Identifying the ancestral components of genomes of admixed individuals helps uncovering the genetic basis of diseases and understanding the demographic history of populations. We estimate local ancestry on 313 Chileans and assess the contribution from three continental populations. The distribution of ancestry block-length suggests an average admixing time around 10 generations ago. Sex-chromosome analyses confirm imbalanced contribution of European men and Native-American women. Previously known genes under selection contain SNPs showing large difference in allele frequencies. Furthermore, we show that assessing ancestry is harder at SNPs with higher recombination rates and easier at SNPs with large difference in allele frequencies at the ancestral populations. Two observations, that African ancestry proportions systematically decrease from North to South, and that European ancestry proportions are highest in central regions, show that the genetic structure of Chileans is under the influence of a diffusion process leading to an ancestry gradient related to geography.

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Background The introduction of human epidermal growth factor receptor 2 (HER2)-targeted treatment options, including dual HER2 blockade, has improved the prognosis for patients with HER2-positive breast cancer (BC) substantially. However, most of these treatments are administered via the intravenous (IV) route, which can present many challenges, such as long infusion and observation times, issues associated with repeated IV access, and increased strain on time and resources of medical centers and healthcare professionals. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous (SC) injection (pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO ® , F. Hoffmann-La Roche Ltd, Basel, Switzerland; PH FDC SC)) has been approved for use alongside chemotherapy for early-stage and metastatic HER2-positive BC. Objectives This systematic literature review was performed to identify evidence relating to time/resource use and resulting cost differences between SC and IV administration of oncology biologics in a hospital setting, and, ultimately, to inform economic modeling and associated health technology assessment of PH FDC SC. Methods Electronic databases (Embase, MEDLINE, and EconLit) were searched on 9 April 2020. Additional hand searches were performed to identify publications not captured in the electronic database search. Publication screening and data extraction (study characteristics, participants, interventions, costs, and time/resource use) were carried out per the standard Cochrane review methodology. The quality of economic evidence of cost analyses was assessed using the 36-item checklist of the National Institute for Health and Care Excellence Single Technology Appraisal Specification for submission of evidence (January 2015). Results The database search identified 2,740 records, of which 237 underwent full text screening. Full text screening, prioritization of publications about patients with a cancer diagnosis, and the addition of four citations identified during the hand search resulted in 72 final included publications, relating to 71 unique studies. This included 40 publications that described the time/resource use and/or costs associated with SC versus IV trastuzumab administration for the treatment of HER2-positive BC, and 28 publications that described time/resource use and/or costs associated with rituximab SC versus IV administration for the treatment of non-Hodgkin’s lymphoma/follicular lymphoma and diffuse large B-cell lymphoma. The majority of publications showed substantial time savings for preparation and administration of SC versus IV therapy, and cost savings associated with reductions in healthcare professional time and resource use for SC administration. Limitations There was a lack of consensus between publications regarding time and cost measurements. In addition, the search was limited to publications related to ...

Health technology assessments and value frameworks are becoming increasingly important for clinical decision-making. Most of these frameworks, however, focus on value to payers rather than patients and healthcare providers and may ignore other sources of economic value such as patient and physician time cost, impact on productivity, and direct health system costs. This article focusses on fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in the treatment of HER2-positive breast cancer. We review relevant clinical evidence, examine data on time and resource use of the subcutaneous administration of trastuzumab compared with intravenous treatment and how it can be extrapolated to PH FDC SC, and discuss the value PH FDC SC can bring to patients and healthcare providers. We will also provide our own experiences of PH FDC SC from the healthcare (oncologist, healthcare economist, pharmacist) and patient point of view. The data, combined with our personal experiences, suggest that switching from intravenous pertuzumab and trastuzumab to PH FDC SC could reduce non-drug costs for healthcare providers treating patients with HER2-positive breast cancer through time savings and other economic benefits. Furthermore, PH FDC SC could also save patient time given its shorter administration and post-injection observation time versus intravenous infusions, potentially resulting in reduced productivity loss. These benefits could be applied to other subcutaneous formulations, either currently available or in development.

544 Background: In patients with HER2-positive early breast cancer (BC), pertuzumab (P) added to trastuzumab (T) and chemotherapy has been recognized as a standard-of-care, improving the risk of recurrence. P and T treatments can be given intravenously (PT IV) or, more recently, subcutaneously − via PH FDC SC. Both methods are comparable in terms of efficacy and safety profiles. However, PH FDC SC allows for a faster infusion than that of PT IV, and this can be associated with lower costs. The aim of this study is to estimate the incremental difference in non-drug costs between PH FDC SC and PT IV for a typical patient receiving treatment for HER2-positive early BC in Western Europe and the United States. Methods: A model-based cost-minimization analysis was performed to quantify mean non-drug cost differences per patient over a full course of therapy (18 cycles). Western Europe: costs in the analysis are based on an archetypal country, and explicitly include estimates for costs for patient chair time, active healthcare professional (HCP) time, usage of non-drug consumables, port-a-cath placement surgeries and patients’ productivity losses. Costs are calculated by multiplying the resource use by its corresponding unit price. Costing data were obtained from literature sources on T SC time and cost savings for Western European countries, and assumptions on PH FDC SC and PT IV times and costs. United States: non-drug costs for the two strategies were estimated using average net reimbursement amounts for relevant procedure codes for intravenous and SC therapy administration among commercial payers in the MarketScan databases. Results: PH FDC SC is estimated to reduce non-drug costs by 73% − 80% in Western Europe, and 75% in the United States. Total monetary non-drug savings per patient over 18 cycles of treatment are estimated in the range of €2,474 − €8,975 in Western Europe, and at $10,138 in the United States. In Western Europe, where the analysis allows for a disaggregation by cost category, cost savings related to savings in patient chair time (excluding patients’ productivity losses) are estimated to account for up to 62% of overall non-drug cost savings. Patients’ productivity losses are estimated to explain up to 11% of non-drug cost differences. Conclusions: The use of PH FDC SC for the treatment of HER2-positive BC can potentially result in substantial non-drug cost savings. These savings could easily derive in overall net cost savings to the healthcare system, contributing to the long-term sustainability of the healthcare spending, while still providing a safe and effective therapy.[Table: see text]

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