Saliva microRNA signature to diagnose endometriosis: A cost-effectiveness evaluation of the Endotest®.

OBJECTIVE: To evaluate a saliva diagnostic test (Endotest®) for endometriosis compared with the conventional algorithm. DESIGN: A cost-effectiveness analysis with a decision-tree model based on literature data. SETTING: France. POPULATION: Women with chronic pelvic pain. METHODS: Strategy I is the French algorithm, representing the comparator. For strategy II, all patients have an Endotest®. For strategy III, patients undergo ultrasonography to detect endometrioma and patients with no endometrioma detected have an Endotest®. For strategy IV, patients with no endometrioma detected on ultrasonography undergo pelvic magnetic resonance imaging (MRI) to detect endometrioma and/or deep endometriosis. An Endotest® is then performed for patients with a negative result on MRI. MAIN OUTCOMES MEASURES: Costs and accuracy rates and incremental cost-effectiveness ratios (ICERs). Three analyses were performed with an Endotest® priced at €500, €750, and €1000. Probabilistic sensitivity analysis was conducted with Monte Carlo simulations. RESULTS: With an Endotest® priced at €750, the cost per correctly diagnosed case was €1542, €990, €919 and €1000, respectively, for strategies I, II, III and IV. Strategy I was dominated by all other strategies. Strategies IV, III and II were, respectively, preferred for a willingness-to-pay threshold below €473, between €473 and €4670, and beyond €4670 per correctly diagnosed case. At a price of €500 per Endotest®, strategy I was dominated by all other strategies. At €1000, the ICERs of strategies II and III were €724 and €387 per correctly diagnosed case, respectively, compared with strategy I. CONCLUSION: The present study demonstrates the value of the Endotest® from an economic perspective.

Cost effectiveness of the sFlt1/PlGF ratio test as an adjunct to the current practice of evaluating suspected preeclampsia in the United States.

OBJECTIVE: Preeclampsia is a major obstetric disorder that can lead to severe maternal, fetal and infant outcomes. In women with suspected preeclampsia, measurement of the soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) ratio has been shown to have a high negative predictive value (>97%). Our aim was to estimate the value to the US healthcare system of adopting this test into clinical practice. STUDY DESIGN: An economic model was developed for the evaluation of suspected preeclampsia from a US payer perspective using data from a US observational study of 459 women evaluated between 23 and 34.6 weeks. Test results were not available to clinicians. The model compares two strategies for managing suspected preeclampsia: standard care versus a biomarker-informed pathway utilizing the sFlt1/PlGF ratio. RESULTS: Utilization of the sFlt1/PlGF ratio test reduced the number of women admitted for suspected preeclampsia by 34-49%. Despite fewer admissions, a higher proportion of women admitted to hospital subsequently developed preeclampsia, and the proportion of women not admitted who would subsequently develop preeclampsia remained low (3.2%-6.7%). Cost savings arising from a reduction in admissions are estimated to be $1050 in the base case; varying the hospitalization cost ±25% would lead to savings in the range $771 to $1330 per patient at 2020 prices. CONCLUSION: Adopting the sFlt1/PlGF ratio test as an adjunct to clinical criteria improves the assessment of risk in women presenting with suspicion of preeclampsia and has the potential to safely reduce unnecessary admissions and save costs.

Placental growth factor testing for suspected pre-eclampsia: a cost-effectiveness analysis.

OBJECTIVE: To calculate the cost-effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. DESIGN: Cost-effectiveness analysis. SETTING: Eleven maternity units participating in the PARROT stepped-wedge cluster-randomised controlled trial. POPULATION: Women presenting with suspected pre-eclampsia between 20+0 and 36+6  weeks' gestation. METHODS: Monte Carlo simulation utilising resource use data and maternal adverse outcomes. MAIN OUTCOME MEASURES: Cost per maternal adverse outcome prevented. RESULTS: Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost-saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost-saving of UK£2,891,196 each year across the NHS in England. CONCLUSIONS: Clinical care with PlGF testing is associated with the potential for cost-savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre-eclampsia. TWEETABLE ABSTRACT: Placental growth factor testing for suspected pre-eclampsia is cost-saving and improves maternal outcomes.

Economic assessment of the use of the sFlt-1/PlGF ratio test to predict preeclampsia in Germany.

BACKGROUND: The 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: The 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.

Intrapartum test for detection of Group B Streptococcus colonization during labor.

