title: Cost-effectiveness and diagnostic effectiveness analyses of multiple algorithms for the diagnosis of Lynch syndrome.
abstract: OBJECTIVE
  The optimal algorithm to identify Lynch syndrome (LS) among patients with colorectal cancer (CRC) is unclear. The definitive test for LS, germline testing, is too expensive to be applied in all cases. Initial screening with the revised Bethesda Guidelines (RBG) cannot be applied in a considerable number of cases due to missing information.
  
  
  METHODS
  We developed a model to evaluate the cost-effectiveness of 10 strategies for diagnosing LS. Three main issues are addressed: modeling estimates (20-40%) of RBG applicability; comparing sequential or parallel use of microsatellite instability (MSI) and immunohistochemistry (IHC); and a threshold analysis of the charge value below which universal germline testing becomes the most cost-effective strategy.
  
  
  RESULTS
  LS detection rates in RBG-based strategies decreased to 64.1-70.6% with 20% inapplicable RBG. The strategy that uses MSI alone had lower yield, but also lower cost than strategies that use MSI sequentially or in parallel with IHC. The use of MSI and IHC in parallel was less affected by variations in the sensitivity and specificity of these tests. Universal germline testing had the highest yield and the highest cost of all strategies. The model estimated that if charges for germline testing drop to $633-1,518, universal testing of all newly diagnosed CRC cases becomes the most cost-effective strategy.
  
  
  CONCLUSIONS
  The low applicability of RBG makes strategies employing initial laboratory-based testing more cost-effective. Of these strategies, parallel testing with MSI and IHC offers the most robust yield. With a considerable drop in cost, universal germline testing may become the most cost-effective strategy for the diagnosis of LS.
authors: Sections of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA, mgould@bcm.edu.
authors: Milena
authors: M
authors: Gould-Suarez
authors: Hashem B
authors: HB
authors: El-Serag
authors: Benjamin
authors: B
authors: Musher
authors: Luis Miguel
authors: LM
authors: Franco
authors: Guoqing J
authors: GJ
authors: Chen
mesh_terms: D000465:Algorithms; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000191:economics; D003362:Cost-Benefit Analysis / Q000379:methods*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000191:economics* / Q000706:statistics & numerical data; D006801:Humans; D008403:Mass Screening / Q000191:economics* / Q000706:statistics & numerical data