Placental growth factor (PLGF)-based testing to help diagnose suspected pre-eclampsia: a systematic review and economic evaluation

Backgroun: predicting a diagnosis of pre-eclampsia is based on a combination of clinical assessment of blood pressure, presence of protein in the urine, symptoms, and laboratory test abnormalities. Accurately detecting pre-eclampsia is important to avoid false-positive diagnoses which could lead to unnecessary antenatal admissions and/or preterm delivery. Four blood tests that measure the biomarkers of placental growth factor (PLGF) or the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to PLGF, are available (known as Triage, Elecsys, DELFIA Xpress, and BRAHMS Kryptor tests). Abnormal measurements of these biomarkers can be used as an aid to predict a diagnosis of pre-eclampsia and maternal and fetal outcomes.<br/><br/>Objectives: to evaluate the test accuracy, clinical effectiveness and cost-effectiveness of PLGF-based tests used in conjunction with standard clinical assessment for predicting pre-eclampsia and maternal and fetal outcomes in pregnant women who are referred to secondary care with suspected pre-eclampsia in weeks 20–37 of pregnancy.<br/><br/>Data sources and methods: a systematic review of the diagnostic/prognostic accuracy and clinical effectiveness of PLGF-based tests with standard clinical assessment. Database included MEDLINE, Embase, and Cochrane Library,. Other sources searched included relevant conference proceedings and websites, grey literature and research in progress. The most recent date of searching was 18th March 2021. An independent economic analysis was conducted using a decision tree model. The model includes short term costs and quality-adjusted life years (QALYs) for the management of women, maternal and neonatal outcomes and long-term outcomes for severe neonatal complications. The model compared the use of the test alongside standard clinical assessment to standard clinical assessment only. Two different estimates of standard clinical assessment were included, from the INSPIRE study and from NICE Diagnostic Guidance 23.<br/><br/>Results: seventeen studies were included in the systematic review. Two large, randomised trials provided the best available evidence to inform the economic model - The PARROT trial (Triage test) and the INSPIRE trial (Elecsys test). When used as rule-out tests for pre-eclampsia (with neonatal outcomes included), all four tests produced higher QALYs and higher costs than both types of standard clinical assessment. The incremental cost per QALY ranged from £637 (DELFIA test vs standard clinical assessment from INSPIRE) to £47,393 (Triage test vs standard clinical assessment from DG23) per QALY. Incremental costs and QALYs were always very small, with incremental costs always less than the cost of the test and incremental QALYs always less than 0.006.<br/><br/>Limitations: although the evidence for PLGF-based tests is advancing there remains uncertainty for key, such as diagnostic sensitivity and specificity. This particularly affects the Elecsys test. <br/><br/>Conclusions: despite uncertainties from lack of data, and heterogeneity across studies, the use of PLGF-based tests to rule-out and rule-in pre-eclampsia has the potential to provide improved outcomes at reduced cost when compared with standard clinical assessment. <br/><br/>Future work: future research priorities include more rigorous evaluation of the DELFIA and BRAHMS PLGF-based tests, more evidence for Triage and Elecys as rule in tests, and greater focus on black, and Asian and mixed ethnicity groups.<br/>