PURPOSE: The purpose of this study was to evaluate the potential improvement of introducing an intrapartum test for the detection of Group B Streptococcus (GBS) during labor and to estimate its cost-effectiveness versus antepartum GBS screening culture. MATERIALS AND METHODS: Three hundred and thirteen women at beginning of labor, with unknown GBS status or with antepartum GBS screening culture were enrolled. A vaginal-rectal specimen was collected from each woman for GBS detection by real-time PCR. Results of intrapartum test and antepartum GBS screening culture were compared. RESULTS: Antepartum culture results did not always reflect the intrapartum maternal GBS colonization status since in 15.1% of the cases it was not concordant with intrapartum test. However, selecting only women, who underwent antepartum culture and intrapartum test at the same time, the percentage of concordance was 96.6%. Based on intrapartum test results, 74.9% of the total number of intrapartum antibiotic prophylaxis (IAP) was administered uselessly, while 1.9% of women did not receive IAP although they were positive to intrapartum test. Intrapartum test resulted less cost-effective than antepartum culture but it became more cost-effective at a cost threshold of about 16.00 €. CONCLUSIONS: The clinical introduction of intrapartum test could be a valuable mean for identification of GBS colonization during labor, allowing an appropriate management of mothers and neonates with consequent benefit for their health and with limited costs for Healthcare System.

Placental alpha-microglobulin-1 and combined traditional diagnostic test: a cost-benefit analysis.

OBJECTIVE: We sought to evaluate if the placental alpha-microglobulin (PAMG)-1 test vs the combined traditional diagnostic test (CTDT) of pooling, nitrazine, and ferning would be a cost-beneficial screening strategy in the setting of potential preterm premature rupture of membranes. STUDY DESIGN: A decision analysis model was used to estimate the economic impact of PAMG-1 test vs the CTDT on preterm delivery costs from a societal perspective. Our primary outcome was the annual net cost-benefit per person tested. Baseline probabilities and costs assumptions were derived from published literature. We conducted sensitivity analyses using both deterministic and probabilistic models. Cost estimates reflect 2013 US dollars. RESULTS: Annual net benefit from PAMG-1 was $20,014 per person tested, while CTDT had a net benefit of $15,757 per person tested. If the probability of rupture is <38%, PAMG-1 will be cost-beneficial with an annual net benefit of $16,000-37,000 per person tested, while CTDT will have an annual net benefit of $16,000-19,500 per person tested. If the probability of rupture is >38%, CTDT is more cost-beneficial. Monte Carlo simulations of 1 million trials selected PAMG-1 as the optimal strategy with a frequency of 89%, while CTDT was only selected as the optimal strategy with a frequency of 11%. Sensitivity analyses were robust. CONCLUSION: Our cost-benefit analysis provides the economic evidence for the adoption of PAMG-1 in diagnosing preterm premature rupture of membranes in uncertain presentations and when CTDT is equivocal at 34 to <37 weeks' gestation.

Prioritizing investments in innovations to protect women from the leading causes of maternal death.

PATH, an international nonprofit organization, assessed nearly 40 technologies for their potential to reduce maternal mortality from postpartum hemorrhage and preeclampsia and eclampsia in low-resource settings. The evaluation used a new Excel-based prioritization tool covering 22 criteria developed by PATH, the Maternal and Neonatal Directed Assessment of Technology (MANDATE) model, and consultations with experts. It identified five innovations with especially high potential: technologies to improve use of oxytocin, a uterine balloon tamponade, simplified dosing of magnesium sulfate, an improved proteinuria test, and better blood pressure measurement devices. Investments are needed to realize the potential of these technologies to reduce mortality.

Costo del proceso diagnóstico del cáncer de mama en las Unidades de Medicina Familiar del Instituto Mexicano del Seguro Social, Querétaro, México / Cost of the diagnostic process for breast cancer in the Family Medicine Units of the Mexican Social Security Institute

Objetivo: determinar el costo del proceso diagnóstico del cáncer de mama. Métodos: estudio de costos, en mujeres de 40 años y más, de enero a diciembre del 2010 de las unidades de medicina familiar del Instituto Mexicano del Seguro Social. La muestra se calculó con la fórmula de promedios para población infinita para un total de 245 mujeres. El costo se estimó mediante la técnica de tiempos y movimientos y consulta de expertos; el costo por uso de intervención se calculó con el uso promedio por intervención multiplicado por el costo unitario del mismo. El costo total del proceso diagnóstico se obtuvo de la suma de los costos de cada uno de las intervenciones. El plan de análisis incluyó promedios, porcentajes e intervalos de confianza. Resultados: el costo promedio del proceso diagnóstico fue de $852,45. Conclusión: el proceso diagnóstico de cáncer de mama incluye tamizaje y casos confirmados. El costo del proceso diagnóstico es relativamente bajo ofreciendo mejores perspectivas para el paciente y el sistema de salud.

