Global Recruiting Patterns and Placebo Response Rates in Clinical Trials of Psoriatic Arthritis and Plaque Psoriasis

Abstract

OBJECTIVE: Placebo effects are a significant challenge in the conduct of clinical trials. We explored how global recruitment patterns influence the extent of placebo responses in randomized controlled trials of psoriatic arthritis and plaque psoriasis. METHODS: We conducted an analysis of 51 trials (6,843 patients; 52% ± 5.7% female) in psoriatic arthritis and 43 trials (5,671 patients; 32% ± 7.1% female) in plaque psoriasis investigating biologic and targeted synthetic therapeutics. We investigated to what extent global recruitment patterns are related to the extent of response rates in the placebo arms of these clinical trials by investigating underlying socioeconomic factors using the average per capita gross national income (GNI; weighted for recruiting study centers per country) as proxy of these patterns in linear mixed models. RESULTS: We identified a negative association of GNI and placebo response rates on the primary endpoints across psoriatic arthritis trials (American College of Rheumatology 20%: β = -5.7% per 10,000 international dollars; 95% confidence interval [CI] -7.8% to -3.5%; P < 0.001) and plaque psoriasis trials (Psoriasis Area and Severity Index 75%: β = -1.1%; 95% CI -2.0 to -0.3; P = 0.011). Sensitivity analyses using other outcome measures and alternative economic metrics, such as the United Nations Human Development Index and World Health Organization out-of-pocket health expenditures, were confirmatory. CONCLUSION: The global expansion of trial recruitment to less affluent countries may increase placebo rates in studies of psoriatic arthritis and plaque psoriasis. These higher placebo rates may reflect the higher perceived benefit in these countries, leading to regression to the mean after patients have been successfully enrolled.

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