Placental Growth Factor (PlGF)- Based Biomarker Testing to Help Diagnose Pre-eclampsia in People With Suspected Pre-eclampsia: A Health Technology Assessment

Pre-eclampsia is a potentially serious condition affecting up to 5% of pregnancies, most frequently after 20 weeks' gestation. Placental growth factor (PlGF)-based tests measure either the blood level of PlGF or the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF. They are intended to complement standard clinical assessment to help diagnose pre-eclampsia in people with suspected pre-eclampsia. We conducted a health technology assessment of PlGF-based biomarker testing as an adjunct to standard clinical assessment to help diagnose pre-eclampsia in pregnant people with suspected pre-eclampsia, which included an evaluation of diagnostic accuracy, clinical utility, cost-effectiveness, the budget impact of publicly funding PlGF-based biomarker testing, and an assessment of preferences and values. We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using AMSTAR 2, Cochrane Risk of Bias tool, the Quality of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic literature search of the economic evidence. We did not conduct a primary economic evaluation as the impact of the test on maternal and neonatal outcomes is uncertain. We also analyzed the budget impact of publicly funding PlGF-based biomarker testing in pregnant people with suspected pre-eclampsia in Ontario. To contextualize the potential value of PlGF-based biomarker testing, we spoke with people whose pregnancies had been impacted by pre-eclampsia as well as their family members. We included one systematic review and one diagnostic accuracy study in the clinical evidence review. The Elecsys sFlt-1/PlGF ratio test using a test cut-off of less than 38 for ruling out pre-eclampsia within 1 week yielded a negative predictive value (NPV) of 99.2% and the DELFIA Xpress PlGF 1-2-3 test using a cut-off of 150 pg/mL or greater for ruling out pre-eclampsia within 1 week yielded a NPV of 94.8% (diagnostic GRADE: Moderate for both tests). All clinical utility outcomes were associated with uncertainties (GRADE: Low).We included 13 studies in the economic evidence review, most of which concluded that the use of PlGF-based biomarker testing resulted in cost savings. Seven studies were partially applicable to the Ontario health care setting but have some important li