Objective: to determine the cost of the diagnostic process for breast cancer. Methods: costs were calculated, in women 40 years and older, from January to December 2010 of the Family Medicine Units of the Mexican Social Security Institute. The sample was calculated with the formula for infinite population averages for a total of 245 women. The cost was estimated by time and motion technique and expert consultation, the intervention cost was calculated using the average usage per intervention multiplied by the unit cost thereof. The total cost of the diagnostic process was obtained from the sum of the costs of each of the interventions. The analysis plan included means, percentages and confidence interval. Results: the average cost of the diagnostic process was $852.45. Conclusions: the diagnostic process for breast cancer include screening and confirmatory cases. The cost of the diagnostic process is low, offers better prospects for the patient and the health system.

Variation in gynecological oncology follow-up practice: attributable to cancer centers or to patient characteristics? A Piedmont Regional Oncology Network Study.

AIMS AND BACKGROUND: Although guidelines recommend minimalist follow-up, there is wide variability in gynecological oncology practice. The aims of this study were to describe between-center differences in the follow-up of endometrial, ovarian, and uterine cervical cancer; to identify the determinants of test prescription; to estimate the related costs; and to assess the weight of center habits and patient characteristics as sources of unexplained variability. METHODS AND STUDY DESIGN: The medical records of patients treated between August 2004 and July 2005 for gynecological malignancies and followed up for the detection of recurrent disease were retrospectively collected from 29 centers of the Piedmont Oncology Network. Multivariate multilevel analyses were performed to study the determinants of test prescription and costs. RESULTS: Analyses were performed on 351 patients (median follow-up: 578 days). The unexplained variability in computed tomography prescriptions (26%), ultrasound prescriptions (17%), and total cost of follow-up (15%) can be attributed to center habits, independenty of the clinical characteristics of the patients. CONCLUSIONS: Much of the unexplained variability in the follow-up for gynecological malignancies is attributable to different habits of centers belonging to a cancer network. These results prompted us to design a multicenter randomized controlled trial to compare minimalist versus intensive follow-up programs in endometrial cancer.

The need for investigations to elucidate causes and effects of abnormal uterine bleeding.

This article describes a modern perspective on the basic investigations for abnormal uterine bleeding (AUB) in low-resource settings compared with a much more detailed approach for high-resource settings, bearing in mind issues of effectiveness and cost effectiveness. AUB includes any one or more of several symptoms, and it should be evaluated for the characteristics of the woman's specific bleeding pattern, her "complaint" and the presence of other symptoms (especially pain), the impact on several aspects of body functioning and lifestyle, and the underlying cause(s), especially cancer. Ideally, the evaluation is comprehensive, considering each of the potential etiological domains defined by the International Federation of Gynecology and Obstetrics PALM-COEIN system for the classification of causes. However, the detail of the questions and the extent of investigations will be significantly influenced by the technologies available and the time allotted for a consultation. In general, investigations should be performed only if they will make a material difference to the management approaches that can be offered. This should be an important consideration when a range of costly high-technology tests is accessible or when certain tests only have limited availability.

At home testing: optimizing management for the infertility physician.

OBJECTIVE: To review and describe various over-the-counter testing products available to the infertility patient, a billion-dollar a year industry that continues to grow. DESIGN: Methodology involved a detailed Medline search of literature, use of online search engines, and focused communications with various manufacturers to determine the usefulness and validity of existing products. CONCLUSION(S): Although some home tests have been subjected to scientific scrutiny, others have not. At-home testing represents an opportunity for physicians to involve patients actively in their care. When properly used, these tests also may result in cost savings. However, physicians and consumers must understand the limitations of these tests. Many of the technologies used are innovative and, with proper evaluation and implementation, could serve as valuable adjuncts to medical practice.

Pregenesys pre-eclampsia markers consensus meeting: What do we require from markers, risk assessment and model systems to tailor preventive strategies?

The Pregenesys Consensus Meeting held in Cambridge on 13 July 2009 was organized by the Pregenesys Consortium to review and critically discuss current knowledge regarding early markers of preeclampsia, to identify priorities and opportunities for future research, to consider issues that may need to be addressed in future recommendations and to highlight key issues in cost effectiveness and national policies concerning prediction and early screening for the risk of developing preeclampsia. This report summarizes the outcome of the Consensus Meeting and draws attention to issues for further investigation with specific regard to single versus multiple markers, early versus late risk identification, and the long-term effects on both maternal and perinatal health and the need to include these in any future cost-benefit assessment.

