title: Latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint.
abstract: Informative exposure-response modeling of clinical endpoints is important in drug development. There has been much recent progress in latent variable modeling of ordered categorical endpoints, including the application of indirect response (IDR) models and accounting for residual correlations between multiple categorical endpoints. This manuscript describes a framework of latent-variable-based IDR models that facilitate easy simultaneous modeling of a continuous and a categorical clinical endpoint. The model was applied to data from two phase III clinical trials of subcutaneously administered ustekinumab for the treatment of psoriatic arthritis, where Psoriasis Area and Severity Index scores and 20, 50, and 70 % improvement in the American College of Rheumatology response criteria were used as efficacy endpoints. Visual predictive check and external validation showed reasonable parameter estimation precision and model performance.
authors.affiliation: Pharmacokinetics and Pharmacometrics, Biologics Clinical Pharmacology, Janssen Research and Development, LLC, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA, CHu25@its.jnj.com.
authors.forename: Chuanpu
authors.initials: C
authors.lastname: Hu
authors.forename: Philippe O
authors.initials: PO
authors.lastname: Szapary
authors.forename: Alan M
authors.initials: AM
authors.lastname: Mendelsohn
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D017326:Clinical Trials, Phase III as Topic; D023381:Endpoint Determination / Q000706:statistics & numerical data*; D006801:Humans; D007279:Injections, Subcutaneous; D008727:Methotrexate / Q000627:therapeutic use; D015233:Models, Statistical; D015337:Multicenter Studies as Topic; D011565:Psoriasis / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069549:Ustekinumab; D008727:Methotrexate