When the results of a single study were reported in more than one publication, only the most recent and complete data were included in the meta-analysis. Studies were included in the analysis if (1) they were RCTs comparing any therapy with placebo, no treatment, or supportive care; (2) they included HCC patients with or without metastatic disease; (3) 1-year or 2-year survival was assessed as an outcome measure of the effect of the treatment; and (4) they had been published or accepted for publication as full-length articles. Among the 485 studies reviewed (Fig. 1), 30 RCTs8–37 met the inclusion criteria. Studies were excluded if they

did not have an adequate control arm; if they were nonrandomized or if they enrolled randomized and nonrandomized patients; and if they were published

Erlotinib manufacturer only in abstract form. Talazoparib in vivo The rationale for excluding studies published as abstracts only was that the methodological quality could not be assessed. The RCTs were reviewed using a list of predefined, pertinent questions that concerned the characteristics of patients, treatments, outcomes, and study validity. Each trial was evaluated and classified by three independent investigators (C.C., A.C., and G.C.). Discrepancies among reviewers were infrequent (overall interobserver variation of <10%) and were resolved by discussion. The methodological quality of the studies was assessed by five principal criteria (Supporting Table 1), using those established by Jadad et al.38 and Bañares et al.,39 as suggested by the Panel of Experts in HCC-Design Clinical Trials.4 The quality of trials was evaluated according to each separate component. The maximum possible score was 10 points. Pooled estimates of 1-year and 2-year survival rates were calculated using random-effects logistic regression analysis after applying sample weights according to the sample size. Heterogeneity among studies was assessed with the Pearson chi-squared test. Three different methods were used to explore and explain the diversity

among studies: (1) stratum analysis of variables suspected of having caused inconsistency, (2) medchemexpress meta-regression, and (3) subgroup analysis. Therefore, stratum-specific rates of the 1-year and 2-year survival rates for different patient-level and study-level covariates were calculated. We used 16 stratifying variables: publication year, study validity, study location, mean age, percentage of males, percentage of alcohol-related liver disease, percentage of hepatitis B virus (HBV)–related liver disease, percentage of hepatitis C virus (HCV)–related liver disease, percentage of performance status 0 subjects, mean serum albumin, mean total bilirubin, prothrombin activity, percentage of solitary tumors, percentage of portal thrombosis, percentage of Child-Pugh A patients, and percentage of Okuda stage I patients.