5 years. Patients in whom HCV RNA was undetectable at week 20 were categorized as responders and continued full-dose combination therapy for up to 48 weeks. Initial responders
were eligible for randomization into the trial if virologic breakthrough occurred during extended therapy or relapse followed 48 weeks of therapy. In addition, patients who were treated with peginterferon and ribavirin outside the lead-in phase of the HALT-C Trial were also eligible for randomization (“express” group) if they met criteria for nonresponse, breakthrough, or relapse. This approach to enrollment ensured that all patients had received optimal therapy with peginterferon and ribavirin8, 9 before they were enrolled into this long-term EGFR inhibitor trial, during which they might not be treated.5 After randomization, patients in both groups were seen at 3-month intervals for 3.5 years, at which point peginterferon was discontinued in the treatment group.
Nine patients assigned to the control group were treated “off-protocol” by nonstudy physicians, but they were included as controls in Palbociclib chemical structure our intention-to-treat analysis. Thereafter, all patients remained untreated and were seen at 6-month intervals. At each visit the occurrence of clinical outcomes (which had been established prospectively) was noted, including clinical events and laboratory markers of hepatic decompensation, HCC, or death. Although not a primary clinical outcome in the
HALT-C Trial, liver transplantation was included in this mortality analysis because these patients were likely to have died in the absence of liver transplantation. Most deaths were identified by study coordinators interacting with family members by way of telephone. In addition, periodic on-line searches were performed of the U.S. Social Security Death Index (SSDI) (http://ssdi.rootsweb.com/), which is generated from the U.S. Social Security Administration’s Death Master File. The SSDI was queried for any participant with whom the study site had no contact for at least 6 months. The last search of the SSDI was conducted in October, 2009. To account for the potential lag between date of death and 上海皓元 report to the SSDI, we included in our analysis deaths occurring on or before December 31, 2008. All deaths were reviewed by a seven-person, central review committee consisting of HALT-C Trial investigators blinded to the identity of the subject, study site, fibrosis versus cirrhosis stratum, but not randomization allocation (treatment or control), this information being required to assess treatment relatedness. The committee classified the primary cause of death into one of 15 categories (Supporting Table 1).