title: Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients.
abstract: BACKGROUND
  A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed.
  
  
  METHODS
  A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT.
  
  
  RESULTS
  If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million.
  
  
  CONCLUSIONS
  If future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as 'further research is needed' are replaced with 'further research is cost-effective and 'further funding of a trial is justified'.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01141894.
authors.affiliation: Karolinska Institute, CLINTEC, Division of Anaesthesiology and Department of Anaesthesia and Intensive Medicine, Karolinska University Hospital, Stockholm, Sweden. erzsebet.bartha@karolinska.se
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Bartha
authors.forename: Thomas
authors.initials: T
authors.lastname: Davidson
authors.forename: Thor-Henrik
authors.initials: TH
authors.lastname: Brodtkorb
authors.forename: Per
authors.initials: P
authors.lastname: Carlsson
authors.forename: Sigridur
authors.initials: S
authors.lastname: Kalman
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D003362:Cost-Benefit Analysis; D003627:Data Interpretation, Statistical; D003661:Decision Support Techniques; D003663:Decision Trees; D004280:Dobutamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D016527:Drug Costs; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000191:economics / Q000401:mortality; D005592:Fracture Fixation / Q000009:adverse effects* / Q000191:economics / Q000401:mortality; D006439:Hemodynamics / Q000187:drug effects*; D006620:Hip Fractures / Q000175:diagnosis / Q000191:economics / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D017721:Hospital Costs; D006801:Humans; D008297:Male; D008390:Markov Chains; D011183:Postoperative Complications / Q000191:economics / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D011336:Probability; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D035501:Uncertainty
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D004280:Dobutamine