Economic evaluation of the sFlt-1/PlGF ratio for the short-term prediction of preeclampsia in a Japanese cohort of the PROGNOSIS Asia study.
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SUBMITTER: Ohkuchi A
PROVIDER: S-EPMC8255211 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Two prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5-100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0-49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3-97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.
| S-EPMC8255209 | biostudies-literature
Project description:BackgroundThe PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) demonstrated that a soluble fms-like tyrosine kinase 1/placental growth factor (sFlt-1/PlGF) ratio ≤ 38 ruled out the occurrence of preeclampsia in the next week with a negative predictive value of 99.3%; a ratio > 38 indicates an increased risk of developing preeclampsia in the next 4 weeks. We performed an assessment of the economic impact of the sFlt-1/PlGF ratio test for short-term prediction of preeclampsia in Germany.MethodsWe adapted a cost-effectiveness model, which had been developed to estimate the incremental value of adding the sFlt-1/PlGF ratio test with a cut-off ratio of 38 to standard diagnostic procedures for guiding the management of women with suspected preeclampsia in the UK. We used the adapted model to estimate the incremental value of the sFlt-1/PlGF ratio test (cut-off 38) for guiding the management of women with suspected preeclampsia from a German Diagnosis-Related Group (DRG) payer perspective. The economic model estimated costs associated with diagnosis and management of preeclampsia in women managed in either a 'no-test' scenario in which clinical decisions are based on standard diagnostic procedures alone, or a 'test' scenario in which the sFlt-1/PlGF test is used in addition to standard diagnostic procedures. Test characteristics and rates of hospitalization were derived from patient-level data from PROGNOSIS. The main outcome measure from the economic model was the total cost per patient.ResultsIn the model adapted to the German DRG payer system, introduction of the sFlt-1/PlGF ratio test with a cut-off value of 38 could reduce the proportion of women hospitalized in Germany from 44.6 to 24.0%, resulting in an expected cost saving of €361 per patient.ConclusionsThe sFlt-1/PlGF ratio test is likely to reduce unnecessary hospitalization of women with a low risk of developing preeclampsia, and identify those at high risk to ensure appropriate management. Even within the restrictions of the DRG system in Germany, this results in substantial cost savings for women with suspected preeclampsia.
| S-EPMC6080558 | biostudies-literature
Project description:In Switzerland, 2.3% of pregnant women develop preeclampsia. Quantification of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio has shown a diagnostic value in the second and third trimesters of pregnancy, in particular in ruling out preeclampsia within one week. We estimated the economic impact of implementing sFlt-1/PlGF ratio evaluation, in addition to the standard of care (SOC), for women with suspected preeclampsia from a Swiss healthcare system's perspective. A decision tree model was developed to estimate direct medical costs of diagnosis and management of a simulated cohort of Swiss pregnant women with suspected preeclampsia (median week of gestation: 32) until delivery. The model compared SOC vs. SOC plus sFlt-1/PlGF ratio, using clinical inputs from a large multicenter study (PROGNOSIS). Resource use data and unit costs were obtained from hospital records and public sources. The assumed cost for sFlt-1/PlGF evaluation was €141. Input parameters were validated by clinical experts in Switzerland. The model utilized a simulated cohort of 6084 pregnant women with suspected preeclampsia (representing 7% of all births in Switzerland in 2015, n = 86,919). In a SOC scenario, 36% of women were hospitalized, of whom 27% developed preeclampsia and remained hospitalized until birth. In a sFlt-1/PlGF test scenario, 76% of women had a sFlt-1/PlGF ratio of ≤38 (2% hospitalized), 11% had a sFlt-1/PlGF ratio of >38-<85 (55% hospitalized), and 13% had a sFlt-1/PlGF ratio of ≥85 (65% hospitalized). Total average costs/pregnant woman (including birth) were €10,925 vs. €10,579 (sFlt-1/PlGF), and total costs were €66,469,362 vs. €64,363,060 (sFlt-1/PlGF). Implementation of sFlt-1/PlGF evaluation would potentially achieve annual savings of €2,105,064 (€346/patient), mainly due to reduction in unnecessary hospitalization. sFlt-1/PlGF evaluation appears economically promising in predicting short-term absence of preeclampsia in Swiss practice. Improved diagnostic accuracy and reduction in unnecessary hospitalization could lead to significant cost savings in the Swiss healthcare system.
| S-EPMC6710794 | biostudies-literature
Project description:ObjectivesTo assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia.MethodsWe used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth.ResultsIntroduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization.ConclusionsIntroducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
| S-EPMC5215695 | biostudies-literature
Project description:ObjectiveTo evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians' decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice.MethodsA multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome.ResultsIn 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001).ConclusionsThe use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.
