key: cord-0764285-idxw2bhw
authors: Wang, Wei-Chun; Fann, Jean Ching-Yuan; Chang, Ray-E; Jeng, Ya-Chung; Hsu, Chen-Yang; Chen, Hsiu-Hsi; Liu, Jin-Tan; Yen, Amy Ming-Fang
title: Economic Evaluation for Mass Vaccination against COVID-19
date: 2021-05-25
journal: J Formos Med Assoc
DOI: 10.1016/j.jfma.2021.05.020
sha: 12d36437b13b0c48e35fd87096de317b8c5f08d6
doc_id: 764285
cord_uid: idxw2bhw

Background Vaccine is supposed to be the most effective means to prevent COVID-19 as it may not only save lives but also reduce productivity loss due to resuming pre-pandemic activities. Providing the results of economic evaluation for mass vaccination is paramount important for all stakeholders worldwide. Methods We developed a Markov decision tree for the economic evaluation of mass vaccination against COVID-19. The effectiveness of reducing outcomes after the administration of three COVID-19 vaccines (BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and AZD1222 (Oxford-AstraZeneca)) were modelled with empirical parameters obtained from literatures. The direct cost of vaccine and COVID-19 related medical cost, the indirect cost of productivity loss due to vaccine jabs and hospitalization, and the productivity loss were accumulated given different vaccination scenarios. We reported the incremental cost-utility ratio and benefit/cost (B/C) ratio of three vaccines compared to no vaccination with a probabilistic approach. Results Moderna and Pfizer vaccines won the greatest effectiveness among the three vaccines under consideration. After taking both direct and indirect costs into account, all of the three vaccines dominated no vaccination strategy. The results of B/C ratio show that one dollar invested in vaccine would have USD $13, USD $23, and USD $28 in return for Moderna, Pfizer, and AstraZeneca, respectively when health and education loss are considered. The corresponding figures taking value of the statistical life into account were USD $176, USD $300, and USD $443. Conclusion Mass vaccination against COVID-19 with three current available vaccines is cost-saving for gaining more lives and less cost incurred.

The outbreak of the novel Coronavirus disease 2019 (COVID- 19) since December 2019 has overwhelmed health systems around the world. It has claimed more than 2.7 million deaths as of the end of March 2021. 1 The high contagiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, has accumulated more than 125 million COVID-19 confirmed cases and forced authorities to issue strong containment measures, including stay home order, closure of stores, restaurants, schools and airports, lockdown of cities, and border quarantine in almost every country globally. In addition to the public health impact, the pandemic of COVID-19 also caused an enormous economic loss due to costly medical expenditure and loss of production capacity resulted from mitigation strategies. The total cost of the COVID-19 pandemic was estimated to be 90% annual gross domestic product in the US. 2 One-month lockdown in Tokyo would result in an 86% reduction of the daily production in Japan. 3 The development of novel vaccine against SARS-CoV-2 is anticipated to be the most useful tool to curb the rampage of the disease. As a matter of fact, the duration from the development of COVID-19 vaccines, the implementation of phase 1 to phase 4 randomized controlled trials, to the authority approval for market use is less than one year, even including the next-generation vaccine platforms for COVID-19, 4 much J o u r n a l P r e -p r o o f shorter than the traditional development of other vaccines, such as Ebola, polio, and influenza in history. 5, 6 As of the end of March 2021, there have been 13 vaccines approved, given the emergency use authorization issued by the Food and Drug Administration (FDA) in different countries. The UK is the first country to deploy a mass immunization campaign to the public, in which the first dose was delivered to a person on 8 th December 2020. Until now, >328 million subjects have received at least one dose in 158 countries. Among them, Israel takes the lead in vaccinations around the world. The epidemic curve of COVID-19 in Israel started to decline two weeks after the vaccination program launched on 20 th December 2020. 7 The more investment from government has been propagandized with an expected return of a global benefit of USD $17.4 trillion from an installation of capacity for 3 billion annual vaccine courses based on a vaccine market design. 8 Given the promising hope from vaccination, the cost-effectiveness would be of great interest to health decision-makers and governments worldwide. In addition to the incremental cost to save one additional person year widely used in cost-effectiveness analysis (CEA), one would like to know which factors and how much the magnitude these factors would influence the results of cost-effectiveness.

