title: Statistical learning of origin-specific statically optimal individualized treatment rules.
abstract: Consider a longitudinal observational or controlled study in which one collects chronological data over time on a random sample of subjects. The time-dependent process one observes on each subject contains time-dependent covariates, time-dependent treatment actions, and an outcome process or single final outcome of interest. A statically optimal individualized treatment rule (as introduced in van der Laan et. al. (2005), Petersen et. al. (2007)) is a treatment rule which at any point in time conditions on a user-supplied subset of the past, computes the future static treatment regimen that maximizes a (conditional) mean future outcome of interest, and applies the first treatment action of the latter regimen. In particular, Petersen et. al. (2007) clarified that, in order to be statically optimal, an individualized treatment rule should not depend on the observed treatment mechanism. Petersen et. al. (2007) further developed estimators of statically optimal individualized treatment rules based on a past capturing all confounding of past treatment history on outcome. In practice, however, one typically wishes to find individualized treatment rules responding to a user-supplied subset of the complete observed history, which may not be sufficient to capture all confounding. The current article provides an important advance on Petersen et. al. (2007) by developing locally efficient double robust estimators of statically optimal individualized treatment rules responding to such a user-supplied subset of the past. However, failure to capture all confounding comes at a price; the static optimality of the resulting rules becomes origin-specific. We explain origin-specific static optimality, and discuss the practical importance of the proposed methodology. We further present the results of a data analysis in which we estimate a statically optimal rule for switching antiretroviral therapy among patients infected with resistant HIV virus.
authors.affiliation: Division of Biostatistics, School of Public Health, University of California, Berkeley, laan@stat.berkeley.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van der Laan
authors.forename: Maya L
authors.initials: ML
authors.lastname: Petersen
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D003198:Computer Simulation; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015233:Models, Statistical; D057285:Precision Medicine / Q000379:methods*; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral