Market access to new anticancer medicines for children and adolescents with cancer in Europe

Background and aims: There is an alarming delay in Europe for anticancer medicines becoming accessible for children. Following a paediatric European Union marketing authorisation, national Health Technology Assessment (HTA) agencies evaluate effectiveness, and safety of medicines to support decision on their cost and reimbursement. This study (a SIOPE Access to Medicines project) aimed to evaluate how these HTA evaluations take place for anticancer medicines indicated for paediatric use in Europe and to explore where the delays for market access originate. Methods: We obtained HTA reports from the public domain for nine European countries for blinatumomab, dinutuximab beta and tisagenlecleucel. We evaluated the time elapsed between marketing authorisation for a paediatric indication and a national HTA decision and the nature of the decision. Results: Out of 23 HTA decisions (four countries without blinatumomab report), 18 were positive, two with restrictions, three negative. For blinatumomab, tisagenlecleucel and dinutuximab beta, the median time to an HTA decision after regulatory approval for paediatric use was 353 days (range 193–751), 141 days (range 77–517) and 515 days (range 0–780), respectively, with variability between countries. Dinutuximab beta and tisagenlecleucel were first introduced in children, but did not result in shorter time to HTA decision. For blinatumomab, marketing authorisation followed 1008 days after the indication in adults, with HTA applications submitted a median of 167 days later, and a recommendation after 145 days. Conclusions: This study reveals ample variability in HTA decision making in nine European Union countries. Collaboration and alignment of required evidence is needed to facilitate robust scientific HTA assessments, also considering methodological challenges in paediatric oncology

Cost-effectiveness of whole-exome sequencing in progressive neurological disorders of children

ObjectivesTo clarify the diagnostic utility and the cost-effectiveness of whole-exome sequencing (WES) as a routine early-diagnostic tool in children with progressive neurological disorders.MethodsPatients with infantile-onset severe neurological diseases or childhood-onset progressive neurological disorders were prospectively recruited to this WES study, in the pediatric neurology clinic at Helsinki University Hospital during 2016–2018. A total of 48 patients underwent a singleton WES. A control group of 49 children underwent traditional diagnostic examinations and were retrospectively collected from the hospital records. Their use of health care services, related to the diagnostic process, was gathered. Incremental cost-effectiveness ratio (ICER) per additional diagnosis was calculated from the health care provider perspective. Bootstrapping methods were used to estimate the uncertainty of cost-effectiveness outcomes.ResultsWES provided a better diagnostic yield (38%) than diagnostic pathway that did not prioritize WES in early diagnosis (25%). WES outperformed other diagnostic paths especially when made early, within one year of first admission (44%). Cost-effectiveness in our results are conservative, affected by WES costs during 2016–18.ConclusionsWES is an efficient and cost-effective diagnostic tool that should be prioritized in early diagnostic path of children with progressive neurological disorders. The progressively decreasing price of the test improves cost-effectiveness further.</div

Market access to new anticancer medicines for children and adolescents with cancer in Europe

Background and aims: There is an alarming delay in Europe for anticancer medicines becoming accessible for children. Following a paediatric European Union marketing authorisation, national Health Technology Assessment (HTA) agencies evaluate effectiveness, and safety of medicines to support decision on their cost and reimbursement. This study (a SIOPE Access to Medicines project) aimed to evaluate how these HTA evaluations take place for anticancer medicines indicated for paediatric use in Europe and to explore where the delays for market access originate. Methods: We obtained HTA reports from the public domain for nine European countries for blinatumomab, dinutuximab beta and tisagenlecleucel. We evaluated the time elapsed between marketing authorisation for a paediatric indication and a national HTA decision and the nature of the decision. Results: Out of 23 HTA decisions (four countries without blinatumomab report), 18 were positive, two with restrictions, three negative. For blinatumomab, tisagenlecleucel and dinutuximab beta, the median time to an HTA decision after regulatory approval for paediatric use was 353 days (range 193–751), 141 days (range 77–517) and 515 days (range 0–780), respectively, with variability between countries. Dinutuximab beta and tisagenlecleucel were first introduced in children, but did not result in shorter time to HTA decision. For blinatumomab, marketing authorisation followed 1008 days after the indication in adults, with HTA applications submitted a median of 167 days later, and a recommendation after 145 days. Conclusions: This study reveals ample variability in HTA decision making in nine European Union countries. Collaboration and alignment of required evidence is needed to facilitate robust scientific HTA assessments, also considering methodological challenges in paediatric oncology

Medical costs of children admitted to the neonatal intensive care unit: The role and possible economic impact of WES in early diagnosis

It has been estimated that at least 6.0% of neonates admitted to the Neonatal Intensive Care Unit remains genetically undiagnosed because genetic testing is not routinely performed. The objective of this study is to provide an overview of average healthcare costs for patients admitted to the Neonatal Intensive Care Unit and to assess possible impact of implementing Whole Exome Sequencing (WES) on these total healthcare costs. Hereto, we retrospectively collected postnatal healthcare data of all patients admitted to the level IV Neonatal Intensive Care Unit at the Radboudumc (October 2013–October 2015) and linked unit costs to these healthcare consumptions. Average healthcare costs were calculated and a distinction between patients was made based on performance of genetic tests and the presence of congenital anomalies. Overall, on average €26,627 was spent per patient. Genetic costs accounted for 2.3% of all costs. Healthcare costs were higher for patients with congenital anomalies compared to patients without congenital anomalies. Patients with genetic diagnostics were also more expensive than patients without genetic diagnostics. We next modelled four scenarios based on clinical preselection. First, when performing trio-WES for all patients instead of current diagnostics, overall healthcare costs will increase with 22.2%. Second, performing trio-WES only for patients with multiple congenital anomalies will not result in any cost changes, but this would leave patients with an isolated congenital anomalies untested. We therefore next modelled a scenario performing trio-WES for all patients with congenital anomalies, increasing the average per patient healthcare costs by 5.3%. This will rise to a maximum of 5.5% when also modelling for an extra genetic test for clinically selected patients to establish genetic diagnoses that are undetectable by WES. In conclusion, genetic diagnostic testing accounted for a small fraction of total costs. Implementation of trio-WES as first-tier test for all patients with congenital anomalies will lead to a limited increase in overall healthcare budget, but will facilitate personalized treatments options guided by the diagnoses made