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Activity Number: 148 - Statistical Methods, Challenges and Impacts on Early Phase Trials
Type: Invited
Date/Time: Monday, July 29, 2019 : 10:30 AM to 12:20 PM
Sponsor: ENAR
Abstract #300309 Presentation
Title: Advancing Pharmacogenomics Analysis of Drug Response in Early-Phase Clinical Trials
Author(s): Judong Shen and Hong Zhang* and Devan Mehrotra
Companies: Merck & Co., Inc. and Merck & Co., Inc. and Merck & Co., Inc
Keywords: Pharmacogenomics ; Drug response; CKAT ; Variant; Treatment; Biomarker

Pharmacogenomics (PGx) research holds the promise for detecting association between genetic variants and drug responses in early-phase clinical trials, but it is practically limited by small populations and thus low power to detect signals. It is critical to increase the power of PGx studies with small sample sizes so that the discoveries of variant-drug-response associations are not limited to common variants with large effect. In this talk, we first overview the challenges of PGx studies in early-phase trials and then introduce an adaptively weighted joint test (AWOT), which is an efficient and robust joint test of the single nucleotide polymorphism (SNP) main effect and SNP-treatment interaction effect for continuous and binary endpoints. An analytic procedure is proposed to accurately calculate the p-value. We evaluate AWOT through extensive simulation for different sample sizes and minor allele frequencies, etc. The result shows the proposed AWOT controls type I error well and outperforms existing methods across different signal patterns. We demonstrate the value of AWOT by applying it to PGx studies from the Merck early-phase trials.

Authors who are presenting talks have a * after their name.

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