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Commercial Features of Placebo and Therapeutic Efficacy
To the Editor: It is possible that the therapeutic efficacy of medications is affected by commercial features such as lower prices. Because such features influence patients' expectations,1 they may play an unrecognized therapeutic role by influencing the efficacy of medical therapies, especially in conditions associated with strong placebo responses.2-3 To investigate this possibility, we studied the effect of price on analgesic response to placebo pills.
Methods
In 2006 we recruited 82 healthy paid volunteers in Boston, Massachusetts, using an online advertisement. Each participant was informed by brochure about a (purported) new opioid analgesic approved by the Food and Drug Administration; it was described as similar to codeine with faster onset time, but it was actually a placebo pill. After randomization, half of the participants were informed that the drug had a regular price of $2.50 per pill and half that the price had been discounted to $0.10 per pill (no reason for the discount was mentioned). All participants received identical placebo pills and were paid $30. Participants were blinded to the study purpose, and researchers were blinded to group assignment. The study was approved by the Massachusetts Institute of Technology institutional review board, and all participants provided written informed consent and were debriefed after the study.
The protocol followed an established approach for studying pain.4 Electrical shocks to the wrist were calibrated to each participant's pain tolerance. After calibration, participants received the test shocks, rating the pain on a computerized visual analog scale anchored by the labels "no pain at all" and "the worst pain imaginable." Participants received all possible shocks in 2.5-V increments between 0 V and their calibrated tolerance. Stimulation at each intensity level was carried out twice for each participant (before and after taking the pill), and the change in reaction to the stimulation was assessed. Visual analog scale ratings were converted to a 100-point scale, the postpill score for each voltage was subtracted from the prepill score, and the mean of these differences was calculated for each participant.
The percentage of participants experiencing a mean score reduction vs increase was compared between the 2 groups using a 2-tailed  2 test. Because stronger pain may be associated with stronger placebo responses,5 we also compared results for the 50% most painful shocks for each participant. In addition, mean differences at each voltage between the 2 groups were compared overall with a sign test and individually with F tests. A P value of .05 was considered statistically significant. Analyses were performed using SPSS version 15 (SPSS Inc, Chicago, Illinois).
Results
Patient characteristics are shown in the Table. In the regular-price group, 85.4% (95% confidence interval [CI], 74.6%-96.2%) of the participants experienced a mean pain reduction after taking the pill, vs 61.0% (95% CI, 46.1%-75.9%) in the low-price (discounted) group (P = .02). Similar results occurred when analyzing only the 50% most painful shocks for each participant (80.5% [95% CI, 68.3%-92.6%] vs 56.1% [95% CI, 40.9%-71.3%], respectively; P = .03).
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Table. Comparison of Participants Assigned to Regular-Price Placebo vs Low-Price (Discounted) Placebo
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Considering all voltages tested, pain reduction was greater for the regular-price pill (P < .001). In addition, for 26 of 29 intensities (from 10 to 80 V), mean pain reduction was greater for the regular-price pill (Figure).
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Figure. Pain Ratings by Voltage Intensity
Mean difference in pain ratings, after vs before placebo, by voltage intensity. Higher value indicates greater pain reduction. The table depicts the intensity of the shocks and the number of observations in the regular-price and low-price conditions. P value is less than .05 for the shock intensities 27.5 V through 30.0 V, 35.0 V through 75.0 V, and 80.0 V.
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Comment
These results are consistent with described phenomena of commercial variables affecting quality expectations1 and expectations influencing therapeutic efficacy.4 Placebo responses to commercial features have many potential clinical implications. For example, they may help explain the popularity of high-cost medical therapies (eg, cyclooxygenase 2 inhibitors) over inexpensive, widely available alternatives (eg, over-the-counter nonsteroidal anti-inflammatory drugs) and why patients switching from branded medications may report that their generic equivalents are less effective. Studies of real-world effectiveness may be more generalizable if they reflect how medications are sold in addition to how they are formulated. Furthermore, clinicians may be able to harness quality cues in beneficial ways,6 for example, by de-emphasizing potentially deleterious commercial factors (eg, low-priced, generic).
These findings need to be replicated in broader populations and clinical settings to better understand how communicating quality cues with patient populations can maximize treatment benefits and patient satisfaction.
Author Contributions: Dr Ariely had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Waber, Shiv, Carmon, Ariely.
Acquisition of data: Waber.
Analysis and interpretation of data: Waber, Ariely.
Drafting of the manuscript: Waber, Shiv, Ariely.
Critical revision of the manuscript for important intellectual content: Waber, Shiv, Carmon, Ariely.
Statistical analysis: Waber, Ariely.
Obtained funding: Ariely.
Administrative, technical, or material support: Waber.
Study supervision: Ariely.
Financial Disclosures: None reported.
Funding/Support: This study was funded by the Massachusetts Institute of Technology.
Role of the Sponsor: The sponsor had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of data; or the preparation, review, or approval of the manuscript.
Additional Contributions: Taya Leary, MS, Tom Pernikoff, BS, and John Keefe, BS, all with the Massachusetts Institute of Technology at the time of this study, provided assistance in data collection. Mr Keefe received compensation for this role. Andrew Lippman, PhD, Massachusetts Institute of Technology, provided logistical support and Mark Vangel, PhD, Massachusetts General Hospital, provided statistical assistance. Neither received compensation for these roles.
Rebecca L. Waber, BS
Massachusetts Institute of Technology
Cambridge, Massachusetts
Baba Shiv, PhD
Stanford University
Stanford, California
Ziv Carmon, PhD
INSEAD
Singapore
Dan Ariely, PhD
ariely{at}mit.edu
Massachusetts Institute of Technology
1. Rao AR, Monroe KB. The effect of price, brand name, and store name on buyers' perceptions of product quality. J Marketing Res. 1989;26(3):351-357.
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2. Benedetti F. How the doctor's words affect the patient's brain. Eval Health Prof. 2002;25(4):369-386.
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3. Koshi EB, Short CA. Placebo theory and its implications for research and clinical practice. Pain Pract. 2007;7(1):4-20.
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4. Berns GS, Chappelow MC, Zink CF, Pagnoni G, Martin-Skurski ME. Neurobiological substrates of dread. Science. 2006;312(5774):754-758.
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5. Price DD, Fields HL. The contribution of desire and expectation to placebo analgesia: implications for new research strategies. In: Harrington A, ed. The Placebo Effect: An Interdisciplinary Exploration. Cambridge, Massachusetts: Harvard University Press; 1999:118-119.6. Gracely RH, Dubner R, Deeter WR, Wolskee PJ. Clinicians' expectations influence placebo analgesia. Lancet. 1985;1(8419):43.
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Letters Section Editor: Robert M. Golub, MD, Senior Editor.
JAMA. 2008;299(9):1016-1017.
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