Cost-effectiveness of atosiban versus placebo for threatened preterm birth (APOSTEL 8 trial)

Background: To assess the cost-effectiveness of treatment with atosiban compared to placebo for threatened preterm birth from 30+0 to 33+6 weeks of gestation. Methods: We performed an economic evaluation from a societal perspective alongside the multicentre randomised controlled APOSTEL 8 trial, including 755 participants with threatened preterm birth from 30+0 to 33+6 weeks of gestation who were randomised to atosiban or placebo, of whom 752 (884 infants) were included in the intention-to-treat analysis. Costs, collected between randomisation and three months corrected child age, were measured using a combination of hospital records and the self-reported iMTA Medical and Productivity Cost Questionnaires and estimated at infant level. The main outcome measure was cost-effectiveness expressed in terms of incremental cost per severe adverse neonatal outcome prevented. Multiple imputation by chained equations was used to handle missing data. Non-parametric bootstrapping was used to estimate statistical uncertainty surrounding incremental cost-effectiveness outcomes. Findings: The difference in mean costs between the atosiban group (€40,743.1) and the placebo group (€40,793.6) was not statistically significant (mean difference: -€50.5; 95% confidence interval (CI) −4037.6 to 3936.7). The incremental cost per severe adverse neonatal outcome prevented was dominant (-€5286.6), falling in the south-east quadrant of the cost-effectiveness plane, indicating cost-savings and reduced severe adverse neonatal outcomes by atosiban. However, the bootstrapped cost-effect pairs were distributed across all four quadrants of the cost-effectiveness plane, indicating high uncertainty surrounding cost-effectiveness estimates. The probability of cost-effectiveness of atosiban reached 50% at a willingness to pay threshold of €33,023.3 per severe adverse neonatal outcome prevented. Interpretation: This economic evaluation did not demonstrate that atosiban is a cost-effective treatment for threatened PTB from 30+0 to 33+6 weeks gestation. In addition to the absence of clinical benefit, our findings show no economic advantage, further discouraging its routine use at this gestational age. These results contribute to optimizing evidence-based management of threatened preterm birth.