Three biomarker tests to help diagnose preterm labour: a systematic review and economic evaluation.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. STUDY REGISTRATION: The study is registered as PROSPERO CRD42017072696. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Infants may suffer from health problems if they are born early. If a mother has symptoms of labour before her baby is due, a test could be used to predict if the symptoms are real or a false alarm. A test could help the doctor to decide whether the mother needs treatment or to move to a specialist hospital or if she could be sent home (if it is a false alarm). Our report compares three tests [PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim^® Partus (Medix Biochemica, Espoo, Finland) and the Fetal Fibronectin (fFN) Test (Hologic, Inc., Marlborough, MA, USA)] on how well they predict an early birth and how the costs and the long-term health outcomes of the child compare between and among tests. All the published literature reporting the accuracy of the three tests and their costs was reviewed. We developed a new cost-effectiveness model, which estimated the long-term health outcomes of the child based on the test results. Twenty of the studies reviewed looked at how good the tests were at predicting an early birth within the next 7 days, and six looked at predicting birth within 48 hours. The designs of the studies and the women taking part in the studies varied greatly. This meant that comparing the accuracy of the tests was very difficult and it would be unfair to decide which test was the best. Our model suggested no firm conclusions for the cost-effectiveness of fFN compared with Actim Partus. PartoSure appears to be less costly than Actim Partus and equally good at predicting preterm birth, but this is based on a study of very few patients. There were no data that allowed us to compare all three tests together. The accuracy of the results is uncertain, mainly because all the studies are very different. We are aware of four related UK trials that are currently ongoing that plan to include large numbers of women.

Mutations in the hepatocyte nuclear factor-1ß (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations.

OBJECTIVE: Congenital uterine abnormalities are common and may be associated with developmental renal abnormalities. Mutations of the hepatocyte nuclear factor-1ß (HNF1B) gene are associated with renal and uterine abnormalities. We aimed to study the role of HNF1B mutations in a cohort with congenital uterine abnormalities. STUDY DESIGN: We tested 108 probands with uterine abnormalities for HNF1B mutations. We collected clinical information from patient records. RESULTS: Nine of 108 women (8%) had a mutation or deletion in the HNF1B gene. Abnormal HNF1B was found in 18% of the 50 probands who had both uterine and renal abnormalities but in none of the 58 women with isolated uterine abnormalities. CONCLUSION: Mutations of the HNF1B gene are found in women with both uterine and renal abnormalities but are rare in isolated uterine abnormalities. We suggest that HNF1B testing should be performed in patients with both renal and uterine abnormalities, but not in patients with isolated uterine abnormalities.

Group therapy for repeated deliberate self-harm in adolescents: failure of replication of a randomized trial.

OBJECTIVE: To replicate a study, which found group therapy superior to routine care in preventing the recurrence of self-harming behavior in adolescents who had deliberately harmed themselves on at least two occasions. METHOD: Single blind study with parallel randomized groups undertaken in three sites in Australia. The primary outcome measure was repetition of self-harm, assessed on average after 6 and 12 months. Secondary outcome measures included suicidal ideation, psychiatric disorder, and service use. RESULTS: Seventy-two adolescents aged 12 to 16 years (91% female subjects) were randomized to group therapy or routine care. Primary outcome data were available for 68 of the 72 randomized participants. More adolescents randomized to group therapy than those randomized to routine care had self-harmed by 6 months (30/34 versus 23/34, chi = 4.19, p =.04), and there was a statistically nonsignificant trend for this pattern to be repeated in the interval of 6 to 12 months (30/34 versus 24/34, chi = 3.24, p =.07). There were few differences between the treatment groups on secondary outcome measures, other than a trend for greater improvement over time on global symptom ratings among the experimental group compared with the control group. CONCLUSIONS: Our findings contradict those of the original study. Some differences in participant characteristics between the studies, along with less experience at the Australian sites in delivering the intervention, may have accounted for the different outcome. The benefit of group therapy for deliberate self-harm is unproven outside the environment in which it was originally developed.