Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort.

OBJECTIVES: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. METHODS: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p < .05). RESULTS: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs' point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. CONCLUSIONS: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.

Preterm birth, defined as delivery before 37 weeks' gestation, is the leading cause of illness and death in newborns. In the United States, more than 10% of infants are born prematurely, and this rate is substantially higher in lower-income, inner-city and Black populations. Prematurity associates with greatly increased risk of short- and long-term medical complications and can generate significant costs throughout the lives of affected children. Annual U.S. health care costs to manage short- and long-term prematurity complications are estimated to exceed $25 billion.Clinical interventions, including case management (increased patient outreach, education and specialist care), pharmacological treatment and their combination can provide benefit to pregnancies at higher risk for preterm birth. Early and sensitive risk detection, however, remains a challenge.We have developed and validated a proteomic biomarker risk predictor for early identification of pregnancies at increased risk of preterm birth. The ACCORDANT study modeled treatments with real-world patient data from a racially and ethnically diverse U.S. population to compare the benefits of risk predictor testing plus clinical intervention for higher-risk pregnancies versus no testing and standard care. Measured outcomes included neonatal and maternal length of hospital stay, associated costs and neonatal morbidity and mortality. The model projected improved outcomes and reduced costs across all subjects, including ethnic and racial minority populations, when predicted higher-risk pregnancies were treated using case management with or without pharmacological treatment. The biomarker risk predictor shows high potential to be a clinically important component of risk stratification for pregnant women, leading to tangible gains in reducing the impact of preterm birth.

South Carolina Partners for Preterm Birth Prevention: a regional perinatal initiative for the reduction of premature birth in a Medicaid population.

OBJECTIVE: The objective of the study was to improve the distribution of preterm deliveries in a Medicaid population through a regional perinatal risk assessment and case management initiative. STUDY DESIGN: An innovative public/private partnership was initiated in the 8 county Lowcountry (LC) perinatal region to reduce preterm birth (PTB) among Medicaid recipient women. Eligible women were identified and underwent telephonic risk assessment, education, and access to a 24 hours, 7 days per week perinatal hotline. Women with predetermined risk factors for PTB were offered patient-centered case management. Medicaid claims and birth certificate data were used to compare obstetric outcomes for 2006 (intervention) and 2004 (control) in both the Lowcountry (LC; program) and Midlands (ML; nonprogram) perinatal regions. RESULTS: There were 6356 Medicaid deliveries in the LC in 2006. Of these, 2111 were referred for telephonic risk assessment; 317 had identifiable PTB risk factors and consented to case management. Compared with 2004, there was a significant improvement in the distribution of preterm birth (P = .05) in the LC region, primarily confined to deliveries less than 28 weeks (1.6% vs 1.1%; P = .029, relative risk [RR] 0.75, 95% confidence interval [CI], 0.51-0.96). There were also reductions in the frequency (6.7% vs 5.8%; RR 0.86, 95% CI, 0.75-0.98; P = .04) and mean duration (25.0 vs 20.6 days; 95% CI, 1.03-7.77; P = .01) of neonatal intensive care unit (NICU) admissions. No changes were identified in the ML region. CONCLUSION: A regional initiative of telephonic risk assessment and case management of Medicaid recipient women significantly reduced deliveries less than 28 weeks and NICU care.