title: The CALORIES trial: statistical analysis plan.
abstract: BACKGROUND
  The CALORIES trial is a pragmatic, open, multicentre, randomised controlled trial (RCT) of the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral route compared with early nutritional support via the enteral route in unplanned admissions to adult general critical care units (CCUs) in the United Kingdom. The trial derives from the need for a large, pragmatic RCT to determine the optimal route of delivery for early nutritional support in the critically ill.
  
  
  OBJECTIVE
  To describe the proposed statistical analyses for the evaluation of the clinical effectiveness in the CALORIES trial.
  
  
  METHODS
  With the primary and secondary outcomes defined precisely and the approach to safety monitoring and data collection summarised, the planned statistical analyses, including prespecified subgroups and secondary analyses, were developed and are described.
  
  
  RESULTS
  The primary outcome is all-cause mortality at 30 days. The primary analysis will be reported as a relative risk and absolute risk reduction and tested with the Fisher exact test. Prespecified subgroup analyses will be based on age, degree of malnutrition, acute severity of illness, mechanical ventilation at admission to the CCU, presence of cancer and time from CCU admission to commencement of early nutritional support. Secondary analyses include adjustment for baseline covariates.
  
  
  CONCLUSIONS
  In keeping with best trial practice, we have developed, described and published a statistical analysis plan for the CALORIES trial and are placing it in the public domain before inspecting data from the trial.
authors.affiliation: Intensive Care National Audit and Research Centre, London, United Kingdom. kathy.rowan@icnarc.org.
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Harvey
authors.affiliation: Intensive Care National Audit and Research Centre, London, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Parrott
authors.affiliation: Intensive Care National Audit and Research Centre, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Harrison
authors.affiliation: University College London Hospitals, National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Mythen
authors.affiliation: Intensive Care National Audit and Research Centre, London, United Kingdom.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rowan
mesh_terms: D003362:Cost-Benefit Analysis; D016638:Critical Illness / Q000453:epidemiology / Q000628:therapy*; D004750:Enteral Nutrition / Q000191:economics; D006801:Humans; D057194:Intention to Treat Analysis; D010288:Parenteral Nutrition / Q000191:economics; D016896:Treatment Outcome