Financial impact of a novel pre-eclampsia diagnostic test versus standard practice: a decision-analytic modeling analysis from a UK healthcare payer perspective.

OBJECTIVE: Pre-eclampsia (PE), a leading cause of maternal and perinatal morbidity and mortality, is only detected after symptomatic onset. Early diagnosis may be possible with a new serum test, with resulting clinical and economic benefits versus standard practice. The authors evaluated the financial impact to the UK National Health Service (NHS). METHODS: A decision-analytic model was developed in which a cohort of 1,000 pregnant women receiving UK obstetric care was simulated. The economic impact of improved sensitivity and specificity of the novel PE test [Roche Diagnostics, Rotkreuz, Switzerland] over current diagnostic practice was modeled. While there is no specific approved diagnostic test to detect PE, physicians are using a combination of tests including blood pressure, proteinuria, Doppler, serum uric acid, etc. The novel PE test constitutes two novel biomarkers Placenta Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) which can be quantitatively analyzed using an automated system widely available in hospitals or laboratories (Elecsys/Cobas, Roche Diagnostics) and measures the levels of PlGF and sFlt-1 growth factors in pregnant women. The analysis assumed administration of the £31.13 test (the equivalent of 52 Swiss Francs [CHF]) after 20 weeks of gestation as an addition to current practice. True-positive and false-negative patients were assumed to develop mild or severe PE, eclampsia, or death. A hybrid research approach was adopted; when available, data for model inputs were obtained from published literature and public databases. Interviews with obstetricians, laboratory managers, and healthcare payers were used to validate model inputs and fill utilization-related data gaps. RESULTS: The model estimates that the costs associated with managing a typical pregnancy are £1,781 per patient when the new test is used versus £2,726 with standard practice. This represents savings of £945 per pregnant woman, if the test is used as a supplementary diagnostic tool. The savings are attributed to the new test's improved performance and its ability to better classify the pregnant patients. CONCLUSIONS: The novel test has the potential to provide substantial cost savings for NHS. Even when the novel test's cost is added to the current cost of care, the benefits exceed the additional cost, driven by the test's ability to reduce the rates of false-positive and false-negative diagnoses compared to current standard of care. Potential study limitations include the use of a pooled average of the individual sensitivities and specificities of currently used tests since no data were available on combination testing, the reliance on clinical trial data versus actual practice, and the use of clinical expert opinion when published data were unavailable.

Comparison of Papanicolaou test with visual detection tests in screening for cervical cancer and developing the optimal strategy for low resource settings.

OBJECTIVES: To compare the sensitivity, specificity, positive and negative predictive values, and accuracy of Papanicolaou test with visual inspection with acetic acid (VIA)/VIA using magnification devices (VIAM) and develop the best strategy for screening in low resource settings. MATERIALS AND METHODS: This is a prospective cross-sectional study on 408 symptomatic multiparous women in the reproductive age group, sequentially using the Papanicolaou test, the VIA, and the VIAM for screening. Women with a positive screening test underwent guided biopsy and endocervical curettage. The site of biopsy was recorded. Histopathological findings were taken as the "gold" standard in comparing the methods. RESULTS: The mean (SD) age was 32.3 (6.8) years (range, 15-49 years), whereas the mean (SD) parity was 2.9 (1.2) (range, 1-9). Abnormal cytological findings were detected in 2.9% patients, whereas the remaining smears were negative for any intraepithelial lesion or malignancy. A total of 113 cases were screened positive by one/all methods. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Papanicolaou test, the VIA, and the VIAM were 24, 98, 42, 96, and 94%; 95, 78, 19, 99, and 79%; and 95, 78, 19, 99, and 79%, respectively, for high-grade lesions. CONCLUSIONS: The Papanicolaou test had low sensitivity but high specificity, whereas visual detection methods had a high sensitivity in addition to being cheaper. Alternative methods of screening such as VIA/VIAM can be a valuable alternative to the Papanicolaou test for cervical cancer screening in low resource settings. Visual inspection using magnification devices may be of benefit over VIA in doubtful cases.

A cost-effectiveness analysis of rapid yeast detection kits.