Besides cost-effectiveness analysis, it is also very interesting to report cost-benefit analysis (CBA) to answer the question of "how much benefit (e.g. monetary value) J o u r n a l P r e -p r o o f would be returned later given one unit price (dollar) spent in vaccine earlier?" with benefit (B)/Cost (C) ratio by considering direct and indirect cost form single payer viewpoint or societal viewpoint, respectively.

In this study, we aimed to develop a Markov decision model to evaluate the cost-effectiveness for COVID-19 vaccines. Take Israel as our role model, we simulated the epidemic curve since 1 st November 2020 when they had a resurge from the first wave of epidemic, implemented a vaccination program at day 51, and followed the cohort until day 180 with the built-in susceptible-infectious-recovery (abbreviated as SIR) model. The developed algorithm was also applied to the scenario if Israel would have not been administered with vaccination program ever. Compared with no vaccination strategy, the cost-effectiveness analysis was performed not only for the major brand of Israel's use, BNT162b2 (Pfizer-BioNTech) but also for two other major COVID-19 vaccines of mRNA-1273 (Moderna) and AZD1222 (Oxford-AstraZeneca) used worldwide. Factors relevant to the transmissibility of COVID-19, vaccination, and the disease-related medical expense in the sensitivity analyses would be tested for the robustness of the cost-effectiveness analyses. Finally, CBA was also performed to estimate B/C ratios for three vaccines. Figure 1 ). The compartment model of Susceptible (the "Susceptible" node)-Infected (the shaded square marked by "Infected")-Recovery (the "Recovery" node) (abbreviated as SIR) was used for depicting the dynamic of COVID-19 transmission in community. 9, 10 For the prevention strategy with vaccination program, susceptible subjects will be moved to the vaccinated group (the "Vaccinated subjects" node) according to the vaccination schedule. The vaccinated subjects follow the same structure of SIR and disease progression but with lower risks of being infected, depending on the efficacy of vaccine under consideration.

Extended from the conventional SIR model, subjects being infected by SARS-CoV-2 can be symptomatic or asymptomatic with the asymptomatic proportion of 17%. 11 Regarding the symptomatic COVID-19 cases, some of them would be recovered after a period of self-isolation (the node of "Isolation at home"), whereas 15% of these subjects were required to be treated with hospitalization, which was J o u r n a l P r e -p r o o f estimated from the reported data in Italy by using a Queue model with the methods detailed in this special issue. 12 For the hospitalized COVID-19 patients, we applied a COVID-19 clinical evolution model detailed as follows. Table 1 shows the values of daily transition probabilities from three disease states.

Note that the high risk state corresponds to the medical need for intensive care unit (ICU) management and the low and medium risk states require ward care J o u r n a l P r e -p r o o f equipped with negative pressure facility. As the disease progresse to medium risk state the use of non-invasive ventilator is required.

To take into account the uncertainty inherited from the evolution of COVID-19 in terms of the proportions of asymptomatic cases and hospitalization needs and the daily probabilities of disease progression after being admitted to hospital, a probabilistic approach was adopted. For the asymptomatic proportion, the Beta distribution of Beta(111, 552) was used ( Table 1) . Regarding the daily transition rates of hospitalized COVID-19 patients across five disease states, a Dirichlet distribution with the marginal summation of 1000 was adopted.

The parameters on the effectiveness of vaccination in preventing asymptomatic and symptomatic COVID-19 cases were derived from the published literatures of phase 3 clinical trials including the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and AZD1222 (Oxford-AstraZeneca). [16] [17] [18] Information on the point and interval estimates of vaccine efficacy of symptomatic and asymptomatic cases was abstracted. The prevalence of adverse effects of fever or more severe was borrowed from the findings in the phase 4 post-market reports and was incorporated into the cost-effectiveness analysis by using Beta distributions. In the current analysis, we J o u r n a l P r e -p r o o f assumed no vaccine jab would be required once 70% of population was vaccinated or infected with COVID-19.

