The impact of global recruitment and country income on placebo rates in inflammatory bowel disease clinical trials.

Abstract

Introduction: Despite progress in understanding placebo effects in clinical trials of inflammatory bowel disease (IBD), there is a limited understanding of how socioeconomic factors of recruiting countries impact placebo rates. We investigated the association of socioeconomic factors across recruitment sites on placebo rates in IBD randomized controlled trials.

Methods: We examined the association of clinical and endoscopic remission and response to the weighted Gross National Index (GNI) per capita, Human Development Index (HDI), and out-of-pocket health expenditures as a percentage of current health expenditures (OOP_CHE) of identified trials using mixed effects linear regression.

Results: Across 76 trials (Crohn's disease [CD]: n = 32; ulcerative colitis [UC]: n = 44), placebo response rates over time were largely stable, with a small increase across time in clinical remission for CD trials (β = 0.4% per increase in study year, 95% CI: 0.3%-0.84%, P = .04) and a small decrease across time in endoscopic response for UC trials (β = -1.39% per increase in study year, 95% CI: -1.79, -0.99, P < .001). Clinical response was most susceptible to changes in socioeconomic factors in IBD trials (β = -2.96% per 10 000 USD increase in study GNI, 95% CI: -4.98, -0.95%, P = .004; P < .05 for HDI and OOP_CHE). Across both conditions, decreases in clinical response were associated with increases in HDI and OOP_CHE (CD HDI: β = -1.15% per 0.01 increase in study HDI, 95% CI: -2.24, -0.06%, P = .04; UC HDI: β = -0.66% per 0.01 increase in study HDI, 95% CI: -1.19, -0.12%, P = .02).

Discussion: We found that placebo clinical response was most susceptible to influences of site-level socioeconomic wellbeing. These findings highlight that estimation of placebo rates in trial planning should account for geographic location of recruiting sites.