Peninsula Technology Assessment Group (PenTAG), University of Exeter Medical School, University of Exeter, Exeter, UK.
Health Economics Group, University of Exeter Medical School, University of Exeter, Exeter, UK.
Health Technol Assess. 2019 Mar;23(13):1-226. doi: 10.3310/hta23130.
Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate) admissions into hospitals or transfers to specialist units.
The purpose of this report is to assess the test accuracy, clinical effectiveness and cost-effectiveness of the diagnostic tests PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim Partus (Medix Biochemica, Espoo, Finland) and the Rapid Fetal Fibronectin (fFN) 10Q Cassette Kit (Hologic, Inc., Marlborough, MA, USA) at thresholds ≠50 ng/ml [quantitative fFN (qfFN)] for women presenting with signs and symptoms of preterm labour relative to fFN at 50 ng/ml.
Systematic reviews of the published literature were conducted for diagnostic test accuracy (DTA) studies of PartoSure, Actim Partus and qfFN for predicting preterm birth, the clinical effectiveness following treatment decisions informed by test results and economic evaluations of the tests. A model-based economic evaluation was also conducted to extrapolate long-term outcomes from the results of the diagnostic tests. The model followed the structure of the model that informed the 2015 National Institute for Health and Care Excellence guidelines on preterm labour diagnosis and treatment, but with antenatal steroids use, as opposed to tocolysis, driving health outcomes.
Twenty studies were identified evaluating DTA against the reference standard of delivery within 7 days and seven studies were identified evaluating DTA against the reference standard of delivery within 48 hours. Two studies assessed two of the index tests within the same population. One study demonstrated that depending on the threshold used, qfFN was more or less accurate than Actim Partus, whereas the other indicated little difference between PartoSure and Actim Partus. No study assessing qfFN and PartoSure in the same population was identified. The test accuracy results from the other included studies revealed a high level of uncertainty, primarily attributable to substantial methodological, clinical and statistical heterogeneity between studies. No study compared all three tests simultaneously. No clinical effectiveness studies evaluating any of the three biomarker tests were identified. One partial economic evaluation was identified for predicting preterm birth. It assessed the number needed to treat to prevent a respiratory distress syndrome case with a 'treat-all' strategy, relative to testing with qualitative fFN. Because of the lack of data, our de novo model involved the assumption that management of pregnant women fully adhered to the results of the tests. In the base-case analysis for a woman at 30 weeks' gestation, Actim Partus had lower health-care costs and fewer quality-adjusted life-years (QALYs) than qfFN at 50 ng/ml, reducing costs at a rate of £56,030 per QALY lost compared with qfFN at 50 ng/ml. PartoSure is less costly than Actim Partus while being equally effective, but this is based on diagnostic accuracy data from a small study. Treatment with qfFN at 200 ng/ml and 500 ng/ml resulted in lower cost savings per QALY lost relative to fFN at 50 ng/ml than treatment with Actim Partus. In contrast, qfFN at 10 ng/ml increased QALYs, by 0.002, and had a cost per QALY gained of £140,267 relative to fFN at 50 ng/ml. Similar qualitative results were obtained for women presenting at different gestational ages.
There is a high degree of uncertainty surrounding the test accuracy and cost-effectiveness results. We are aware of four ongoing UK trials, two of which plan to enrol > 1000 participants. The results of these trials may significantly alter the findings presented here.
The study is registered as PROSPERO CRD42017072696.
The National Institute for Health Research Health Technology Assessment programme.
早产可能会导致儿童出现短期和长期的健康问题。准确诊断早产可以防止不必要的（或确保适当的）住院或转至专科病房。
本报告旨在评估 PartoSure™（Parsagen Diagnostics Inc.，马萨诸塞州波士顿）、Actim Partus（Medix Biochemica，芬兰埃斯波）和快速胎儿纤维连接蛋白（fFN）10Q 试剂盒（Hologic，马萨诸塞州马尔伯勒）在 ≠50ng/ml（定量 fFN（qfFN））阈值下对出现早产症状和体征的女性的诊断测试准确性、临床效果和成本效益，而 fFN 阈值为 50ng/ml。
对 PartoSure、Actim Partus 和 qfFN 预测早产的已发表文献进行了系统评价，评估了其预测早产的诊断测试准确性（DTA），评估了根据测试结果做出治疗决策的临床效果，并对测试进行了经济评价。还进行了基于模型的经济评估，从诊断测试的结果推断长期结果。该模型遵循了为早产诊断和治疗制定的 2015 年国家卫生与临床优化研究所指南的模型结构，但使用产前类固醇治疗，而不是使用保胎治疗，来驱动健康结果。
共确定了 20 项评估与 7 天内分娩的参考标准相对的 DTA 研究，以及 7 项评估与 48 小时内分娩的参考标准相对的 DTA 研究。两项研究在同一人群中评估了两项指标测试。一项研究表明，取决于使用的阈值，qfFN 的准确性高于或低于 Actim Partus，而另一项研究表明 PartoSure 和 Actim Partus 之间的差异很小。没有研究确定 qfFN 和 PartoSure 在同一人群中的准确性。其他纳入研究的测试准确性结果存在高度不确定性，主要归因于研究之间存在大量的方法学、临床和统计学异质性。没有研究同时比较所有三种测试。没有发现评估三种生物标志物测试的临床效果研究。有一项部分经济评估用于预测早产。它评估了使用定性 fFN 进行治疗的情况下，预防呼吸窘迫综合征病例所需的治疗人数。由于缺乏数据，我们的从头模型涉及到一个假设，即孕妇的管理完全遵循测试结果。在妊娠 30 周的女性的基础病例分析中，与 qfFN 50ng/ml 相比，Actim Partus 的医疗保健成本更低，质量调整生命年（QALY）更少，与 qfFN 50ng/ml 相比，每失去一个 QALY 可降低 56030 英镑的成本。PartoSure 的成本低于 Actim Partus，同时效果相当，但这是基于一项小型研究的诊断准确性数据。与 qfFN 50ng/ml 相比，qfFN 200ng/ml 和 500ng/ml 的治疗方案每失去一个 QALY 可节省的成本低于 Actim Partus。相比之下，qfFN 10ng/ml 增加了 0.002 的 QALY，与 qfFN 50ng/ml 相比，每获得一个 QALY 的成本为 140267 英镑。对于在不同孕龄出现的女性，也得到了类似的定性结果。
测试准确性和成本效益结果存在高度不确定性。我们知道有四项正在英国进行的试验，其中两项计划招募超过 1000 名参与者。这些试验的结果可能会显著改变这里提出的发现。
该研究在 PROSPERO CRD42017072696 注册。
英国国家卫生研究院卫生技术评估计划。
