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Background Partners from an NGO, academia, industry and government applied a tool originating in the private sector - Quantitative Decision Making (QDM) - to rigorously assess whether to invest in testing a global health intervention. The proposed NEWBORN study was designed to assess whether topical emollient therapy with sunflower seed oil in infants with very low birthweight <1500 g in Kenya would result in a significant reduction in neonatal mortality compared to standard of care. Methods The QDM process consisted of prior elicitation, modelling of prior distributions, and simulations to assess Probability of Success (PoS) via assurance calculations. Expert opinion was elicited on the probability that emollient therapy with sunflower seed oil will have any measurable benefit on neonatal mortality based on available evidence. The distribution of effect sizes was modelled and trial data simulated using Statistical Analysis System to obtain the overall assurance which represents the PoS for the planned study. A decision-making framework was then applied to characterise the ability of the study to meet pre-selected decision-making endpoints. Results There was a 47% chance of a positive outcome (defined as a significant relative reduction in mortality of ≥15%), a 45% chance of a negative outcome (defined as a significant relative reduction in mortality <10%), and an 8% chance of ending in the consider zone (ie, a mortality reduction of 10 to <15%) for infants <1500 g. Conclusions QDM is a novel tool from industry which has utility for prioritisation of investments in global health, complementing existing tools (eg, Child Health and Nutrition Research Initiative). Results from application of QDM to the NEWBORN study suggests that it has a high probability of producing clear results. Findings encourage future formation of public-private partnerships for health. [ABSTRACT FROM AUTHOR]

Objective: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. Method: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life‐threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. Results: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. Conclusions: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety. Key points: What's already known about this topic? Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive AE framework in pregnancy trials severely limits understanding risks in pregnant women What does this study add? Through international consensus we systematically developed definitions and severity grading for maternal and foetal AEs: Maternal and Fetal AE Terminology Version 1.0. New fetal AE definitions were adopted by the Medical Dictionary for Regulatory Activities. This terminology should be used to monitor safety in pregnancy trials [ABSTRACT FROM AUTHOR]

Aim: Recent evidence is emerging indicating long-term effects in infants born after an episode of preterm labour (PTL), even if birth is at term. This population-based study compared long-term rates of outcomes and health-care utilisation (HCU) in children born following spontaneous preterm labour, irrespective of gestational age at delivery or of an uncomplicated pregnancy (SPTLu), with children born following full-term labour (FTL), overall stratified by comorbidity status and assessed using a composite morbidity measure (CM).Methods: Retrospective data on mother-neonate pairs were collected from a patient-linked dataset from the Netherlands Perinatal Registry and the PHARMO Database Network. Children born between 2000 and 2010 were followed until 2012.Results: Of pregnancies in 134 006 mother-neonate pairs, 122 894 (92%) pregnancies resulted in FTL, and 11 112 (8%) resulted in PTL. Of the PTL pregnancies, 6599 (59%) were SPTLu. Mean follow-up after birth was 6.6-6.7 years. Children from SPTLu pregnancies were at increased risk of neurodevelopmental and respiratory conditions compared with those from FTL pregnancies. In children from SPTLu pregnancies, the presence of the CM was associated with an increased risk of respiratory conditions and failure to thrive. Post-natal hospitalisations (incidence rate (IR) per 100 patient-years: 18.1 vs. 11.7) and specialist referrals (IR per 1000 patient-years: 290.6 vs. 184.5) occurred significantly more frequently in children from SPTLu versus FTL pregnancies.Conclusion: The increased risk of morbidities and HCU in children born following SPTLu pregnancy in this population-based setting reinforces the need for safe interventions that can effectively halt labour and lead to an improvement in childhood outcomes. [ABSTRACT FROM AUTHOR]

Aim The aim was to investigate the efficacy and safety of intravenous retosiban in women with spontaneous preterm labour. Methods This was a randomized, double-blind, placebo-controlled, phase 2 trial. Retosiban was administered intravenously for 48 h to women in spontaneous preterm labour between 300/7 and 356/7 weeks' gestation with an uncomplicated singleton pregnancy in an in-patient obstetric unit. Outcome measures were uterine quiescence (primary endpoint), days to delivery, preterm delivery and safety. Results Uterine quiescence was achieved in 62% of women who received retosiban ( n = 30) compared with 41% who received placebo ( n = 34). The relative risk (RR) was 1.53 (95% credible interval [CrI] 0.98, 2.48; NS). Retosiban resulted in a significant increase in time to delivery compared with placebo (mean difference 8.2 days, 95% CrI 2.7, 13.74). This difference was consistent across all gestational ages. The proportion of preterm births in the retosiban and placebo groups was 18.7% (95% CrI 7.4%, 33.7%) and 47.2% (95% CrI 31.4%, 63.4%), respectively. The RR of preterm birth in women treated with retosiban was 0.38 (95% CrI 0.15, 0.81). There were no deliveries within 7 days in the retosiban group, but there were six (17.6%) births in the placebo group. The maternal, fetal and neonatal adverse events were comparable in the retosiban and placebo groups. Conclusions Intravenous administration of retosiban in women with spontaneous preterm labour was associated with a greater than 1 week increase in time to delivery compared with placebo, a significant reduction in preterm deliveries, a non-significant increase in uterine quiescence and a favourable safety profile. [ABSTRACT FROM AUTHOR]