Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI).

BACKGROUND: The aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED). METHODS: Economic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE. RESULTS: Of the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population. CONCLUSIONS: Given the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders. CLINICALTRIALS: Trial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.

Targeted High-throughput Sequencing for Hematological Malignancies: A GBMHM Survey of Practice and Cost Evaluation in France.

The objective of this study was to assess the clinical impact and financial costs of next-generation sequencing (NGS) in 5 categories of pediatric and adult hematological cancers. NGS prescriptions were prospectively collected from 26 laboratories, with varied technical and reporting practice (all or only significant targets). Impact was defined by the identification of (1) an actionable mutation, (2) a mutation with prognostic and/or theranostic value, and/or (3) a mutation allowing nosological refinement, reported by local investigators. A microcosting study was undertaken in 4 laboratories, identifying the types and volumes of resources required for each procedural step. Individual index prescriptions for 3961 patients were available for impact analysis on the management of myeloid disorders (two thirds) and, mainly mature B, lymphoid disorders (one third). NGS results were considered to impact the management for 73.4% of prescriptions: useful for evaluation of prognostic risk in 34.9% and necessary for treatment adaptation (actionable) in 19.6%, but having no immediate individual therapeutic impact in 18.9%. The average overall cost per sample was 191 € for the restricted mature lymphoid amplicon panel. Capture panel costs varied from 369 € to 513 €. Unit costs varied from 0.5 € to 5.7 € per kb sequenced, from 3.6 € to 11.3 € per target gene/hot-spot sequenced and from 4.3 € to 73.8 € per target gene/hot-spot reported. Comparable costs for the Amplicon panels were 5-8 € per kb and 10.5-14.7 € per target gene/hot-spot sequenced and reported, demonstrating comparable costs with greater informativity/flexibility for capture strategies. Sustainable funding of precision medicine requires a transparent discussion of its impact on care pathways and its financial aspects.