title: Penalized regression for interval-censored times of disease progression: Selection of HLA markers in psoriatic arthritis.
abstract: 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.
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
mesh_terms: D000465:Algorithms; D015535:Arthritis, Psoriatic / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D006680:HLA Antigens / Q000097:blood*; D006801:Humans; D015995:Prevalence; D012044:Regression Analysis; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006680:HLA Antigens
keywords: EM algorithm; Interval-censoring; LASSO; Penalized regression; SCAD; Variable selection