Cuckle 1999a.

Clinical features and settings	High‐risk referral for invasive testing and routine screening.
Participants	6730 participants. USA, UK and other European countries –multicentre study. Dates not reported. Pregnant women. 14‐19 weeks' gestation.
Study design	Prospective cohort study.
Target condition and reference standard(s)	Down's syndrome: 39 cases. Reference standard: amniocentesis, CVS or postnatal examination.
Index and comparator tests	Maternal urine beta core hCG (Chiron manual assay).
Follow‐up	Methods of follow‐up not reported.
Aim of study	A prospective evaluation of urine beta core hCG for Down's syndrome.
Notes
Table of Methodological Quality
Item	Authors' judgement	Description
Representative spectrum? All tests	Yes	Selective testing of high‐risk women as done in practice.
Acceptable reference standard? All tests	Yes	Karyotyping or follow‐up to birth.
Partial verification avoided? All tests	Unclear	Unclear if all women received a reference standard.
Differential verification avoided? All tests	No	Women had different reference standards.
Incorporation avoided? All tests	Yes	Index tests did not form part of the reference standard.
Reference standard results blinded? All tests	No	Reference standard interpreted with knowledge of index test results.
Index test results blinded? All tests	Yes	Index test conducted without knowledge of the reference standard.
Relevant clinical information? All tests	Yes	Information available as would be in standard clinical practice.
Uninterpretable results reported? All tests	No	No details given for test failures/uninterpretable measurements.
Withdrawals explained? All tests	No	No details of withdrawals given.