title: Event-rate and delta inflation when evaluating mortality as a primary outcome from randomized controlled trials of nutritional interventions during critical illness: a systematic review.
abstract: BACKGROUND
  There is a lack of high-quality evidence that proves that nutritional interventions during critical illness reduce mortality.
  
  
  OBJECTIVE
  We evaluated whether power calculations for randomized controlled trials (RCTs) of nutritional interventions that used mortality as the primary outcome were realistic, and whether overestimation was systematic in the studies identified to determine whether this was due to overestimates of event rate or delta.
  
  
  METHODS
  A systematic review of the literature between 2005 and 2015 was performed to identify RCTs of nutritional interventions administered to critically ill adults that had mortality as the primary outcome. Predicted event rate (predicted mortality during the control), predicted mortality during intervention, predicted delta (predicted difference between mortality during the control and intervention), actual event rate (observed mortality during control), observed mortality during intervention, and actual delta (difference between observed mortality during the control and intervention) were recorded. The event-rate gap (predicted event rate minus observed event rate), the delta gap (predicted delta minus observed delta), and the predicted number needed to treat were calculated. Data are shown as median (range).
  
  
  RESULTS
  Fourteen articles were extracted, with power calculations provided for 10 studies. The predicted event rate was 29.9% (20.0–52.4%), and the predicted delta was 7.9% (3.0–20.0%). If the study hypothesis was proven correct then, on the basis of the power calculations, the number needed to treat would have been 12.7 (5.0–33.3) patients. The actual event rate was 25.3% (6.1–50.0%), the observed mortality during the intervention was 24.4% (6.3–39.7%), and the actual delta was 0.5% (−10.2–10.3%), such that the event-rate gap was 2.6% (−3.9–23.7%) and delta gap was 7.5% (3.2–25.2%).
  
  
  CONCLUSIONS
  Overestimates of delta occur frequently in RCTs of nutritional interventions in the critically ill that are powered to determine a mortality benefit. Delta inflation may explain the number of "negative" studies in this field of research.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Summers
authors.forename: Lee-anne S
authors.initials: LA
authors.lastname: Chapple
authors.forename: Stephen A
authors.initials: SA
authors.lastname: McClave
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
mesh_terms: D000328:Adult; D016638:Critical Illness / Q000401:mortality* / Q000628:therapy; D016208:Databases, Factual; D006801:Humans; D044623:Nutrition Therapy / Q000379:methods*; D009752:Nutritional Status; D016032:Randomized Controlled Trials as Topic