Discovery of disease-causing structural variants (dcSV) from whole genome sequencing data is difficult due to high number of false positives and a lack of efficient way to estimate allele frequency. Here we introduce SVRare, an application that aggregates structural variants (SV) called by other tools, and efficiently annotates rare SVs to aid dcSVs discovery. Applied in the Genomics England (GEL) research environment to data from the 100K Genomes Project, SVRare aggregated 554,060,126 SVs called by Manta and Canvas in all the 71,408 participants in the rare-disease arm. From a pilot study of 4313 families, SVRare identified 36 novel protein-coding disrupting SVs on diagnostic grade genes that may explain proband's phenotype. It is estimated that SVRare can increase SV-based diagnosis yield by at least 4-fold. We also performed a genome-wide association study, and uncovered clusters of dcSVs in genes with known pathogenicity, such as PKD1/2 - cystic kidney diseases and LDLR - familial hypercholesterolaemia.
Anti-vascular endothelial growth factor (anti-VEGF) injections have revolutionised vision for patients with macular degeneration or diabetic macular oedema. However, the choice of anti-VEGF is controversial. Two drugs licensed for macular oedema are ranibizumab (Lucentis) and aflibercept (Eylea). A third drug, bevacizumab (Avastin), is only licensed for colorectal cancer, and therefore, use in the eye is 'off label'. 1 Yet, all three are effective. Independently supported randomised controlled trials, 2,3 and systematic reviews were unable to find a significant difference in safety or efficacy. 4,5 The cost difference is significant however. Prices, according to the British National Formulary (BNF), are: ranibizumab; £742 per single injection vial, aflibercept; £816 per single injection vial; bevacizumab £242.66 per vial, but in practice each bevacizumab vial is divided into 20 injections, giving a price of £12.13 per injection. 6 In each case, these costs are multiplied many times over, because patients require repeated injections. Given the current government's cost-cutting ambitions, 7 we hypothesised the majority of injections would use the less expensive drug, bevacizumab. We therefore performed a freedom of information (FOI) request to all UK NHS ophthalmological units for the number of ranibizumab, aflibercept, and bevacizumab injections prescribed during January 2015 (Table 1 and Figure 1). These results indicate the anti-VEGF injection cost to the NHS. Contrary to the hypothesis, the vast majority (97%) were with the more expensive drugs ranibizumab and aflibercept. If all injections used divided bevacizumab, the estimated cost would be £607 749 (£729 500 incl. VAT) saving the NHS £449 196 354 (£539 035 492 incl. VAT) per year. With 5% unaccounted for, savings may be greater.
PurposeThe difference in cost of Anti‐vascular endothelial growth factor (anti‐VEGF) injections is significant. Prices, according to the British National Formulary (BNF), are: ranibizumab; £742 per single injection vial, aflibercept; £816 per single injection vial, and bevacizumab £242.66, but in standard practice each vial is divided into 20 injections, giving a price of £12.13 per injection. Because patients require repeated injections these costs are multiplied many times over.We hypothesised the majority of injections would be with the less expensive drug, bevacizumab. We therefore performed a survey of all United Kingdom (UK) NHS ophthalmological units.MethodsA freedom of information (FOI) request was submitted to all UK NHS Trusts and Health Boards requesting the number and cost of intravitreal injections of ranibizumab, aflibercept, and bevacizumab prescribed during the month of January 2015. Non‐NHS units were excluded.Costs per month were determined by multiplying injection numbers with BNF (British National Formulary) prices and then by 12 for yearly costs.ResultsA total of 189 FOI requests were sent. The overall response rate was 95.8%.Ranibizumab was used 30,634 times (61%), Aflibercept 18,095 (36%) and Avastin was only 1410 (3%).Costs per month were: £27,276,514 for Ranibizumab, £17,683,373 for Aflibercept, £20,530 for Bevacizumab.Total monthly costs were: £44,980,416.00. Estimated annual costs were: £539,764,992.00.ConclusionsThese results show the anti‐VEGF injection cost to the NHS. Contrary to hypothesis the vast majority (97%) were still with the more expensive drugs ranibizumab and aflibercept. If all injections used divided bevacizumab, the estimated drug cost would be £607,749 (£729,500 incl. VAT) saving the NHS £449,196,354 (£539,035,492 incl. VAT) per year. With 5% remaining unaccounted for the savings may be greater.
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