NTEGRATION OF LOGISTICS SYSTEMS OF DEVELOPING COUNTRIES INTO INTERNATIONAL LOGISTICS CHANNELS

Modern logistics significantly influences the globalization and internationalization processes. Logistics systems are becoming increasingly important in today’s rapidly changing environment. The aim of the article was to investigate the national logistics systems of developing countries in the context of their integration capabilities. The main methods used in this study are statistical analysis, index, graphical and analytical methods, methods for estimating structural dynamic shifts, comparisons. Commonly used methods of economic research, as well as statistical analysis and interstate comparisons, economic modelling (trend analysis to determine the forecast level of LPI for Ukraine), etc. were also involved. The logistics environment of Poland, Bulgaria, India and Ukraine, as well as the factors of its formation are evaluated. The components of the logistic portrait of the country in the context of integration capabilities of the logistic system are offered. It was found for the studied countries that the destimulator of the national logistics system is infrastructure (for Poland), infrastructure and customs (for Bulgaria and Ukraine), customs (for India). It is these components that need priority attention in the context of increasing the integration capabilities of logistics systems, because the results indicate that they lag far behind international standards. Prospects for further research involve studies of the impact of pandemics, globalization, digitalization on logistics systems, including that of developing countries.

Accelerating manufacturing to start large-scale supply of a new adenovirus-vectored vaccine within 100 days

The Coalition for Epidemic Preparedness Innovations &rsquo &lsquo 100-day moonshot &rsquo aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing the output from the available manufacturing footprint. We describe a rapid viral seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a new perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by around four-fold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10000 doses from each liter of bioreactor capacity. Transition to a new production process across a large manufacturing network is a major task. In the short term, the rapid seed generation workflow could be used with the existing production process. We also use techno-economic modelling to show that, if linear scale-up were achieved, a single cleanroom containing two 2000 L bioreactors running our new perfusion-based process could supply bulk drug substance for around 120 million doses each month, costing <0.20 EUR/dose. We estimate that a manufacturing network with 32000 L of bioreactor capacity could release around 1 billion doses of a new vaccine within 130 days of genomic sequencing of a new pathogen, in a hypothetical surge campaign with suitable prior preparation and resources, including adequate fill-and-finish capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.

OP443 Evaluating The Value Of Endovascular Innovations For Aortic Valve Replacement Through Clinical Benefits, Patient-reported Outcomes And Resource Consumption.

IntroductionThe use of most recent Transcatheter aortic valve implants (TAVI) in the treatment of symptomatic severe aortic stenosis (SAS) is evolving with expanded indications from inoperable/high-risk to intermediate and low risk patients. Consequently, TAVI outcomes must be monitored to highlight its value under real-world conditions. Our aim was to prospectively evaluate TAVI (SAPIEN 3) outcomes in terms of patient's health-related quality of life (HRQoL), clinical outcomes, and healthcare resource utilization (HRU).MethodsAn observational prospective study including all consecutive patients with SAS undergoing a transcatheter valve implantation with Edwards SAPIEN 3 valve (transfemoral access) was conducted in full accordance with clinical guidelines from the European Society of Cardiology. Patients were evaluated before the intervention (baseline), at discharge, and after one, six and twelve months from the implant. A thoughtful and systematic evaluation of patients’ HRQoL (EQ-5D 5L, the Short Form-36 Health Survey -SF-36- and the Kansas City Cardiomyopathy Questionnaire -KCCQ-), clinical endpoints (that is, cardiovascular mortality, and rates of stroke, major bleeding, myocardial infarction, and re-hospitalization), echocardiographic measurements, and HRU (that is, Length of stay-LOS- in ward/intensive care unit -ICU-) was implemented. Multivariate regression models were applied to test outcomes while controlling key risk factors (that is, patient’ severity at baseline).ResultsA total of seventy-six patients (fifty percent female, fifty-five percent of intermediate-high risk) with a mean age of 82.1 ± 4.78 years were included. Implant success was 97.34% and cardiovascular death was 2.6% at one year. Significant reductions in mean and maximum gradients were achieved and maintained during follow-up. Mean LOS in ward (5.2 ± 4.0days) and ICU (0.22 ± 0.64 days) were low. Statistically significant improvements were detected in the KCCQ overall summary scores, EQ-5D, and SF-36 (Physical component summary) - all adjusted - p < 0.05 - after the intervention.ConclusionsTAVI represents a safe and effective innovation for SAS with clinical benefits translated into significant improvements in terms of HRQoL. Besides, the low HRU provides new insights for health-economic modelling and the optimization of limited resources of special importance under current pandemic situation.

Improving the understanding of how patients with non-dystrophic myotonia are selected for myotonia treatment with mexiletine (NaMuscla): outcomes of treatment impact using a European Delphi panel

Background Non-dystrophic myotonias (NDMs) comprise muscle chloride and sodium channelopathies due to genetic defects of the CLCN1- and SCN4A-channels. No licensed antimyotonic treatment has been available until approval of mexiletine (NaMuscla®) for adult patients by the EMA in December 2018. This Delphi panel aimed to understand how outcomes of the pivotal phase III Mexiletine study (MYOMEX) translate to real world practice and investigate health resource use, quality of life and the natural history of NDM to support economic modelling and facilitate patient access. Methods Nine clinical experts in treating NDM took part in a two-round Delphi panel. Their knowledge of NDM and previous use of mexiletine as an off-label treatment prior to NaMuscla’s approval ensured they could provide both qualitative context and quantitative estimates to support economic modelling comparing mexiletine (NaMuscla) to best supportive care. Consensus in four key areas was sought: healthcare resource utilization (HRU), treatment with mexiletine (NaMuscla), patient quality of life (QoL), and the natural history of disease. Concept questions were also asked, considering perceptions on the feasibility of mapping the validated Individualized Neuromuscular Quality of Life (INQoL) instrument to the generic EQ-5D™, and the potential impact on caregiver QoL. Results Consensus was achieved for key questions including the average long-term dosage of mexiletine (NaMuscla) in practice, the criteria for eligibility of myotonia treatment, the clinical importance of QoL outcomes in MYOMEX, the higher proportion of patients with increased QoL, and the reduction in the need for mental health resources for patients receiving mexiletine (NaMuscla). While consensus was not achieved for other questions, the results demonstrated that most experts felt mexiletine (NaMuscla) reduced the need for HRU and was expected to improve QoL. The QoL mapping exercise suggested that it is feasible to map domains of INQoL to EQ-5D. Points of interest for future research were identified, including that mexiletine (NaMuscla) may slow the annual decrease in QoL of patients over their lifetime, and a significant negative impact on QoL for some caregivers. Conclusions This project successfully provided data from an informed group of clinical experts, complementing the currently available clinical trial data for mexiletine (NaMuscla) to support patient access decisions.

PP275 Incorporating Quality-Of-Care Indicators In Health Economic Modelling: A Case-Study On Surgical Site Infections In Cardiac Surgery

IntroductionSurgical site infections (SSIs) are preventable adverse events placing a large burden on service providers. Reusable electrocardiogram lead-and-wire systems can hold infection vectors after cleaning. Single-patient-use cable-and-lead systems (spECG) may help prevent cross-contamination and SSIs. SSIs are commonly included in incentive schemes as quality-of-care indicators. Readmissions within 30 days due to SSI are not reimbursed by the UK's National Health Service (NHS). Reducing SSIs could improve patient care and result in cost-of-care savings. The cost-benefit of implementing spECG was investigated in this study.MethodsNHS Digital 2019 data for cardiac surgeries were assessed for SSIs occurring during the index event or 90 days post discharge. Data from 88 centers performing 1,000 surgeries or more were used to update a published health economic model of the cardiac surgery care pathway. The population was on average 68 years old, 18 percent female, 33 percent obese, and 28 percent diabetic. Costs are reported in 2019 GBP (2019 EUR) and were sourced from NHS reports.ResultsIn total, 2,580 in-hospital SSIs were reported from 317,825 cardiac surgeries, resulting in an increased length-of-stay (LOS) of between 4.4 to 29.4 days. The 1,975 SSI-related, post-discharge readmissions’ mean LOS was 13.9 days. Cost-of-care was GBP8,127 (EUR9,259) per patient, in line with NHS data. Implementing spECG reduced per-case-costs to GBP8,094 (EUR9,221), saving GBP33 (EUR38): a 3.5-fold return-on-investment. Savings-drivers were fewer SSIs, reduced LOS, and fewer readmissions (a reduction of 29% within 30-days, resulting in cost-offsets of approximately GBP230 (EUR262)/readmission).ConclusionsThis study suggests that the implementation of spECG could provide cost-benefit in reducing the burden of SSIs related to cardiac surgery. In addition to cost-of-care, the readmissions would have additionally burdened hospitals, as 29 percent would not have been reimbursed. Health-economic analyses should consider not only potential cost-savings of innovative products, but also incorporate quality-of-care indicators. This further aligns payer considerations with the common end-goal of providing maximum benefit to patients.

Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review

Background How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes. Methods We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed. Results The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage. Conclusion The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.