In the current cost-effectiveness analysis, both healthcare payer and societal perspectives were adopted. The direct cost associated with the prevention and treatment for COVID-19 cases was considered. It includes the cost for testing using RT-PCR for the identification of infected cases. For the prevention strategy with vaccination, the cost for vaccination and its administration were considered. 19 The aggregated cost for hospitalized COVID-19 patients including caring in the facility of isolation ward, supportive care, and oxygenation for the low, medium, and high risk patients was used. For patients in medium risk state, the cost for using non-invasive positive pressure ventilation was included. Regarding the patients in high risk state, the aggregated cost for the management of patients in the facility of ICU with the precaution for infection control and the use of invasive ventilator or ECMO was used.

For the high risk patients, the cost for using computed tomography to evaluate the severity of pulmonary lesions was also applied. Information on the cost was collected from the National Health Insurance Administration, Taiwan. 20 Triangular distributions were used for costs to account for the uncertainties of relevant costs.

We considered the indirect cost pertaining to productivity loss due to COVID-19 related hospitalization, half-day course for vaccine jab, and two-day sick leave if there was adverse effect from vaccination. The unit of one-day productivity loss was calculated based on the expected GDP per capital in Taiwan 

For the economic evaluation, we borrowed the scenario in Israel for our simulation. The cohort size was 8,362,864. The initial condition of 11,016 COVID-19 cases on Nov 1, 2020, the date when the second surge of epidemic was about to rebound after a well-controlled period, was applied. Vaccine of SARS-CoV-2 was administered since day 51. In the initial 15 days, the daily vaccine jabs were 40,000. It increased to 80,000 afterwards.

A constellation of COVID-19 related outcomes were collected, including numbers of asymptomatic and symptomatic infectives, days of hospitalization, number of death, and the quality adjusted life days (QALDs) gained in the simulated cohort with and without vaccination administered. The QALDs of low, medium, and high risk COVID-19 was set as a previous study did. 21 We used one-day for a Markov cycle. The time horizon in this analysis was 180 days. As this is a short period, neither cost nor utility was discounted in the current analysis. The incremental cost-utility ratio (ICUR) for cost per QALD gained was calculated as the difference of cost for different vaccines versus no vaccine strategy divided by the QALD gained from the vaccination program.

We performed the cost-benefit analysis for the COVID-19 vaccines with benefit-cost ratio (BCR) of four approaches. The first one (BCR1) was from the payer's perspective with BC ratio calculated as saving on COVID-19 related medical cost divided by the direct cost of vaccine. The second one (BCR2) was from societal perspective with BC ratio calculated as saving on the direct cost of medical expenditure and the indirect cost divided by the direct cost of vaccine. The latter two are from macro viewpoint to consider the economic impacts due to productivity and 

The one-way sensitivity analyses were applied to examining the robustness of Table 1) . For each parameter sample, the microsimulation was conducted with 10,000 first-order simulation trials. An incremental cost-utility scatter plot was depicted to determine the spread of the ICURs. 28 The authors reported the uniformly cost-effectiveness of vaccination strategies for hospitalized COVID-19 patients using the willingness-to-pay threshold of USD 50,000. They found that the effectiveness of mass vaccination strategy in more than 50% reduction for hospitalization days and mortality with the reduction of health cost by 90%. The probability of being cost-effective for mass vaccination strategy was around 70% given the wiliness-to-pay threshold of USD $50,000.

In addition to strengthen the evidence of cost-effectiveness in vaccination Secondly, the serious adverse events of vaccination such as thrombosis and anaphylactic reactions were not included in the current evaluation due to the rarity of these events and the uncertainty in the evaluation. 29, 30 With the wide-spread rolling out of vaccination and the continuous monitoring of adverse events at global scale, this impact can be incorporated in the further study. Thirdly, considering the rapid evolution on the pandemic, the time frame in the current analysis was set at 180 days. This is also the durability of the immunity conferred by the available vaccines.

However, the uncertainty about the duration of immunity needs more researches to support. The fourth limitation is that our current CUA or CBA analysis have not taken into account vaccine hesitancy, which may disfavor the results of CEA and CBA. This In conclusion, mass vaccination against COVID-19 with three current available vaccines is cost-saving for gaining more lives and less costs incurred. These findings provide the evidence for informed decision making and all stakeholders for the discovery, production, and delivery of COVID-19 vaccine.

J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f 

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