Original Title: Utilisation des tests incorporant le facteur de croissance placentaire (PlGF) en cas de prééclampsie soupçonnée

Authors' objectives: A request to introduce a new test to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire) was submitted to the Institut national d'excellence en santé et en services sociaux (INESSS) through the mechanism for evaluating new medical biology tests. The mandate given is to evaluate tests incorporating placental growth factor (PlGF) to help rule out or establish a diagnosis of suspected pre-eclampsia (PE) in patients between 20- and 37-weeks’ gestation. Tests incorporating PlGF include either analysis of PlGF alone, or according to the maternal serum concentration of the soluble fraction of the membrane receptor for VEGF type 1 (sFlt-1) based on an sFlt-1/PlGF ratio. The Ministère de la Santé et des Services sociaux (MSSS) therefore considers it necessary to evaluate the relevance of using tests incorporating PlGF in cases of suspected preeclampsia.

Authors' results and conclusions: RESULTS (#1 SOCIO-CULTURAL DIMENSION): The Society of Obstetricians and Gynaecologists of Canada (SOGC) and the International Society for the Study of Hypertension in Pregnancy (IHSSP) recommend the use of tests incorporating PlGF, if available, in cases of suspected preeclampsia in pregnant women. HQO also supports the reimbursement of PlGF-incorporated tests in Ontario, and NICE recommends their use in pregnant women between 20+0 and 36+6 weeks of pregnancy. Although rare, cases of maternal mortality often linked to increased pregnancy complications are on the rise in Canada. (#2 POPULATION DIMENSION): In Quebec, the incidence of preeclampsia has risen from 26.4 cases per 1,000 deliveries in 1989 to 50.6 cases in 2012. According to the SOGC, PE is gestational hypertension with new-onset proteinuria or one or more health problems - defined as maternal physiological dysfunction or evidence of uteroplacental dysfunction. PE is the cause of adverse maternal outcomes such as obvious acute kidney injury, neurological conditions, liver dysfunction, pulmonary edema, and thrombocytopenia. Preeclampsia can progress to eclampsia, characterized by maternal convulsions, or to HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) in the mother, which is one of the main causes of maternal morbidity and mortality. PE can also cause adverse fetal outcomes, including intrauterine growth retardation (IUGR), premature birth and stillbirth. (#3 CLINICAL DIMENSION): Two health technology evaluation reports and five primary studies were selected to evaluate the clinical performance of tests incorporating PlGF in predicting preeclampsia for a minimum of two weeks and a maximum of four weeks in women who were less than 35 weeks pregnant. Different thresholds were used based on the evaluation of the sFlt1/PlGF ratio or that of PlGF alone to help establish the diagnosis of PE. The sensitivity of the tests to include or predict the presence of PE was 86.44%, and positive predictive values (PPV) were generally high (PPV: 86.7% to 100%) with an sFlt-1/PlGF ratio ≥ 85. When the aim was to exclude the presence of disease for 7 to 14 days in cases of suspected PE, negative predictive values (NPV) were generally higher (PlGF: NPV = 94.8%; sFlt-1/PlGF: NPV = 99.2%) with an sFlt-1/PlGF ratio ≤ 33 or ≤ 38. In addition, tests incorporating PlGF predicted the level of PE severity with a sensitivity of 88.89%. However, a systematic review revealed that the performance of PlGF-incorporated tests may be impaired in pregnant women who have contracted COVID-19. Three studies of pregnant women with co-morbidities such as obesity, chronic hypertension, chronic kidney disease, or type 1 and 2 diabetes showed that the sensitivity of PlGF-incorporated tests decreased, both in predicting PE and its adverse maternal or fetal outcomes. (#4 ORGANIZATIONAL DIMENSION): Consultations with clinicians and nurses working with indigenous communities reveal the need to train healthcare professionals in cultural safety. In fact, it is anticipated that the benevolence of those working with indigenous patients will foster good communication between the two groups and promote the importance of obstetrical care and the use of PlGF-incorporated tests in pregnant women in these communities. No evidence was found to support the clinical utility of a systematic approach to the use of the test in the detection of gestational diabetes. According to clinicians, a post-implementation study would make it possible to measure the impact of the test in remote areas, in particular by providing information on the reduction in transportation costs, the reduction in the number of unfavorable outcomes, and the number of patients involved. (#5 ECONOMIC DIMENSION EFFICIENCY): Analysis of the economic evaluations identified in the literature suggests that tests incorporating PlGF as an adjunct to standard clinical evaluation could be efficient or costsaving compared to using standard of care alone, to rule out and rule in preeclampsia. This is more cost-effective than when they are used exclusively to rule out preeclampsia. These conclusions are limited, however, as they are highly dependent on the effect of the tests on hospitalizations and maternal and neonatal outcomes, which remain uncertain in the Quebec clinical situation. Given this uncertainty, the INESSS did not conduct de novo economic modeling. The efficiency of introducing PlGF-incorporated tests into Quebec clinical practice cannot therefore be evaluated. (#5.1 ECONOMIC DIMENSION BUDGET IMPACT ANALYSIS): According to the assumptions made, the introduction of tests incorporating PlGF into the Répertoire could entail costs of $492 K over the first three years, depending on the type of test used. It is estimated that 7,230 tests will be performed over this period. Sensitivity analyses show that the net impact of introducing PlGF tests into the Répertoire could vary from $295 K to $788 K over three years.