OBJECTIVE: To determine the cost effectiveness of the utilization of over-the-counter yeast infection detection kits in the diagnosis of vaginal candidiasis. METHODS: A cost-benefit analysis based on a group of 70 adult women from a previous prospective study who presented with vaginitis symptoms. By constructing two decision trees, one in which the kits are an option to the women and one in which they are not, we predict the cost for diagnosing vaginal candidiasis in this group of women. RESULTS: For a group of 70 women presenting with vaginitis symptoms, the total cost of diagnosing their infections without the use of kits is predicted to be 7,051.10 dollars. For the same 70 women, the total of cost of diagnosing their infections with the use of kits is predicted to be 5,941.02 dollars. CONCLUSION: We conclude that the use of yeast infection detection kits could reduce the cost of diagnosis by 16%. The introduction of kits could save patients the time, money, and other resources involved in visiting a physician to confirm the diagnosis. Moreover, the sensitivity of yeast kits is superior to the traditional wet mount (77% vs. 52%), so there may be a role for the kits in the physician's office as well.

Cost effectiveness of a test to detect metastases for endometrial cancer.

OBJECTIVE: To estimate the potential cost-effectiveness of a hypothetical test to screen for lymph node metastases in women with newly diagnosed, apparent early stage endometrial cancer. METHODS: A decision model was constructed to inform a choice between the following strategies: (1) Usual care, in which the probability of undergoing full surgical staging (29%) is based on literature review; (2) Non-invasive diagnostic testing for metastasis (Testing), in which patients with abnormal test results undergo full surgical staging; (3) 100% referral, in which all patients are referred for full surgical staging. Survival was modeled using Surveillance Epidemiology and End Results (SEER) database. Base case diagnostic test characteristic estimates (sensitivity 0.90, specificity 0.90) were varied for sensitivity analysis. Cost of the diagnostic test was set at $500 and varied; costs of treatment for endometrial cancer (surgery, adjuvant therapies, diagnosis of recurrence, salvage therapies and palliative care) were incorporated. RESULTS: Usual care was the least expensive strategy, while Testing was more expensive and more effective, with an incremental cost-effectiveness ratio (ICER) of $18,785 per year of life saved (YLS) compared to Usual care. 100% referral was the most expensive and most effective strategy, with an ICER of $35,358 per YLS compared to Testing. Results are relatively sensitive to variation in test characteristics and the cost of the diagnostic test but insensitive to cost of treatment and probability of adjuvant therapies. Testing remains cost-effective compared to Usual care unless the usual rate of referral to a Gynecologic Oncologist for full staging exceeds 90%. CONCLUSIONS: Given the current low rates of full surgical staging and/or referral to a Gynecologic Oncologist, a diagnostic test to detect nodal metastasis for endometrial cancer has potential to be cost-effective when compared to usual care. Testing is also potentially cost-effective compared to 100% referral at very high test sensitivities and at the lower range of test costs.

"Shotgun" versus sequential testing. Cost-effectiveness of diagnostic strategies for vaginitis.

BACKGROUND: Although vaginitis is a common outpatient problem, only 60% of patients can be diagnosed at the initial office visit of a primary care provider using the office procedures of pH testing, whiff tests, normal saline, and potassium hydroxide preps. OBJECTIVE: To determine the most cost-effective diagnostic and treatment approach for the medical management of vaginitis. DESIGN: Decision and cost-effectiveness analyses. PARTICIPANTS: Healthy women with symptoms of vaginitis undiagnosed after an initial pelvic exam, wet mount preparations, pH, and the four criteria to diagnose bacterial vaginosis. SETTING: General office practice. METHODS: We evaluated 28 diagnostic strategies comprised of combinations of pH testing, vaginal cultures for yeast and Trichomonas vaginalis, Gram's stain for bacterial vaginosis, and DNA probes for Neisseria gonorrhoeae and Chlamydia. Data sources for the study were confined to English language literature. MEASUREMENT: The outcome measures were symptom-days and costs. RESULTS: The least expensive strategy was to perform yeast culture, gonorrhoeae and Chlamydia probes at the initial visit, and Gram's stain and Trichomonas culture only when the vaginal pH exceeded 4.9 (330 dollars, 7.30 symptom days). Other strategies cost 8 dollars to 76 dollars more and increased duration of symptoms by up to 1.3 days. In probabilistic sensitivity analysis, this strategy was always the most effective strategy and was also least expensive 58% of the time. CONCLUSIONS: For patients with vaginitis symptoms undiagnosed by pelvic examination, wet mount preparations and related office tests, a comprehensive, pH-guided testing strategy at the initial office visit is less expensive and more effective than ordering tests sequentially.