Original Title: Determinación de Biomarcadores de Preeclampsia sFlt-1 y PlGF

Authors' objectives: The aims of this report were: - To assess the diagnostic and prognostic accuracy of the sFlt-1/PlGF ratio for evaluating pregnant women with signs and/or symptoms suggestive of PE or with risk factors for PE. - To identify the most efficient cut-off values for sFlt-1/PlGF measurements for classifying (diagnosis rule in / rule out) pregnant women with signs and/or symptoms suggestive of PE or with risk factors for PE to allow decision-making based on the best scientific evidence. - To analyse studies evaluating the economic impact on the Spanish National Health System of introducing the sFlt-1/PlGF ratio into clinical practice for the management of patients with signs and/or symptoms suggestive of PE or with risk factors for PE.

Authors' results and conclusions: 1. The studies identified are clinically and methodologically heterogeneous, thus limiting extrapolation of the results to our setting. Moreover, the used terminology tends to confuse the concepts of prediction, diagnosis and prognosis. 2. In general, the designs and accuracy outcomes used in these studies present serious limitations for establishing a diagnostic and prognostic association between the outcomes reported and the used estimators. 3. The sFlt-1/PlGF ratio (cut-off point of ≤ 38) shows insufficient diagnostic accuracy to rule out PE in women with singleton pregnancies and a clinical suspicion of PE used alone. 4. In the framework of a diagnostic strategy for patients with a clinical suspicion of PE, the sFlt-1/PlGF ratio (cut-off point of ≤ 38) may help identify those women with singleton pregnancies at low risk of developing PE and other complications inherent to placental insufficiency between weeks 20 + 0 and 36 + 6 of pregnancy. Insufficient information is available regarding the cut-off points that would be applicable when stratifying the risk of developing PE in women pregnant with twin pregnancies. 5. The sFlt-1/PlGF ratio may allow the stratification of pregnant women with a clinical suspicion of PE and with a high risk of developing such disease, PE-related complications or other placental insufficiencies. 6. The sFlt-1/PlGF ratio is not useful for diagnosing (rule in) PE. 7. There is a lack of consensus regarding how to integrate determination of the sFlt-1/PlGF ratio into a diagnostic strategy, and there is a marked heterogeneity in the proposals regarding use of the test in terms of both periodicity and time interval between tests. 8. There has been identified a need to develop appropriate prognostic models that include other biochemical, clinical and ultrasound parameters to confirm that inclusion of the sFlt-1/PlGF ratio provides information that may be relevant when anticipating potential complications in the mother and/or foetus. 9. The additional use of the sFlt-1/PlGF ratio in the context of clinical evaluation of women with a clinical suspicion of PE has not been shown to have a significant influence on decision-making as hospitalisation rates remain essentially unaltered. 10. The actual role of the sFlt-1/PlGF ratio in the diagnostic strategy and its influence on clinical decisions (for example, hospitalisation) need to be determined. 11. The economic evaluations reviewed must be taken with caution given their numerous methodological limitations. Consequently, the favourable results with use of the sFlt-1/PlGF ratio to stratify risks or diagnose PE are not considered to be informative for decision-making. 12. Further economic analysis based on studies that evaluate the diagnostic accuracy of the sFlt-1/PlGF ratio incorporated into the clinical decision strategy when stratifying risks or ruling out PE should be conducted. Moreover, modelling strategies must be reproducible and appropriate to reflect the complexity of current practice when managing patients with suspected PE.

Authors' recommendations: 1. The studies identified are clinically and methodologically heterogeneous, thus limiting extrapolation of the results to our setting. Moreover, the used terminology tends to confuse the concepts of prediction, diagnosis and prognosis. 2. In general, the designs and accuracy outcomes used in these studies present serious limitations for establishing a diagnostic and prognostic association between the outcomes reported and the used estimators. 3. The sFlt-1/PlGF ratio (cut-off point of ≤ 38) shows insufficient diagnostic accuracy to rule out PE in women with singleton pregnancies and a clinical suspicion of PE used alone. 4. In the framework of a diagnostic strategy for patients with a clinical suspicion of PE, the sFlt-1/PlGF ratio (cut-off point of ≤ 38) may help identify those women with singleton pregnancies at low risk of developing PE and other complications inherent to placental insufficiency between weeks 20 + 0 and 36 + 6 of pregnancy. Insufficient information is available regarding the cut-off points that would be applicable when stratifying the risk of developing PE in women pregnant with twin pregnancies. 5. The sFlt-1/PlGF ratio may allow the stratification of pregnant women with a clinical suspicion of PE and with a high risk of developing such disease, PE-related complications or other placental insufficiencies. 6. The sFlt-1/PlGF ratio is not useful for diagnosing (rule in) PE. 7. There is a lack of consensus regarding how to integrate determination of the sFlt-1/PlGF ratio into a diagnostic strategy, and there is a marked heterogeneity in the proposals regarding use of the test in terms of both periodicity and time interval between tests. 8. There has been identified a need to develop appropriate prognostic models that include other biochemical, clinical and ultrasound parameters to confirm that inclusion of the sFlt-1/PlGF ratio provides information that may be relevant when anticipating potential complications in the mother and/or foetus. 9. The additional use of the sFlt-1/PlGF ratio in the context of clinical evaluation of women with a clinical suspicion of PE has not been shown to have a significant influence on decision-making as hospitalisation rates remain essentially unaltered. 10. The actual role of the sFlt-1/PlGF ratio in the diagnostic strategy and its influence on clinical decisions (for example, hospitalisation) need to be determined. 11. The economic evaluations reviewed must be taken with caution given their numerous methodological limitations. Consequently, the favourable results with use of the sFlt-1/PlGF ratio to stratify risks or diagnose PE are not considered to be informative for decision-making. 12. Further economic analysis based on studies that evaluate the diagnostic accuracy of the sFlt-1/PlGF ratio incorporated into the clinical decision strategy when stratifying risks or ruling out PE should be conducted. Moreover, modelling strategies must be reproducible and appropriate to reflect the complexity of current practice when managing patients with suspected PE.

Authors' methods: A literature search in Pubmed, Embase and the Cochrane Library was conducted to identify and retrieve test accuracy studies. Those that provided the best level of evidence based on their design and methodology were selected. To locate economic evaluation studies, NHS EED (CRD), Pubmed and Embase were consulted using specific filters. After removing duplicates, the remaining studies were reviewed in an initial screening based on their title and abstract. The articles selected were read in full text. For every study, the methodological quality and relevance to the aim of the health technology assessment report were evaluated.

Project Status: Completed

Year Published: 2021

URL for published report: https://www.iacs.es/wp-content/uploads/2021/10/IACS_PREECLAMPSIA-BIOMARCADORES_DEF_NIPO.pdf

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Spain

Organisation Name: Health Sciences Institute in Aragon (IACS)

Contact Address: Avda, San Juan Bosco, 13, planta 2

Contact Name: María Pilar Calvo Pérez

Contact Email: direccion.iacs@aragon.es