Authors' recommendations: In light of the above findings, the INESSS recommends that the Minister introduce tests incorporating the PlGF into the Répertoire. Details accompanying the recommendation: • The INESSS recognizes the potential of PlGF-incorporated tests in the management of suspected preeclampsia but would like to caution against the organizational challenges involved in wider implementation of these tests, particularly in remote areas that could potentially benefit more clinically. • The clinical relevance of the test may be compromised by failure to meet the required 24-hour response time. • The INESSS stresses that it would be advantageous for the MSSS to work closely with all stakeholders to optimize access to PlGF tests from an equity perspective. • The INESSS favors the creation of a multidisciplinary provincial clinical committee whose mandate would be to coordinate the collection of clinical utility data in reallife settings, and to promote the judicious use of PlGF-incorporated tests. • The designated laboratory(ies) must meet ISO 15189 requirements.

Authors' methods: The evaluation process included a review of the scientific literature, a grey literature search, and consultations with clinicians, clinical biochemists, and other stakeholders. Two technology appraisal reports by the National Institute for Health and Care Excellence (NICE) and Health Quality Ontario (HQO), published in 2022 and 2023 respectively, were identified and used as a starting point for the work. The methodology was based on six evaluation questions covering the five value dimensions: socio-cultural, population, clinical, organizational, and economic. In addition, a focus group of First Nations nurses practicing in these communities was set up to investigate issues specific to the management of preeclampsia in indigenous women, given that this is a group where the prevalence of PE can be high. A review of the economic literature was conducted, as well as an evaluation of the possibility of economic modeling to measure the efficiency of tests incorporating PlGF. A budgetary impact analysis was conducted, taking into account the costs associated with introducing PlGF-incorporated tests into the Répertoire. Costs were projected over a three-year time horizon from the perspective of the Quebec healthcare system. All scientific, contextual, and experiential data were interpreted and evaluated using a value-based approach defined according to five dimensions: sociocultural, population-based, clinical, organizational, and economic. It is also used to guide the deliberative process of the Standing Deliberative Committee (SDC) - Diagnostic Approaches and Screening, in order to develop recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/utilisation-des-tests-incorporant-le-facteur-de-croissance-placentaire-plgf-en-cas-de-preeclampsie-soupconnee.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/utilisation-des-tests-incorporant-le-facteur-de-croissance-placentaire-plgf-en-cas-de-preeclampsie-soupconnee.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)