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

Abstract

Background: 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.

Methods: 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.

Results: 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 limitations; the remaining 6 studies were not applicable. We estimated that publicly funding PlGF-based biomarker testing for people with suspected pre-eclampsia in Ontario would lead to an additional annual cost of $0.27 million in year 1 to $0.46 million in year 5, for a total additional cost of $1.83 million over 5 years.Direct engagement included 24 people who had been impacted by pre-eclampsia during their pregnancies as well as one family member. Participants described the emotional and physical impacts of having suspected pre-eclampsia and subsequent treatments. Those that we spoke with valued shared decision-making and identified potential gaps in patient education, specifically as it relates to symptom management for suspected pre-eclampsia. Overall, the participants viewed PlGF-based biomarker testing positively for its perceived medical benefits and minimal invasiveness. They felt that access to PlGF-based biomarker testing may also improve health outcomes through improved patient education, care coordination, and patient-centred care (e.g., prompting more frequent prenatal monitoring, when needed). In addition, PlGF-based biomarker testing was perceived to be equally beneficial for family members who may act as the health care proxy in an emergency. Lastly, participants emphasized that there should be equitable access to PlGF-based biomarker testing and support from a care provider should be offered when trying to interpret the results, particularly if the results are accessible through an online patient portal.

Conclusions: Compared with standard clinical assessment alone in people with suspected pre-eclampsia (gestational age between 20 and 36 weeks + 6 days), PlGF-based biomarker testing as an adjunct to standard clinical assessment likely improves prediction of pre-eclampsia. It may also reduce time to pre-eclampsia diagnosis, severe adverse maternal outcomes, and length of stay in the neonatal intensive care unit, although the evidence is uncertain. PlGF-based biomarker testing may result in little to no difference in other clinical outcomes such as maternal admission to hospital and perinatal adverse outcomes.The economic literature review showed that PlGF-based biomarker testing was cost-effective for use in people with suspected pre-eclampsia, but with some uncertainties. A primary economic evaluation was not done for this health technology assessment because the impact of the test on maternal and neonatal outcomes is uncertain. Publicly funding PlGF-based biomarker testing for people with suspected pre-eclampsia would lead to an additional cost of $1.83 million over 5 years.Publicly funding PlGF-based biomarker testing was viewed favourably by people directly impacted by pre-eclampsia as well as their family members. Those with whom we spoke valued testing to help diagnose suspected pre-eclampsia and valued the potential medical benefits. Participants emphasized that patient education, and equitable access to PlGF-based biomarker testing should be requirements for implementation in Ontario.