Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases
by Honghui Zhou, Diane R. Mould
6Utility of Joint Population Exposure–Response Modeling Approach to Assess Multiple Continuous and Categorical Endpoints in Immunology Drug Development
Chuanpu Hu and Honghui Zhou
Janssen Research and Development, LLC, Global Clinical Pharmacology, 1400 McKean Road, Spring House, PA, 19477, USA
6.1 Introduction
Exposure–response (E–R) modeling of clinical endpoints is important for drug development by facilitating informative dose regimen selection. A widely used class of E–R models includes the Types I–IV indirect response (IDR) models [1]. These models are most often used to describe continuous physiological endpoints and their presumed consistency with the mechanism of drug action lends confidence to the model predictions. However, clinical trial endpoints are often disease scores that are not physiological variables. For example, two types of commonly used efficacy endpoints in rheumatoid arthritis (RA) are the 28‐joint disease activity score using CRP (DAS28) and 20%, 50%, and 70% improvement in the American College of Rheumatology disease severity criteria (ACR20, ACR50, and ACR70) [2]. In psoriatic arthritis (PsA), the Psoriasis Area and Severity Index (PASI) score, ranged 0–72 with 0.1 increments, is used in addition to the ACR criteria (for arthritis component) to measure the severity of the psoriatic component of the disease. Applications of IDR models to categorical clinical endpoints have emerged in the last decade via the latent variable approach [3].
Clinical trials ...