title: Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies.
abstract: OBJECTIVE
  To estimate the probabilistic cost-effectiveness of cascade screening methods in familial hypercholesterolaemia (FH) from the UK NHS perspective.
  
  
  METHODS
  Economic evaluation (cost utility analysis) comparing four cascade screening strategies for FH: Using low-density lipoprotein (LDL) cholesterol measurements to diagnose affected relatives (cholesterol method); cascading only in patients with a causative mutation identified and using DNA tests to diagnose relatives (DNA method); DNA testing combined with LDL-cholesterol testing in families with no mutation identified, only in patients with clinically defined 'definite' FH (DNA+DFH method); DNA testing combined with LDL-cholesterol testing in no-mutation families of both 'definite' and 'probable' FH patients (DNA+DFH+PFH). A probabilistic model was constructed to estimate the treatment benefit from statins, with all diagnosed individuals receiving high-intensity statin treatment.
  
  
  METHODS
  A cohort of 1000 people suspected of having FH aged 50 years for index cases and 30 years for relatives, followed for a lifetime.
  
  
  RESULTS
  Costs, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER).
  
  
  RESULTS
  The DNA+DFH+PFH method was the most cost-effective cascade screening strategy. The ICER was estimated at £3666/QALY. Using this strategy, of the tested relatives 30.6% will be true positives, 6.3% false positives, 61.9% true negatives and 1.1% false negatives. Probabilistic sensitivity analysis showed that this approach is 100% cost-effective using the conventional benchmark for cost-effective treatments in the NHS of between £20,000 and £30,000 per QALY gained.
  
  
  CONCLUSIONS
  Cascade testing of relatives of patients with DFH and PFH is cost-effective when using a combination of DNA testing for known family mutations and LDL-cholesterol levels in the remaining families. The approach is more cost-effective than current primary prevention screening strategies.
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medicine School, London WC1E 6JF, UK. rmhaseh@ucl.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Nherera
authors.forename: D
authors.initials: D
authors.lastname: Marks
authors.forename: R
authors.initials: R
authors.lastname: Minhas
authors.forename: M
authors.initials: M
authors.lastname: Thorogood
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000191:economics* / Q000209:etiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D005188:False Negative Reactions; D005189:False Positive Reactions; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000191:economics*; D017048:Health Care Costs; D040941:Heredity; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000191:economics / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000191:economics* / Q000235:genetics; D008390:Markov Chains; D008403:Mass Screening / Q000191:economics* / Q000379:methods*; D008875:Middle Aged; D018803:Models, Economic; D009154:Mutation; D010375:Pedigree; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D019057:Quality-Adjusted Life Years; D013222:State Medicine / Q000191:economics*; D013997:Time Factors; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors