title: Economic Evaluations Alongside Efficient Study Designs Using Large Observational Datasets: the PLEASANT Trial Case Study.
abstract: BACKGROUND
  Large observational datasets such as Clinical Practice Research Datalink (CPRD) provide opportunities to conduct clinical studies and economic evaluations with efficient designs.
  
  
  OBJECTIVE
  Our objectives were to report the economic evaluation methodology for a cluster randomised controlled trial (RCT) of a UK NHS-delivered public health intervention for children with asthma that was evaluated using CPRD and describe the impact of this methodology on results.
  
  
  METHODS
  CPRD identified eligible patients using predefined asthma diagnostic codes and captured 1-year pre- and post-intervention healthcare contacts (August 2012 to July 2014). Quality-adjusted life-years (QALYs) 4 months post-intervention were estimated by assigning utility values to exacerbation-related contacts; a systematic review identified these utility values because preference-based outcome measures were not collected. Bootstrapped costs were evaluated 12 months post-intervention, both with 1-year regression-based baseline adjustment (BA) and without BA (observed).
  
  
  RESULTS
  Of 12,179 patients recruited, 8190 (intervention 3641; control 4549) were evaluated in the primary analysis, which included patients who received the protocol-defined intervention and for whom CPRD data were available. The intervention's per-patient incremental QALY loss was 0.00017 (bias-corrected and accelerated 95% confidence intervals [BCa 95% CI] -0.00051 to 0.00018) and cost savings were £14.74 (observed; BCa 95% CI -75.86 to 45.19) or £36.07 (BA; BCa 95% CI -77.11 to 9.67), respectively. The probability of cost savings was much higher when accounting for BA versus observed costs due to baseline cost differences between trial arms (96.3 vs. 67.3%, respectively).
  
  
  CONCLUSIONS
  Economic evaluations using data from a large observational database without any primary data collection is feasible, informative and potentially efficient. Clinical Trials Registration Number: ISRCTN03000938.
authors.affiliation: Health Economics and Decision Science (HEDS), ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK. matt.franklin@sheffield.ac.uk.
authors.forename: Matthew
authors.identifier: http://orcid.org/0000-0002-2774-9439
authors.initials: M
authors.lastname: Franklin
authors.affiliation: Health Economics and Decision Science (HEDS), ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Davis
authors.affiliation: Design, Trials & Statistics (DTS), ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Horspool
authors.affiliation: Health Economics and Decision Science (HEDS), ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Wei Sun
authors.initials: WS
authors.lastname: Kua
authors.affiliation: Design, Trials & Statistics (DTS), ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Julious
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics; D002648:Child; D002675:Child, Preschool; D017046:Cost Savings; D016208:Databases, Factual / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D011336:Probability; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012107:Research Design; D006113:United Kingdom