Should rapid antigen tests be government funded in Australia? An economic evaluation

Objective: Easy and equitable access to testing is a cornerstone of the public health response to COVID-19. Currently in Australia, testing using Polymerase Chain Reaction (PCR) tests for COVID-19 is free-to-the-user, but the public purchase their own Rapid Antigen Tests (RATs). We conduct an economic analysis of government-funded RATs in Australia. Design: An interactive decision tree model was developed to compare one policy in which government-funded RATs are free-to-the-user, and one in which individuals purchase their own RATs. The decision tree represents RAT and PCR testing pathways for a cohort of individuals without COVID-19-like symptoms, to estimate the likelihood of COVID-19 positive individuals isolating prior to developing symptoms and the associated costs of testing, from a government perspective. Data sources: Test costs and detection rates were informed by published studies, other input parameter values are unobservable and uncertain, for which a range of scenario analyses are presented. Data synthesis: Assuming 10% prevalence of COVID-19 in a cohort of 10,000 individuals who would use government-funded RATs, the model estimates an additional 464 individuals would isolate early at a cost to the government of around $52,000. Scenario analyses indicate that the incremental cost per additional COVID-19 positive individual isolating with no symptoms remains at a few hundred dollars at 5% prevalence, rising to $2,052 at 1% prevalence. Conclusions: Based on the presented decision tree model, even only minor reductions in COVID-19 transmission rates due to early isolation would justify the additional costs associated with a policy of government-funded RATs.

MH370 Controlled Eastward Veering and Descent After the 6th Arc

Past expert analyses of communication signals from missing Malaysian Airlines MH370 reconciled Burst Frequency Offset (BFO) errors up to the 6th of 7 arcs for a southerly track. After the 6th arc, the Satellite Data Unit (SDU) power-up or reboot resulted in settling errors in the last two data points that were ignored (first search) and later bounded (second search). For the second search, investigators invoked a high-speed vertical descent to account for BFO errors for the south track fuel-starved scenario. Two searches disappointingly failed to find the implied violent-crash site. We report that interpretations were flawed in suggesting the plane dived vertically, as investigators did not recognize that BFO extrapolations implicitly implied mathematically that the plane was also cruising along the south track, but with no fuel. Our reanalysis used the “Penang Longitude” (PL) theory that predicted a similar southerly track to the 6th arc, and that MH370 subsequently veered eastwards and descended. Doppler Shifts from vertical motions were replaced with plausible horizontal veering and declination of a high-speed aircraft. Veering predicted by the PL theory plus controlled descent plausibly accounts for nominal 7th arc BFO discrepancies for the warm-reboot scenario. We conclude that the fuel-starvation scenario analyses wrongly implied a vertical high-speed crash that ignored the impossible implicit southerly cruise, with no fuel, assumption. Instead, MH370 was piloted to a precise glide landing under power, east of the 7th arc.

Analyzing the Contribution of Human Mobility to Changes in Air Pollutants: Insights from the COVID-19 Lockdown in Wuhan

During the COVID-19 lockdown in Wuhan, transportation, industrial production and other human activities declined significantly, as did the NO2 concentration. In order to assess the relative contributions of different factors to reductions in air pollutants, we implemented sensitivity experiments by Random Forest (RF) models, with the comparison of the contributions of meteorological conditions, human mobility, and emissions from industry and households between different periods. In addition, we conducted scenario analyses to suggest an appropriate limit for control of human mobility. Different mechanisms for air pollutants were shown in the pre-pandemic, pre-lockdown, lockdown, and post-pandemic periods. Wind speed and the Within-city Migration index, representing intra-city mobility intensity, were excluded from stepwise multiple linear models in the pre-lockdown and lockdown periods. The results of sensitivity experiments show that, in the COVID-19 lockdown period, 73.3% of the reduction can be attributed to decreased human mobility. In the post-pandemic period, meteorological conditions control about 42.2% of the decrease, and emissions from industry and households control 40.0%, while human mobility only contributes 17.8%. The results of the scenario analysis suggest that the priority of restriction should be given to human mobility within the city than other kinds of human mobility. The reduction in the NO2 concentration tends to be smaller when human mobility within the city decreases by more than 70%. A limit of less than 40% on the control of the human mobility can achieve a better effect, especially in cities with severe traffic pollution.

