title: Aggregate data meta-analysis with time-to-event outcomes.
abstract: In a meta-analysis of randomized controlled trials with time-to-event outcomes, an aggregate data approach may be required for some or all included studies. Variation in the reporting of survival analyses in journals suggests that no single method for extracting the log(hazard ratio) estimate will suffice. Methods are described which improve upon a previously proposed method for estimating the log(HR) from survival curves. These methods extend to life-tables. In the situation where the treatment effect varies over time and the trials in the meta-analysis have different lengths of follow-up, heterogeneity may be evident. In order to assess whether the hazard ratio changes with time, several tests are proposed and compared. A cohort study comparing life expectancy of males and females with cerebral palsy and a systematic review of five trials comparing two anti-epileptic drugs, carbamazepine and sodium valproate, are used for illustration.
authors.affiliation: Department of Mathematical Sciences, University of Liverpool, UK. prw@liv.ac.uk
authors.forename: Paula R
authors.initials: PR
authors.lastname: Williamson
authors.forename: Catrin Tudur
authors.initials: CT
authors.lastname: Smith
authors.forename: Jane L
authors.initials: JL
authors.lastname: Hutton
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D002220:Carbamazepine / Q000627:therapeutic use; D002547:Cerebral Palsy / Q000401:mortality; D015331:Cohort Studies; D004827:Epilepsy / Q000188:drug therapy / Q000517:prevention & control; D005260:Female; D006801:Humans; D015993:Life Tables; D008297:Male; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016019:Survival Analysis; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid