Only Skin Deep: Optimism and Public Self-Consciousness Did Not Associate With the Placebo Response in a Dermatology Clinical Trial
June 2014 | Volume 13 | Issue 6 | Original Article | 719 | Copyright © June 2014
Marisa Kardos Garshick MD,a Anne Lynn S. Chang MD,b and Alexandra Boer Kimball MD MPHa
aDepartment of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
bDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA
OBJECTIVE: Although not well-understood, dermatologic diseases studied in clinical trials often demonstrate substantial response to placebo. The study objective is to determine if optimism, public self-consciousness and other personality traits predict response to placebo or active treatment in a dermatology clinical trial.
METHODS: A questionnaire was mailed to subjects previously enrolled in a two-center rosacea study who had been randomized to either a treatment or placebo gel. The questionnaire included the Revised Life Orientation Test (LOT-R), the Public Self-Consciousness Scale, and questions to assess personality traits.
RESULTS: Forty-seven subjects out of 83 (57%) returned the questionnaire. There was no statistically significant difference in the LOT-R score in those who responded to placebo versus those who did not (18.08 vs 17.92, P
= 0.92) nor in those who responded to active treatment versus those who did not (16.27 vs 15.86, P
= 0.79). There was no statistically significant difference in public-self consciousness among placebo or active treatment responders versus non-responders (11.75 vs 10.67, P
=0.66; 13.55 vs 14.45, P
= 0.68). The placebo responders were more likely to report that they were not unusually sensitive to most drugs/medications (X2= 8.33, P
CONCLUSION: Although this pilot study is small, there was no meaningful difference in levels of optimism or public self-consciousness among those who responded to placebo. Placebo responders were more likely to report that they were not sensitive to most drugs/medications, raising the possibility that they are actually less likely to detect when they are on medications. J Drugs Dermatol.
In clinical trials, the placebo has an essential role as a comparison set point for various therapies and drugs. Moreover, the placebo response ultimately determines how randomized controlled trials are interpreted. With time, the role of the placebo has expanded beyond its role in clinical trials and has been reported to be responsible for beneficial outcomes in many areas of medicine.1 Despite many years of research, what accounts for why certain individuals exhibit a placebo response is still unclear.
Prior studies have examined how personality and expectations influence the placebo effect in patients with pain and irritable bowel syndrome (IBS).2,3 For example, in one study investigating placebo analgesia, high dispositional optimism and low state anxiety were found to be significant predictors of placebo response,2 while in individuals with IBS, extraversion was reported to be an independent predictor of placebo response.3 However, to date, no reports directly address dermatologic patients. Despite the seemingly objective nature of dermatologic diseases graded on the appearance of the skin, previously reported randomized controlled trials have demonstrated substantial placebo responses in dermatology patients. In clinical trials for psoriasis studying systemic medications, 6-33% of placebo groups had a 50% reduction in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment.4-8 Interestingly, even in acne trials using an oral contraceptive, drospirenone/ethinyl estradiol, where it might be difficult to maintain patient blinding, double-blind randomized placebo-controlled trial reported a 30% reduction in total acne lesions in the placebo group as assessed by investigators.9 Furthermore, in a trial for doxycycline for rosacea, 26% of the placebo group achieved a 2-point or greater improvement in investigator global assessment scoring.10
Topical studies in dermatology are particularly interesting because not only could there be a placebo effect, but there is also a vehicle effect that may increase the response rates in populations on placebo topical treatments. We wanted to determine if there were predictive personality traits that might be helpful in improving study design and screening of subjects. We therefore designed a study to investigate the role of optimism, self-consciousness and personality traits on the placebo effect in dermatology patients. To test this hypothesis, we examined whether those individuals who respond to placebo, among dermatologic research subjects, are more optimistic and self-conscious.