Background The approval of oncology therapies has increasingly incorporated biomarker-driven precision medicine. However, the influence of mandatory biomarker selection on regulatory pathways remains poorly understood. We compared the regulatory characteristics of targeted and non-targeted oncology therapies first authorised in the European Union between 2015 and 2025. Methods We conducted a retrospective analysis of drug–indication pairs for malignant solid tumours first authorised following EMA assessment and European Commission marketing authorisation between January 2015 and December 2025. Therapies were classified as targeted when mandatory biomarker testing was required for patient selection in the approved indication. Regulatory characteristics and timelines were obtained from publicly available EMA information. The primary regulatory outcome was Conditional Marketing Authorisation (CMA). Results Eighty drug–indication pairs were included: 45 targeted (56.3%) and 35 non-targeted (43.8%). No significant linear temporal trend in the proportion of targeted therapies was detected (OR per year 1.15; 95% CI 1.00–1.33; p = 0.051). CMA was granted to 42.2% of targeted versus 5.7% of non-targeted therapies (OR 12.06; 95% CI 2.57–56.53; p < 0.001). The association remained directionally consistent across sensitivity analyses accounting for calendar year, pharmacological class, tumour type, and multiple indications within the same application. No significant difference in total elapsed time to marketing authorisation was detected (median 419 vs 427 days; median difference − 8days; 95% bootstrap CI −52–21). Conclusions Targeted oncology therapies requiring mandatory biomarker selection were substantially more likely than non-targeted therapies to receive CMA, although the magnitude of the association was imprecisely estimated. Policy summary Greater use of CMA among targeted therapies means that more indications enter the post-authorisation period with confirmatory evidence obligations outstanding. This may be relevant to HTA and reimbursement decisions and warrants longitudinal research on how these obligations and the evidence base evolve after authorisation.
Introduction Weekend admissions have been associated with worse health outcomes compared with weekday admissions. Our study assessed the association between weekend admission and early in-hospital mortality among patients with hematologic malignancies and febrile neutropenia. We further evaluated whether septic shock mediates this relationship, regardless of length of in-hospital stay. Methods We conducted a retrospective analysis of the 2016–2020 NIS database identifying patients with febrile neutropenia and hematologic malignancies using ICD-10 codes. Weekend admission was the primary exposure, while 3- and 7-day in-hospital mortality were the study outcomes. Generalized linear models estimated the association between weekend admission and each outcome, adjusting for sociodemographic characteristics, comorbidities, cancer type, elective admission status and length of stay. Results Among 45,540 patients in this study, 57% were male, 65% were white and the mean age was 51 years. Weekend admission was significantly associated with a higher risk of 3-day (RR=1.48; 95%CI: [1.21–1.83]) and 7-day mortality (RR=1.32; 95%CI: [1.12–1.56]). Mediation analysis demonstrated that septic shock significantly mediated the association between weekend admission and overall in-hospital mortality – indirect effect (RR=1.03; 95% CI [1.01–1.04]), whereas the direct effect and overall effect of weekend admission on mortality were not statistically significant. Conclusion Weekend admission was associated with a higher risk of early in-hospital mortality. Septic shock partially mediated this relationship when assessed across the entire in-hospital stay. The absence of a direct weekend effect suggests that health system-level factors contributing to septic shock may represent key intervention targets to improve mortality outcomes in this high-risk population.
Background The US Food and Drug Administration (FDA) can grant earlier access to promising therapies through its accelerated approval pathway, conditional on post-authorisation trials confirming clinical benefit. Between 1 January 2010 and 31 December 2024, the FDA granted accelerated approval to 59 haematological malignancy drug indications, 13 of which were subsequently withdrawn because of unconfirmed clinical benefit or safety concerns. Methods We assessed the regulatory status and reimbursement recommendations for these 13 FDA-withdrawn drug indications in Australia, Canada, and England using publicly available regulatory and health technology assessment (HTA) data. Results Eight of the 13 FDA-withdrawn drug indications were approved in at least one comparison jurisdiction, resulting in 14 marketing authorisations overall. Three of 14 were subsequently withdrawn. As of June 2025, 11 authorisations remained active, of which only five had received positive reimbursement recommendations. Conclusion Many haematological malignancy drug indications withdrawn from FDA accelerated approval remain authorised in other jurisdictions, with a minority continuing to receive positive reimbursement recommendations. Differences in regulatory and reimbursement decisions across jurisdictions may reflect variation in pathway use, post-authorisation evidence requirements, authorised indications, and interpretation of evidence. Policy Summary The continued authorisation of haematological malignancy drug indications in Australia, Canada, and England following FDA withdrawal of comparable indications has important implications for patients and health systems. Continued approval for the indication may facilitate use of the drug in patients with refractory disease and few alternatives, but may also expose patients to treatments with no clear evidence of clinical benefit or for which safety concerns altered the benefit-risk assessment. Continued public reimbursement under such conditions could also lead to unnecessary spending for health systems. Major new evidence or regulatory action in a comparable jurisdiction should prompt proportionate reassessment of local authorisation and reimbursement decisions, with consideration of differences in the authorised indication and applicable evidence.