Evaluation of Nutri-Score in Relation to Dietary Guidelines and Food Reformulation in The Netherlands

An unhealthy dietary pattern is an important risk factor for non-communicable diseases. Front-of-Pack nutritional labels such as Nutri-Score can be used to improve food choices. In addition, products can be improved through reformulation. The current study investigates to what extent Nutri-Score aligns with the Dutch Health Council dietary guidelines and whether it can be used as an incentive for reformulation. Nutri-Score calculations were based on the Dutch Branded Food database (2018). The potential shift in Nutri-Score was calculated with product improvement scenarios. The Nutri-Score classification is in line with these dietary guidelines: increase the consumption of fruit and vegetables, pulses, and unsalted nuts. It is, however, less in line with the recommendations to limit (dairy) drinks with added sugar, reduce the consumption of red meat and replace refined cereal products with whole-grain products. The scenario analyses indicated that a reduction in sodium, saturated fat or sugars resulted in a more favourable Nutri-Score in a large variety of food groups. However, the percentage of products with an improved Nutri-Score varied greatly between the different food groups. Alterations to the algorithm may strengthen Nutri-Score in order to help consumers with their food choices.

Cost-Effectiveness of Nivolumab Plus Cabozantinib Versus Sunitinib as a First-Line Treatment for Advanced Renal Cell Carcinoma in the United States

Background: In a recent randomized, phase 3 trial (CheckMate 9ER), nivolumab combined with cabozantinib significantly improved patient outcomes compared with sunitinib. However, the cost-effectiveness of these novel agents for untreated advanced renal cell carcinoma (aRCC) remains unknown.Materials and Methods: We constructed a microsimulation decision-analytic model to measure the healthcare costs and outcomes of nivolumab plus cabozantinib compared with those of sunitinib for patients with aRCC. The transition probability of patients was calculated from CheckMate 9ER using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated for nivolumab-plus-cabozantinib treatment compared with sunitinib from a US payer perspective. We conducted one-way and probabilistic sensitivity analyses and a series of scenario analyses to evaluate model uncertainty.Results: Nivolumab plus cabozantinib was associated with an improvement of 0.59 LYs and 0.56 QALYs compared with sunitinib. However, incorporating nivolumab plus cabozantinib into first-line treatment was associated with significantly higher lifetime costs ($483,352.70 vs. $198,320.10), causing the incremental cost-effectiveness ratio for nivolumab plus cabozantinib to be $508,987/QALY. The patients’ age of treatment, first-line utility, and cost of nivolumab had the greatest influence on the model. The outcomes were robust when tested in sensitivity and scenario analyses.Conclusion: For aRCC, substituting nivolumab plus cabozantinib in the first-line setting is unlikely to be cost-effective under the current willingness-to-pay threshold ($150,000/QALY). Significant price decreases for nivolumab used in first-line therapy would be needed to drop ICERs to a more diffusely acceptable value.

Calibration and Validation of AQUACROP and APSIM Models to Optimize Wheat Yield and Water Saving in Arid Regions

The APSIM-Wheat and AQUACROP models were calibrated for the Sakha 95 cultivar using phenological data, grain and biomass yield, and genetic parameters based on field observation. Various treatments of planting dates, irrigation, and fertilization were applied over the two successive winter growing seasons of 2019/2020 and 2020/2021. Both models simulated anthesis, maturity dates, grain yield, and aboveground biomass accurately with high performances (coefficient of determination, index of agreement greater than 0.8, and lower values of root mean square deviation) in most cases. The calibrated models were then employed to explore wheat yield and water productivity (WP) in response to irrigation and nitrogen fertilization applications. Scenario analyses indicated that water productivity and yield of wheat ranged from 1.2–2.0 kg m–3 and 6.8–8.7 t ha–1, respectively. Application of 0.8 from actual evapotranspiration and 120% from recommended nitrogen dose was the best-predicted scenario achieving the highest value of crop WP. Investigating the suitable option achieving the current wheat yield by farmers (7.4 t ha–1), models demonstrated that application of 1.4 from actual evapotranspiration with 80% of the recommended nitrogen dose was the best option to achieve this yield. At this point, predicted WP was low and recorded 1.5 kg m–3. Quantifying wheat yield in all districts of the studied area was also predicted using both models. APSIM-Wheat and AQUACROP can be used to drive the best management strategies in terms of N fertilizer and water regime for wheat under Egyptian conditions.

