Ication to AIDS study (ACTG175)We apply our approach to information from AIDS Clinical Trials Group Protocol 175 (ACTG175), which consists of 2139 HIV-infected subjects. In ACTG175, study subjects have been randomized to four distinct therapy groups: zidovudine (ZDV) monotherapy, ZDV+didanosine (ddI), ZDV+zalcitabine, and ddI monotherapy [22]. As in [23] and [24], we chose the CD4 countStat Approaches Med Res. Author manuscript; available in PMC 2013 May perhaps 23.Lu et al.Page(cells/mm3) at 20 5 weeks post-baseline because the key continuous response Y. In addition to the therapy indicator, we incorporated the identical 12 baseline covariates as deemed by [23] and [24] in our model, which consist of five continuous covariates: age (years), weight (kg), Karnofsky score (scale of 000), CD4 count (cells/mm3) at baseline and CD8 count (cells/ mm3) at baseline, and 7 binary covariates: hemophilia (0=no, 1=yes), homosexual activity (0=no, 1=yes), history of intravenous drug use (0=no, 1=yes), race (0=white, 1=non-white), gender (0=female, 1=male), antiretroviral history (0=naive, 1=experienced) and symptomatic status (0=asymptomatic, 1=symptomatic). The target of our study will be to discover the optimal treatment to maximize the expected CD4 count (cells/mm3) at 20 weeks postbaseline. We match model (two.1) with X becoming the 12 baseline covariates.Talazoparib For the remedy indicator A, we viewed as the following four analyses: Analysis 1: A = 0 for zidovudine (ZDV) monotherapy (532 subjects) vs. A = 1 for the other three treatment options combined collectively (1607 subjects). Right here Xi) “a 0.75. Analysis 2: Take into consideration the subset for sufferers getting the therapy ZDV +didanosine (ddI) or ZDV+zalcitabine. A = 0 for ZDV+zalcitabine (524 subjects) vs. A = 1 for ZDV+didanosine (ddI) (522 subjects). Right here Xi) “a 0.5. Evaluation three: Look at the subset for sufferers receiving the therapy ZDV +didanosine (ddI) or ddI monotherapy.Zidovudine A = 0 for ddI monotherapy (561 subjects) vs.PMID:23329650 A = 1 for ZDV+didanosine (ddI) (522 subjects). Here Xi) “a 0.five. Analysis 4: Consider the subset for patients receiving the treatment ZDV +zalcitabine or ddI monotherapy. A = 0 for ddI monotherapy (561 subjects) vs. A = 1 for ZDV+zalcitabine (524 subjects). Here Xi) “a 0.5.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn our analysis, we assumed the linear model for h(x; . For evaluation 1, the adaptive = LASSO estimator (48.46, 0, 0)T, implying that the other 3 remedies are uniformly greater than zidovudine (ZDV) monotherapy and all of the individuals really should be assigned towards the other 3 therapies. For analysis 2, except for the intercept, the new estimator also selects two significant covariates: age and homosexual activity (homo), and their corresponding estimates are -44.92, two.52, and -21.31, respectively. Consequently, the optimal therapy rule is I(-44.92 + two.52 * age – 21.31 * homo 0) for comparing treatments ZDV+didanosine (ddI) (A = 1) and remedy ZDV+zalcitabine (A = 0), or equivalently, to get a patient with homo = 0, assign to therapy 1 if age 17.eight and remedy 0 otherwise; although to get a patient with homo = 1, assign to therapy 1 if age 26.three and treatment 0 otherwise. Note that the age of study subjects ranges from 12 to 70. In accordance with the obtained optimal treatment rule, 978 out of 1046 patients (93.5 ) in this subset ought to be assigned to therapy ZDV+didanosine (ddI). It is also noted that therapy ZDV +zalcitabine is far more favorable to young individuals with AIDS. For evaluation 3, except for the intercept, t.