| S-EPMC4887119 | biostudies-literature
Project description:Background The objective was to evaluate predictive performance and optimal decision threshold of the Kryptor soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio when implemented for routine management of women presenting with symptoms of preeclampsia. Methods and Results Observational retrospective study of a cohort of 501 women with suspected preeclampsia after 20 weeks of gestation. Women referred to maternity ward for observation of preeclampsia had an sFlt-1/PlGF ratio test included in routine diagnostic workup. Maternal and offspring characteristic data included maternal risk factors, outcomes, delivery mode, and indication for suspected preeclampsia. Biochemical measurements to determine sFlt-1/PlGF ratio were performed using the BRAHMS/Kryptor sFlt-1/PlGF ratio immunoassays. Results were analyzed by area under receiver-operating characteristic curve. Preeclampsia occurred in 150 of 501 (30%) of symptomatic women with an sFlt-1/PlGF ratio determined before the time of diagnosis. Area under receiver-operating characteristic curve for diagnosis of early-onset preeclampsia within 1 and 4 weeks was 0.98 (95% CI, 0.96-1.00) and 0.95 (95% CI, 0.92-0.98), respectively. For late-onset preeclampsia, predictive performance within 1 and 4 weeks was lower: 0.90 (95% CI, 0.85-0.94) and 0.85 (95% CI, 0.80-0.90), respectively. The optimal single sFlt-1/PlGF ratio threshold for all preeclampsia and late-onset preeclampsia within 1 and 4 weeks was 66. The negative and positive predictive values for ruling out and ruling in developing preeclampsia within 1 week were 96% and 70%, respectively. Conclusions The Kryptor sFlt-1/PlGF ratio is a useful clinical tool ruling out and in preeclampsia within 1 week. Prediction within 4 weeks is superior for early-onset preeclampsia. A single decision threshold of 66 is indicated for use in clinical routine.
| S-EPMC8649230 | biostudies-literature
Project description:N-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5-88.2) compared to 72.8% (95% CI 67.4-78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926-0.956) vs. 0.901 (95% CI 0.880-0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937-0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890-0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.
| S-EPMC9866466 | biostudies-literature
Project description:ObjectiveEstablish reference ranges for the Elecsys® soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies.MethodsData analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies.ResultsThe reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks' gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks' gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days' gestation.ConclusionsReference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks' gestation but appear higher in twin pregnancies thereafter.
| S-EPMC8117392 | biostudies-literature
Project description:The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n = 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to delivery. The overall prevalence of preeclampsia was 17.3%. With the use of an sFlt-1/PlGF ratio of ≤38, the negative predictive value for ruling out preeclampsia within 1 week was 97.3% [95% confidence interval (CI), 93.8-99.1], with a sensitivity of 64.3% and specificity of 85.3%. With the use of an sFlt-1/PlGF ratio of >38, the positive predictive value for ruling in preeclampsia within 4 weeks was 35.0% (95% CI, 20.6-51.7), with a sensitivity of 50.0% and specificity of 86.8%. In the analyses of the sFlt-1/PlGF ratio and fetal adverse outcomes, the area under the receiver operating characteristic curve was 92.8% (95% CI, 83.5-98.7) for ruling out fetal adverse outcomes within 1 week and 79.9% (95% CI, 68.1-90.3) for ruling in fetal adverse outcomes within 4 weeks. An sFlt-1/PlGF ratio of >38 increased the likelihood of imminent delivery 3.3-fold compared with a ratio of ≤38 [hazard ratio, 3.3 (95% CI, 2.1-5.1)]. This sub-analysis confirms the high predictive performance of the sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia in Chinese women, which may help prevent unnecessary hospitalization of women with low risk of developing preeclampsia.
| S-EPMC8419517 | biostudies-literature
Project description:Background: Aim of the study was a critical assessment of the clinical validity of the prenatal determination of sFlt-1/PlGF for preeclampsia (PE), pregnancy-induced hypertension (PIH), and proteinuria. Our analysis was based on a specificity of 95 % and a sensitivity of 82 % for the prediction of preeclampsia, as described by Elecsys (Roche). Methods: In this retrospective study the ratio of the prenatal antiangiogenic factor sFlt-1 (soluble fms-like tyrosine kinase-1) to the proangiogenic factor PIGF (placental growth factor) was analyzed using the electrochemiluminescence immunoassay of Elecsys (Roche Diagnostics, Mannheim, Germany) in 173 pregnant women. Sixty-three women with PE, 34 women with PIH and 6 women with proteinuria were compared to 72 controls. On average, the sFlt-1/PlGF ratio was determined 8 (controls), 2.4 (PE), 3.2 (PIH) and 4.1 (proteinuria) weeks before delivery. The PE and PIH cases were further subdivided into early (< 34 weeks of gestation) and late (≥ 34 weeks of gestation) onset groups. Statistical data analysis was done using the usual descriptive statistics and logistic regression analysis. ROC curves were calculated, and the sensitivity, specificity, and negative and positive predictive value (NPV, PPV) were estimated for a threshold of 85. Results: Although the specificity of the sFlt-1/PlGF ratio was high for PE, the sensitivity was low (only 59.4 %), thus giving unsatisfying results for PE. The sensitivity only increased to 62.5 % for the early-onset PE group. Intriguingly, a high ratio was detected for the combination of IUGR (intrauterine growth restriction) and PE in the early-onset PE group (8 cases). In the control group, 4 cases exceeded the cut-off value of 85 but showed no clinical signs of PE and the birth was unremarkable. In summary, we found that the sFlt-1/PIGF ratio could not be used as a predictive test for preeclampsia but rather as an indicator for the development and estimation of the severity of PE. Thus, the test is less suitable for the reliable exclusion of PE in routine clinical practice. Recommendation: The determination of the sFlT-1/PlGF ratio is only one element for PE diagnosis in addition to the measurement of blood pressure, proteinuria, ultrasound and Doppler.
| S-EPMC3864477 | biostudies-other