title: Development of a composite endpoint for randomized controlled trials in liver surgery.
abstract: BACKGROUND
  The feasibility of randomized controlled trials (RCTs) in liver surgery using a single-component clinical endpoint is low as such endpoints require large sample sizes owing to their low incidence. A liver surgery-specific composite endpoint (CEP) could solve this problem. The aim of this study was to develop a liver surgery-specific CEP with well-defined components.
  
  
  METHODS
  Components of a liver surgery-specific CEP were selected based on a systematic literature search and consensus among 28 international hepatopancreatobiliary (HPB) surgeons. As an example, two prospective cohorts of patients who had undergone liver surgery in high-volume HPB centres were used to assess the event rate and effect of implementing a liver surgery-specific CEP.
  
  
  RESULTS
  Components selected for the liver surgery-specific CEP were ascites, postresectional liver failure, bile leakage, intra-abdominal haemorrhage, intra-abdominal abscess and operative mortality, all with a Clavien-Dindo grade of at least 3 and occurring within 90 days after initial surgery. The incidence of this liver surgery-specific CEP was 19.2 per cent in one cohort and 10.7 per cent in the other. These rates led to an approximately twofold reduction in the theoretical sample size required for an adequately powered RCT in liver surgery using the CEP as primary endpoint.
  
  
  CONCLUSIONS
  The proposed liver surgery-specific CEP consists of ascites, postresectional liver failure, bile leakage, intra-abdominal haemorrhage, intra-abdominal abscess and operative mortality. It has a considerably higher event rate than any of its components. Its use as the primary endpoint will increase the feasibility and comparability of RCTs in liver surgery.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands.
authors.forename: M A J
authors.initials: MA
authors.lastname: van den Broek
authors.forename: R M
authors.initials: RM
authors.lastname: van Dam
authors.forename: G J P
authors.initials: GJ
authors.lastname: van Breukelen
authors.forename: M H
authors.initials: MH
authors.lastname: Bemelmans
authors.forename: E
authors.initials: E
authors.lastname: Oussoultzoglou
authors.forename: P
authors.initials: P
authors.lastname: Pessaux
authors.forename: C H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: N
authors.initials: N
authors.lastname: Freemantle
authors.forename: S W M
authors.initials: SW
authors.lastname: Olde Damink
mesh_terms: D000368:Aged; D032921:Consensus; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis; D016032:Randomized Controlled Trials as Topic