Wald N J, Bestwick J P, Huttly W J, Morris J K, George L M
Wolfson Institute of Preventive Medicine, Barts and the London Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
J Med Screen. 2006;13(4):166-71. doi: 10.1177/096914130601300402.
To validate empirically the accuracy of antenatal Down's syndrome screening using the Integrated test, to compare this with other screening tests (including the Integrated test with the addition of cross trimester [CT] marker ratios) and to suggest how such validation analyses should be presented and interpreted.
Using data from 7809 unaffected and 27 Down's syndrome pregnancies that had had an Integrated test, risk estimates for various screening tests (maternal age, Double, Triple, Quadruple, Combined, Integrated and serum Integrated tests) that use Integrated test markers were categorized according to quintile categories of risk estimates of the 27 affected pregnancies. For each screening test, the median risk estimate for each category was plotted against the observed prevalence within each category. Such validation plots were also produced for the Integrated test with CT marker ratios by measuring the level of the serum markers in the trimester of pregnancy not already measured in stored samples of all affected and a one-in-five sample of unaffected pregnancies. The robustness of the method was assessed by repeating the analysis for the Integrated test after re-classifying affected pregnancies with low risk estimates as unaffected, simulating the underascertainment of cases.
The validation plots (i) confirmed the accuracy of risk estimation for the different tests (by how close the points lay to the line of identity between predicted risk and observed prevalence), (ii) demonstrated the differences in screening performance of the different tests (by the range of risk spanned by the points and, in particular, the separation between the points representing the lowest risk and the next point), and (iii) are robust to underascertainment of affected pregnancies (by having little influence on the closeness of the points to the line of identity).
The validation plot is a useful, simple and robust way to assess the validity of new screening methods, to assess the accuracy of risk estimation and to audit the performance of screening programmes.
通过综合检测经验性地验证产前唐氏综合征筛查的准确性，将其与其他筛查检测（包括添加跨孕期[CT]标志物比率的综合检测）进行比较，并提出此类验证分析应如何呈现和解读。
利用7809例未受影响及27例唐氏综合征妊娠且已进行综合检测的数据，根据27例受影响妊娠风险估计的五分位数类别，对使用综合检测标志物的各种筛查检测（母亲年龄、二联检测、三联检测、四联检测、联合检测、综合检测及血清综合检测）的风险估计进行分类。对于每种筛查检测，将每个类别的中位风险估计值与该类别内观察到的患病率进行绘图。通过测量所有受影响妊娠及五分之一未受影响妊娠储存样本中尚未测量的孕期血清标志物水平，也为添加CT标志物比率的综合检测绘制了此类验证图。通过将低风险估计的受影响妊娠重新分类为未受影响妊娠后对综合检测重复进行分析，模拟病例漏诊情况，评估该方法的稳健性。
验证图（i）证实了不同检测风险估计的准确性（通过各点与预测风险和观察患病率之间的恒等线的接近程度），（ii）展示了不同检测筛查性能的差异（通过各点跨越的风险范围，特别是代表最低风险的点与下一个点之间的间距），并且（iii）对受影响妊娠的漏诊具有稳健性（通过对各点与恒等线的接近程度影响较小）。
验证图是评估新筛查方法有效性、评估风险估计准确性及审核筛查项目性能的一种有用、简单且稳健的方法。
