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Abstract：
OBJECTIVE: Several countries have included medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in their newborn screening programs. However, the sensitivity of the programs cannot be estimated directly as only individuals with a positive result undergo a definitive diagnostic test. We propose a framework to overcome this limitation and estimate the prevalence of disease, sensitivity of screening, and its yield relative to no screening.
METHODS: A Bayesian model simultaneously combined available prevalence data on the most common mutation of MCADD (c.985A>G) in screened and nonscreened populations using the relationship between true and apparent prevalence of disease. Data originated from screening pilots in England, disease surveillance studies, and published literature. Model validity and consistency were formally checked.
RESULTS: True prevalence of c.985A>G homozygotes in England was 6.2 per 100,000 individuals, and the sensitivity of the screening program was 94% (95% confidence interval [CI]: 74, 100%) compared with a detection rate in nonscreened areas of 48% (95% CI: 30, 68%) by age of 5 years. Hence, the screening program detected 47% (95% CI: 30, 60%) additional cases compared with no screening.
CONCLUSIONS: The sensitivity of the screening program in England was high and our estimation approach could be adapted to inform other jurisdictions, rare diseases, and newborn screening programs.
METHODS: A Bayesian model simultaneously combined available prevalence data on the most common mutation of MCADD (c.985A>G) in screened and nonscreened populations using the relationship between true and apparent prevalence of disease. Data originated from screening pilots in England, disease surveillance studies, and published literature. Model validity and consistency were formally checked.
RESULTS: True prevalence of c.985A>G homozygotes in England was 6.2 per 100,000 individuals, and the sensitivity of the screening program was 94% (95% confidence interval [CI]: 74, 100%) compared with a detection rate in nonscreened areas of 48% (95% CI: 30, 68%) by age of 5 years. Hence, the screening program detected 47% (95% CI: 30, 60%) additional cases compared with no screening.
CONCLUSIONS: The sensitivity of the screening program in England was high and our estimation approach could be adapted to inform other jurisdictions, rare diseases, and newborn screening programs.
摘要：
目的：一些国家已经将中链酰基辅酶A脱氢酶缺乏症（MCADD）纳入新生儿筛查计划。然而,程序的敏感性无法直接估计，因为只有阳性结果的个体才能接受明确的诊断测试。我们提出了一个框架来克服这一限制并估计疾病的患病率，筛查的敏感性，和它的产量相对于没有筛选。
方法：贝叶斯模型同时结合了筛查和非筛查人群中MCADD最常见突变（c.985A>G）的现有患病率数据，使用疾病真实和表观患病率之间的关系。数据来自英格兰的筛查飞行员，疾病监测研究,出版文献。对模型的有效性和一致性进行了形式化检验。
结果：英格兰c.985A>G纯合子的实际患病率为每100,000个人6.2，筛查方案的敏感性为94%(95%置信区间[CI]:74,100%),而非筛查区域的检出率为48%(95%CI:30,68%)。因此，与未筛查相比,筛查计划检测到47%(95%CI:30,60%)的额外病例.
结论：英格兰的筛查计划的敏感性很高，我们的评估方法可以适应其他司法管辖区，罕见疾病,和新生儿筛查计划。
方法：贝叶斯模型同时结合了筛查和非筛查人群中MCADD最常见突变（c.985A>G）的现有患病率数据，使用疾病真实和表观患病率之间的关系。数据来自英格兰的筛查飞行员，疾病监测研究,出版文献。对模型的有效性和一致性进行了形式化检验。
结果：英格兰c.985A>G纯合子的实际患病率为每100,000个人6.2，筛查方案的敏感性为94%(95%置信区间[CI]:74,100%),而非筛查区域的检出率为48%(95%CI:30,68%)。因此，与未筛查相比,筛查计划检测到47%(95%CI:30,60%)的额外病例.
结论：英格兰的筛查计划的敏感性很高，我们的评估方法可以适应其他司法管辖区，罕见疾病,和新生儿筛查计划。
