Archives of Dermatological Research

, Volume 304, Issue 9, pp 707–717

Placebo response in relation to clinical trial design: a systematic review and meta-analysis of randomized controlled trials for determining biologic efficacy in psoriasis treatment

  • Sonia A. Lamel
  • Kaley A. Myer
  • Naji Younes
  • James A. Zhou
  • Hilda Maibach
  • Howard I. Maibach
Original Paper


There is a need to better define how the efficacy of investigational drugs is affected by study design, implementation, and placebo responses in randomized controlled trials. The improvements observed in placebo groups within trials examining psoriasis treatments may be partially due to study design and implementation. We conducted a systematic review of randomized placebo-controlled trials assessing the efficacy of biologics in the treatment of psoriasis and psoriatic arthritis to evaluate rates of placebo and active drug responders to determine specific factors within study design that may contribute to placebo responses. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, ustekinumab, alefacept, and efalizumab that utilized Psoriasis Area Severity Index as an outcomes measure. We compared the rates of the placebo treatment arm versus the active drug arm achieving 75 % improvement of Psoriasis Area Severity Index. 31 trials involving 8285 active treatment and 3999 placebo patients were included. Rates of placebo responders (4.14 %) were significantly lower than active drug responders (48.4 %). The overall odds ratio calculated was 23.94 (p < 0.0001, 95 % CI 16.02–35.76). Binomial regression models showed that treatment indication, randomization fraction, a PASI inclusion requirement, and the time period of outcomes measure documentation affect placebo responses. Placebo responses seen in randomized controlled trials evaluating biologics in the treatment of psoriasis are not likely due to a physiologic mechanism, but may be secondary to chronic disease course and factors of clinical trial design and implementation.


Randomized controlled trial Study design Placebo effect Placebo response Psoriasis Psoriatic arthritis 



Every other week


Classification and tree


Every other week


Investigator global assessment






Psoriasis Area Severity Index


75 % improvement in Psoriasis Area Severity Index


Physician global assessment


Psoriatic arthritis




Four times weekly


Every week


Randomized controlled trial




Tumor necrosis factor


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Sonia A. Lamel
    • 1
  • Kaley A. Myer
    • 1
  • Naji Younes
    • 2
  • James A. Zhou
    • 2
  • Hilda Maibach
    • 2
  • Howard I. Maibach
    • 1
  1. 1.Department of Dermatology, San Francisco School of MedicineUniversity of CaliforniaSan FranciscoUSA
  2. 2.Social and Scientific Systems, Inc.Silver SpringUSA

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