PGx7558: An Exploratory Study of Genetic Effects on Anoro (GSK573719/GW642444) in Chronic Obstructive Pulmonary Disease in Multiple Clinical Studies

Trial description: The primary objective of this study is to identify genetic variants associated with umeclidinium bromide/vilanterol, umeclidinium bromide, or vilanterol efficacy. A secondary objective is to identify genetic associations with baseline reversibility status and assess the effects of these genes on drug response.Genetic markers that have previously been associated with chronic obstructive pulmonary disease or a related phenotype or HLA genes will be prioritized into separate marker tiers and tested for association. All other common GWAS markers, measured or imputed, will be explored for association with the primary, secondary or tertiary outcome measures.The effects of covariates will be regressed out within each study group and each drug to get residuals followed by inverse normal transformation. For the primary analysis, the inverse normal transformed residuals will be pooled across study groups and across drugs to estimate genetic effects in patients treated with each drug-containing regimen. Three models will be investigated. The primary model will consider all potential covariates. In the second model, all potential covariates except reversibility related covariates will be considered. In the third model, only basic covariates will be considered by excluding reversibility and baseline disease characteristics. For analysis within each marker tier, the family wise error rate will be controlled to 5%. ANORO is a registered trademark of the GlaxoSmithKline group of companies.