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

Objectives: To 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. Methods: Patients 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. Results: WES 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. Conclusions: WES 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. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.Peer reviewe

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

Whole-exome sequencing in intellectual disability; cost before and after a diagnosis

Clinical application of whole-exome and whole-genome sequencing (WES and WGS) has led to an increasing interest in how it could drive healthcare decisions. As with any healthcare innovation, implementation of next-generation sequencing in the clinic raises questions on affordability and costing impact for society as a whole. We retrospectively analyzed medical records of 370 patients with ID who had undergone WES at various stages of their diagnostic trajectory. We collected all medical interventions performed on these patients at the University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. We categorized the patients according to their WES-based preliminary diagnosis ("yes", "no", and "uncertain"), and assessed the per-patient healthcare activities and corresponding costs before (pre) and after (post) genetic diagnosis. The WES-specific diagnostic yield among the 370 patients was 35% (128 patients). Pre-WES costs were €7.225 on average. Highest average costs were observed for laboratory-based tests, including genetics, followed by consults. Compared to pre-WES costs, the post-WES costs were on average 80% lower per patient, irrespective of the WES-based diagnostic outcome. Application of WES results in a considerable reduction of healthcare costs, not just in current settings, but even more so when applied earlier in the diagnostic trajectory (genetics-first). In such context, WES may replace less cost-effective traditional technologies without compromising the diagnostic yield. Moreover, WES appears to harbor an intrinsic "end-of-trajectory" effect; regardless of the diagnosis, downstream medical interventions decrease substantially in both number and costs

Whole-exome sequencing in intellectual disability; cost before and after a diagnosis

Clinical application of whole-exome and whole-genome sequencing (WES and WGS) has led to an increasing interest in how it could drive healthcare decisions. As with any healthcare innovation, implementation of next-generation sequencing in the clinic raises questions on affordability and costing impact for society as a whole. We retrospectively analyzed medical records of 370 patients with ID who had undergone WES at various stages of their diagnostic trajectory. We collected all medical interventions performed on these patients at the University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. We categorized the patients according to their WES-based preliminary diagnosis ("yes", "no", and "uncertain"), and assessed the per-patient healthcare activities and corresponding costs before (pre) and after (post) genetic diagnosis. The WES-specific diagnostic yield among the 370 patients was 35% (128 patients). Pre-WES costs were €7.225 on average. Highest average costs were observed for laboratory-based tests, including genetics, followed by consults. Compared to pre-WES costs, the post-WES costs were on average 80% lower per patient, irrespective of the WES-based diagnostic outcome. Application of WES results in a considerable reduction of healthcare costs, not just in current settings, but even more so when applied earlier in the diagnostic trajectory (genetics-first). In such context, WES may replace less cost-effective traditional technologies without compromising the diagnostic yield. Moreover, WES appears to harbor an intrinsic "end-of-trajectory" effect; regardless of the diagnosis, downstream medical interventions decrease substantially in both number and costs

Whole-exome sequencing in intellectual disability; cost before and after a diagnosis

Clinical application of whole-exome and whole-genome sequencing (WES and WGS) has led to an increasing interest in how it could drive healthcare decisions. As with any healthcare innovation, implementation of next-generation sequencing in the clinic raises questions on affordability and costing impact for society as a whole. We retrospectively analyzed medical records of 370 patients with ID who had undergone WES at various stages of their diagnostic trajectory. We collected all medical interventions performed on these patients at the University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. We categorized the patients according to their WES-based preliminary diagnosis ("yes", "no", and "uncertain"), and assessed the per-patient healthcare activities and corresponding costs before (pre) and after (post) genetic diagnosis. The WES-specific diagnostic yield among the 370 patients was 35% (128 patients). Pre-WES costs were €7.225 on average. Highest average costs were observed for laboratory-based tests, including genetics, followed by consults. Compared to pre-WES costs, the post-WES costs were on average 80% lower per patient, irrespective of the WES-based diagnostic outcome. Application of WES results in a considerable reduction of healthcare costs, not just in current settings, but even more so when applied earlier in the diagnostic trajectory (genetics-first). In such context, WES may replace less cost-effective traditional technologies without compromising the diagnostic yield. Moreover, WES appears to harbor an intrinsic "end-of-trajectory" effect; regardless of the diagnosis, downstream medical interventions decrease substantially in both number and costs

Whole-exome sequencing in intellectual disability; cost before and after a diagnosis

Clinical application of whole-exome and whole-genome sequencing (WES and WGS) has led to an increasing interest in how it could drive healthcare decisions. As with any healthcare innovation, implementation of next-generation sequencing in the clinic raises questions on affordability and costing impact for society as a whole. We retrospectively analyzed medical records of 370 patients with ID who had undergone WES at various stages of their diagnostic trajectory. We collected all medical interventions performed on these patients at the University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. We categorized the patients according to their WES-based preliminary diagnosis ("yes", "no", and "uncertain"), and assessed the per-patient healthcare activities and corresponding costs before (pre) and after (post) genetic diagnosis. The WES-specific diagnostic yield among the 370 patients was 35% (128 patients). Pre-WES costs were €7.225 on average. Highest average costs were observed for laboratory-based tests, including genetics, followed by consults. Compared to pre-WES costs, the post-WES costs were on average 80% lower per patient, irrespective of the WES-based diagnostic outcome. Application of WES results in a considerable reduction of healthcare costs, not just in current settings, but even more so when applied earlier in the diagnostic trajectory (genetics-first). In such context, WES may replace less cost-effective traditional technologies without compromising the diagnostic yield. Moreover, WES appears to harbor an intrinsic "end-of-trajectory" effect; regardless of the diagnosis, downstream medical interventions decrease substantially in both number and costs

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

PURPOSE: This study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients' diagnostic trajectory in order to evaluate early WES implementation. METHODS: We compared 17 patients' trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool. RESULTS: WES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the$3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and$1,727 for genetic investigations in undiagnosed patients. CONCLUSION: The increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and cost-efficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value-based research into diagnostics