title: Searching for indirect evidence and extending the network of studies for network meta-analysis: case study in venous thromboembolic events prevention following elective total knee replacement surgery.
abstract: OBJECTIVE
  To evaluate the effect of study identification methods and network size on the relative effectiveness and cost-effectiveness of recommended pharmacological venous thromboembolic events (VTEs) prophylaxis for adult patients undergoing elective total knee replacement surgery in the United Kingdom.
  
  
  METHODS
  A stepwise literature search specifically designed to identify indirect evidence was conducted to extend the original clinical review from the latest National Institute for Health and Care Excellence (NICE) VTE technology appraisal. Different network sizes or network orders, based on the successive searches, informed three network meta-analyses (NMAs), which were compared with a replicated base case. The resulting comparative estimates were inputted in an economic model to investigate the effect of network size on cost-effectiveness probabilities.
  
  
  RESULTS
  Searches increased the number of indirect comparisons between VTE interventions, progressively widening the relevant network of studies for NMA. Precision around mean relative treatment effects was increased as the network was extended from the base case to first-order NMA, but further extensions had limited effect. Cost-effectiveness analysis results were largely insensitive to variation in clinical inputs from the different NMA orders.
  
  
  CONCLUSIONS
  No standard methodology is currently recommended by NICE to identify the most relevant network of studies for NMA. Our study showed that optimizing the identification of studies for NMA can extend the evidence base for analysis and reduce the uncertainty in relative effectiveness estimates. Although in our example network extensions did not affect the acceptability of available treatments in VTE prevention based on cost-effectiveness results, it may in other applications.
authors: Department of Health Sciences, University of Leicester, Leicester, UK. Electronic address: pascale.dequen@le.ac.uk.
authors: Pascale
authors: P
authors: Dequen
authors: Department of Health Sciences, University of Leicester, Leicester, UK.
authors: Alex J
authors: AJ
authors: Sutton
authors: Oxford Outcomes Ltd., Oxford, UK.
authors: David A
authors: DA
authors: Scott
authors: Department of Health Sciences, University of Leicester, Leicester, UK.
authors: Keith R
authors: KR
authors: Abrams
mesh_terms: D000328:Adult; D019645:Arthroplasty, Replacement, Knee; D003362:Cost-Benefit Analysis; D019317:Evidence-Based Medicine; D006801:Humans; D018803:Models, Economic; D011183:Postoperative Complications / Q000191:economics* / Q000517:prevention & control*; D011720:Pyrazoles / Q000191:economics* / Q000627:therapeutic use*; D011728:Pyridones / Q000191:economics* / Q000627:therapeutic use*; D006113:United Kingdom; D054556:Venous Thromboembolism / Q000191:economics* / Q000517:prevention & control*
chemical_list: D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban
keywords: evidence synthesis; indirect treatment comparison; network meta-analysis; relative effectiveness; venous thromboembolism