Penalized regression for interval-censored times of disease progression: Selection of HLA markers in psoriatic arthritis

• Published in: Biometrics Vol. 71; no. 3; pp. 782 - 791
• Main Authors: Wu, Ying, Cook, Richard J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2015; International Biometric Society
• Subjects: Algorithms; Antigens; Arthritis; Arthritis, Psoriatic - blood; Arthritis, Psoriatic - diagnosis; Arthritis, Psoriatic - epidemiology; biomarkers; Biomarkers - blood; BIOMETRIC PRACTICE; Biometrics; biometry; clinical examination; clinical trials; cohort studies; disease course; Disease Progression; EM algorithm; hematologic tests; HLA antigens; HLA Antigens - blood; Humans; image analysis; Interval-censoring; LASSO; Leukocytes; patients; Penalized regression; Prevalence; Psoriasis; Regression Analysis; Reproducibility of Results; Risk Assessment - methods; SCAD; Sensitivity and Specificity; Severity of Illness Index; Time Factors; Variable selection; Penalized regression; SCAD; EM algorithm; Interval-censoring; LASSO; Variable selection
• ISSN: 0006-341X; 1541-0420; 1541-0420
• DOI: 10.1111/biom.12302

Times of disease progression are interval-censored when progression status is only known at a series of assessment times. This situation arises routinely in clinical trials and cohort studies when events of interest are only detectable upon imaging, based on blood tests, or upon careful clinical examination. We consider the problem of selecting important prognostic biomarkers from a large set of candidates when disease progression status is only known at irregularly spaced and individual-specific assessment times. Penalized regression techniques (e.g., LASSO, adaptive LASSO, and SCAD) are adapted to handle interval-censored time of disease progression. An expectation–maximization algorithm is described which is empirically shown to perform well. Application to the motivating study of the development of arthritis mutilans in patients with psoriatic arthritis is given and several important human leukocyte antigen (HLA) variables are identified for further investigation.