Utility of propensity score-based Bayesian borrowing of external adult data in pediatric trials: A pragmatic evaluation through a case study in acute lymphoblastic leukemia (ALL).

A fully powered randomized controlled cancer trial can be challenging to conduct in children because of difficulties in enrollment of pediatric patients due to low disease incidence. One way to improve the feasibility of trials in pediatric patients, when clinically appropriate, is through borrowing information from comparable external adult trials in the same disease. Bayesian analysis of a pediatric trial provides a way of seamlessly augmenting pediatric trial efficacy data with data from external adult trials. However, not all external adult trial subjects may be equally clinically relevant with respect to the baseline disease severity, prognostic factors, co-morbidities, and prior therapy observed in the pediatric trial of interest. The propensity score matching method provides a way of matching the external adult subjects to the pediatric trial subjects on a set of clinically determined baseline covariates, such as baseline disease severity, prognostic factors and prior therapy. The matching then allows Bayesian information borrowing from only the most clinically relevant external adult subjects. Through a case study in pediatric acute lymphoblastic leukemia (ALL), we examine the utility of propensity score matched mixture and power priors in bringing appropriate external adult efficacy information into pediatric trial efficacy assessment, and present considerations for scaling fixed borrowing from external adult data.

Predictors and adverse pregnancy outcomes associated with antepartum discharge against medical advice.

To determine predictors and pregnancy outcomes associated with antepartum discharge against medical advice (AMA D/C). Retrospective cohort study of state-level maternal and infant hospital discharge data linked to vital statistics data for antepartum admissions in California from 1995 to 2005. (N = 203,250). After adjusting for comorbid conditions, the odds of AMA D/C for Black women were twice that of white women (OR = 2.00, 95% CI 1.70-2.35). Publicly insured women had 3.5 times the odds of AMA D/C compared to privately insured women (OR = 3.54, 95% CI 3.02-4.15). AMA D/C was also higher among substance abusers and women with mental illness (OR = 1.96, 95% CI 1.43-2.67 and OR = 4.45, 95% CI 3.81-5.21 respectively). Most notably, AMA D/C tripled the odds of fetal death in patients admitted for pregnancy-induced hypertension (OR = 3.08, 95% CI 1.36-6.98) and increased the odds of neonatal morbidity (respiratory distress syndrome OR = 1.35, 95% CI 1.07-1.70 and small-for-gestational-age OR = 1.47, 95% CI 1.15-1.89) in patients admitted with preterm premature rupture of membranes. Vulnerable populations and patients with comorbid medical and mental illnesses are at increased risk for AMA D/C and its associated adverse pregnancy outcomes. Targeted interventions and resources to support at-risk populations are needed.

Factors that mediate racial/ethnic disparities in US fetal death rates.

OBJECTIVES: We sought to determine the importance of socioeconomic factors, maternal comorbid conditions, antepartum and intrapartum complications of pregnancy, and fetal factors in mediating racial disparities in fetal deaths. METHODS. We undertook a mediation analysis on a retrospective cohort study of hospital-based deliveries with a gestational age between 23 and 44 weeks in California, Missouri, and Pennsylvania from 1993 to 2005 (n = 7,104,674). RESULTS: Among non-Hispanic Black women and Hispanic women, the fetal death rate was higher than among non-Hispanic White women (5.9 and 3.6 per 1000 deliveries, respectively, vs 2.6 per 1000 deliveries; P < .01). For Black women, fetal factors mediated the largest percentage (49.6%; 95% confidence interval [CI] = 42.7, 54.7) of the disparity in fetal deaths, whereas antepartum and intrapartum factors mediated some of the difference in fetal deaths for both Black and Asian women. Among Hispanic women, socioeconomic factors mediated 35.8% of the disparity in fetal deaths (95% CI = 25.8%, 46.2%). CONCLUSIONS: The factors that mediate racial/ethnic disparities in fetal death differ depending on the racial/ethnic group. Interventions targeting mediating factors specific to racial/ethnic groups, such as improved access to care, may help reduce US fetal death disparities.

The impact of obstetric unit closures on maternal and infant pregnancy outcomes.

OBJECTIVE: To define the association between large-scale obstetric unit closures and relative changes in maternal and neonatal outcomes. DATA SOURCES/STUDY SETTING: Birth and death certificates were linked to maternal and neonatal hospital discharge records for all births between January 1, 1995 and June 30, 2005 in Philadelphia, which experienced the closure of 9 of 19 obstetric units between 1997 and 2005, and five surrounding counties and eight urban counties that did not experience a similar reduction in obstetric units. DESIGN: A before-and-after study design with an untreated control group compared changes in perinatal outcomes in Philadelphia to five surrounding control counties and eight urban control counties after controlling for case mix differences and secular trends (N = 3,140,782). RESULTS: Relative to the preclosure years, the difference in neonatal mortality (odds ratio (OR) 1.49, 95 percent CI 1.12-2.00) and all perinatal mortality (OR 1.53, 95 percent CI 1.14-2.04) increased for Philadelphia residents compared with both control groups between 1997 and 1999. After 2000, there was no statistically significant change in any outcome in Philadelphia county compared with the preclosure epoch. CONCLUSIONS: Obstetric unit closures were initially associated with adverse changes in perinatal outcomes, but these outcomes ameliorated over time.

The differential impact of delivery hospital on the outcomes of premature infants.

BACKGROUND: Because greater percentages of women deliver at hospitals without high-level NICUs, there is little information on the effect of delivery hospital on the outcomes of premature infants in the past 2 decades, or how these effects differ across states with different perinatal regionalization systems. METHODS: A retrospective population-based cohort study was constructed of all hospital-based deliveries in Pennsylvania and California between 1995 and 2005 and Missouri between 1995 and 2003 with a gestational age between 23 and 37 weeks (N = 1328132). The effect of delivery at a high-level NICU on in-hospital death and 5 complications of premature birth was calculated by using an instrumental variables approach to control for measured and unmeasured differences between hospitals. RESULTS: Infants who were delivered at a high-level NICU had significantly fewer in-hospital deaths in Pennsylvania (7.8 fewer deaths/1000 deliveries, 95% confidence interval [CI] 4.1-11.5), California (2.7 fewer deaths/1000 deliveries, 95% CI 0.9-4.5), and Missouri (12.6 fewer deaths/1000 deliveries, 95% CI 2.6-22.6). Deliveries at high-level NICUs had similar rates of most complications, with the exception of lower bronchopulmonary dysplasia rates at Missouri high-level NICUs (9.5 fewer cases/1000 deliveries, 95% CI 0.7-18.4) and higher infection rates at high-level NICUs in Pennsylvania and California. The association between delivery hospital, in-hospital mortality, and complications differed across the 3 states. CONCLUSIONS: There is benefit to neonatal outcomes when high-risk infants are delivered at high-level NICUs that is larger than previously reported, although the effects differ between states, which may be attributable to different methods of regionalization.