Reducing carbon footprint of inhalers: analysis of climate and clinical implications of different scenarios in five European countries

BackgroundInhaled therapies are key components of asthma and chronic obstructive pulmonary disease (COPD) treatments. Although the use of pressurised metered-dose inhalers (pMDIs) accounts for <0.1% of global greenhouse gas emissions, their contribution to global warming has been debated and efforts are underway to reduce the carbon footprint of pMDIs. Our aim was to establish the extent to which different scenarios led to reductions in greenhouse gas emissions associated with inhaler use, and their clinical implications.MethodsWe conducted a series of scenario analyses using asthma and COPD inhaler usage data from 2019 to model carbon dioxide equivalent (CO2e) emissions reductions over a 10-year period (2020–2030) in the UK, Italy, France, Germany and Spain: switching propellant-driven pMDIs for propellant-free dry-powder inhalers (DPIs)/soft mist inhalers (SMIs); transitioning to low global warming potential (GWP) propellant (hydrofluoroalkane (HFA)-152a) pMDIs; reducing short-acting β2-agonist (SABA) use; and inhaler recycling.ResultsTransition to low-GWP pMDIs and forced switching to DPI/SMIs (excluding SABA inhalers) would reduce annual CO2e emissions by 68%–84% and 64%–71%, respectively, but with different clinical implications. Emission reductions would be greatest (82%–89%) with transition of both maintenance and SABA inhalers to low-GWP propellant. Only minimising SABA inhaler use would reduce CO2e emissions by 17%–48%. Although significant greenhouse gas emission reductions would be achieved with high rates of end-of-life recycling (81%–87% of the inhalers), transition to a low-GWP propellant would still result in greater reductions.ConclusionsWhile the absolute contribution of pMDIs to global warming is very small, substantial reductions in the carbon footprint of pMDIs can be achieved with transition to low-GWP propellant (HFA-152a) inhalers. This approach outperforms the substitution of pMDIs with DPI/SMIs while preserving patient access and choice, which are essential for optimising treatment and outcomes. These findings require confirmation in independent studies.

Cost-Effectiveness of Apomorphine Sublingual Film as an "On-Demand" Treatment for "OFF" Episodes in Patients with Parkinson's Disease

Background: “On-demand” treatments approved in the United States (US) for “OFF” episodes in Parkinson’s disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing “OFF” episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments’ pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without “OFF” episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per “OFF” hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total “on-demand” treatment costs ($42,095) compared with SC-APO ($276,320; difference: –$234,225) and CVT-301 ($69,577; difference: –$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per “OFF” hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and adverse event–related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of “OFF” episodes in patients with PD.

12. Modeled Impact of the COVID-19 Pandemic and Associated Reduced Adult Vaccinations on Herpes Zoster in the United States

Background During the COVID-19 pandemic, adult vaccination in the United States (US) decreased substantially in 2020. Unlike other vaccine-preventable diseases where individuals may have experienced reduced risk due to COVID-related mitigation efforts (e.g., lockdown restrictions, use of face masks), individuals remained at risk of herpes zoster (HZ). This study projects the impact of reduced recombinant zoster vaccine (RZV) use on HZ cases and complications in the US. Methods A multi-cohort Markov model estimated the impact of missed RZV vaccinations, by comparing scenarios with and without missed vaccinations between Apr-Dec 2020, on cases of HZ, postherpetic neuralgia (PHN), and quality-adjusted life-years (QALYs) among US adults aged ≥ 50 years. Epidemiology, RZV efficacy, and utility inputs were obtained from standard US sources, clinical trial data, and published literature. Missed doses were estimated using data on RZV doses and an assumed 43% reduction in RZV vaccinations during the pandemic, based on publicly available data. Deterministic sensitivity and scenario analyses were conducted. Results In 2020, approximately 21 million (M) RZV distributed doses were expected, including an estimated 9.2M RZV series initiations in Apr-Dec. An estimated 3.9M RZV series initiations were missed, resulting in 31,945 projected HZ cases, 2,714 PHN cases, and 610 lost QALYs projected over a 1-year follow up. If individuals with missed RZV initiations remain unvaccinated in 2021, avoidable HZ cases will increase to 63,117 over 2 years. Further, if the same number of RZV initiations are missed in 2021, 95,062 avoidable HZ cases are expected. In a sensitivity analysis assuming 30% RZV reduction, 18,020 avoidable HZ cases and 1,531 PHN cases were observed over 1 year. Conclusion Adding to the substantial COVID-19 infection-related morbidity and mortality, reduced RZV use during the pandemic resulted in further burden from avoidable HZ cases. Health care providers should continue to emphasize the importance of vaccination against HZ and other preventable diseases during the pandemic. Funding GlaxoSmithKline Biologicals SA (GSK study identifier: [VEO-000222]). Acknowledgement Business & Decision Life Sciences c/o GSK (Coordination: Quentin Rayée). Disclosures Elizabeth M. La, PhD, The GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder) Ahmed Salem, MSc, The GSK group of companies (Employee) David Singer, PharmD, MS, The GSK group of companies (Employee) Nicolas Lecrenier, Ing, PhD, The GSK group of companies (Employee, Shareholder) Sara Poston, PharmD, The GSK group of companies (Employee, Shareholder)