the "cheap" placebo and 7% improvement when cheap placebo was administered first.

(3) $100 per dose was considered "cheap" relative to the $1,500 dose. Subjects learned the price of both interventions at the outset. While $100 might never be "cheap" for a single treatment, it is compared to a similar intervention costing 15 times more.

(4) While the "cheap" placebo significantly improved motor function, such improvement was also significantly lower than that of levodopa. On the other hand, the magnitude of benefit of the "expensive" placebo was not significantly lower than that of levodopa (admittedly, a larger sample would have been expected to show a difference). These findings suggest that both are useful to establish therapeutic effect of a treatment in placebo controlled trial but cost-matched placebo may provide a more appropriate efficacy comparator for a treatment.

(5) Our study does not advocate for the use of placebo in general practice. It advocates for the interpretation of these findings as suggestive that there is an untapped opportunity to magnify the magnitude of benefits of standard interventions by enhancing their perception of efficacy.

(6) The implications to the threat to the physician-patient relationship are discussed in the original article. All patients were from the lead author's own clinic (per IRB request) and all have remained his patients after the study. Debriefing them about the nature of the study did not end the patient-physician relationship and did not prevent their engagement in other clinical research opportunities (half of them have enrolled since in other studies). They understood that the scientific question being probed required the calibrated use of deception.

1. LeWitt PA, Kim S. The pharmacodynamics of placebo: Expectation effects of price as a proxy for efficacy. Neurology 2015;84:1-2.

2. Espay AJ, Norris MM, Eliassen JC, Dwivedi A, Smith MS, Banks C, et al. Placebo effect of medication cost in parkinson disease: A randomized double-blind study. Neurology 2015; 0: WNL.0000000000001282v1-101212000

For disclosures, contact the editorial office at journal@neurology.org.

Navigate back to article

Neurology: 100 (5)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise