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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

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Abstract

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.

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Abbreviations

BIW:

Every other week

CART:

Classification and tree

EOW:

Every other week

IGA:

Investigator global assessment

IM:

Intramuscularly

IV:

Intravenously

PASI:

Psoriasis Area Severity Index

PASI 75:

75 % improvement in Psoriasis Area Severity Index

PGA:

Physician global assessment

PsA:

Psoriatic arthritis

PsO:

Psoriasis

QIW:

Four times weekly

QW:

Every week

RCT:

Randomized controlled trial

SC:

Subcutaneously

TNF:

Tumor necrosis factor

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Acknowledgments

We thank Gloria Won at the Fishbon Library for her help with database searching.

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The authors declare that they have no conflict of interest.

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Correspondence to Howard I. Maibach.

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Lamel, S.A., Myer, K.A., Younes, N. et al. 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. Arch Dermatol Res 304, 707–717 (2012). https://doi.org/10.1007/s00403-012-1266-9

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