title: Age-standardisation when target setting and auditing performance of Down syndrome screening programmes.
abstract: OBJECTIVE
  To describe and illustrate a method of setting Down syndrome screening targets and auditing performance that allows for differences in the maternal age distribution.
  
  
  METHODS
  A reference population was determined from a Gaussian model of maternal age. Target detection and false-positive rates were determined by standard statistical modelling techniques, except that the reference population rather than an observed population was used. Second-trimester marker parameters were obtained for Down syndrome from a large meta-analysis, and for unaffected pregnancies from the combined results of more than 600,000 screens in five centres. Audited detection and false-positive rates were the weighted average of the rates in five broad age groups corrected for viability bias. Weights were based on the age distributions in the reference population.
  
  
  RESULTS
  Maternal age was found to approximate reasonably well to a Gaussian distribution with mean 27 years and standard deviation 5.5 years. Depending on marker combination, the target detection rates were 59 to 64% and false-positive rate 4.2 to 5.4% for a 1 in 250 term cut-off; 65 to 68% and 6.1 to 7.3% for 1 in 270 at mid-trimester. Among the five centres, the audited detection rate ranged from 7% below target to 10% above target, with audited false-positive rates better than the target by 0.3 to 1.5%.
  
  
  CONCLUSIONS
  Age-standardisation should help to improve screening quality by allowing for intrinsic differences between programmes, so that valid comparisons can be made.
authors.affiliation: Reproductive Epidemiology, University of Leeds, UK. h.s.cuckle@leeds.ac.uk
authors.forename: Howard
authors.initials: H
authors.lastname: Cuckle
authors.forename: David
authors.initials: D
authors.lastname: Aitken
authors.forename: Sandra
authors.initials: S
authors.lastname: Goodburn
authors.forename: Brian
authors.initials: B
authors.lastname: Senior
authors.forename: Kevin
authors.initials: K
authors.lastname: Spencer
authors.forename: Sue
authors.initials: S
authors.lastname: Standing
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D004739:England; D005260:Female; D006801:Humans; D008423:Maternal Age; D008485:Medical Audit; D015201:Meta-Analysis as Topic; D016011:Normal Distribution; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000592:standards*; D011785:Quality Assurance, Health Care