Among the number of cost-effectiveness ratios generated, one of the most interesting results suggests that interventions such as screening, border control or individual measures would not be cost-effective measures when implemented separately, particularly in severe scenarios of pandemics. However, considering that no other mitigation measures are available to date, even if such strategies would not be cost-effective, fever screening, border control and individual measures have been widely implemented during the major COVID-19 events in Italy in early 2020. The main explanations are that not only the cost-effectiveness assessments of these public health measures were not available at that time to assist decision-making, but also, the economic impacts and economic arbitrations were not the priority of policy makers given the urgency of this new pandemic.
Another interesting result concerns the good cost-effectiveness ratios based on mortality outcomes of the implementation of new life support equipment (such as ventilators and ECMO). Since its use in the 1950s in operating rooms, life support equipment is becoming a promising rescue strategy for cardiopulmonary arrest in ICU. With expanding potential indications to acute respiratory distress syndrome in the frame of severe influenza (or COVID-19), there is significant interest in the early application of life support equipment in the Emergency Departments during pandemics.[29]
The A/H1N1pdm09 pandemic brought life support equipment technology into the light with excellent results of reducing mortality caused by respiratory distress, which would explain the favorable ACER. These results are quite robust because of the wide distribution range of potential costs of implementing such equipment as assessed in the Monte Carlo simulations (between 0.1 and 1.13 M€ for pandemic scenarios types A-B-C, between 8.46 and 335.67 M€ for epidemic scenarios D-E and between 58.66 and 2343.75 M€ for major event epidemic scenario D) (Table 4). In addition, the same results could be applied for the Covid-19 pandemic.
These economic estimates regarding life support equipment versus other interventions should contribute to deploying the necessary life support material in the Italian national territories in a timely manner. Interestingly, this equipment could be also used to treat a growing number of other potential indications such as acute hypoxemic respiratory failure, cardiac arrest or cardiogenic shock related to this new pandemic. Continuing research in Public Health mitigation and containment measures for pandemics including economic evaluations will likely spur further expansion of life support equipment during influenza pandemics.[30]
Comparing eight different public health interventions has been possible by selecting common and meaningful effectiveness outcomes based on morbidity and mortality reductions suitable to each intervention. Comparisons of such different public health interventions against pandemics is not commonly undertaken for several reasons: the lack of comparative studies of public health measures, the cultural variability about preventive strategies, the lack of international consensus on optimal strategies to consider, the epidemiological conditions for switching to an alternative measure, and the precise switching strategy in case of insufficient response to a previous intervention.
The feasibility of such studies is also questioned because conducting comparative studies with potential suboptimal prevention strategies would likely raise ethical issues during a major outbreak. Furthermore the prohibitive cost of conducting multi-arm trials to assess and compare a combination of various public health interventions used concurrently and/or in a sequential manner make such an experiment totally impractical. One alternative includes conducting simulations using advanced modelling approaches, as carried out in the frame of the FLURESP project.[4, 31].
The COVID global pandemic now has the specificity of having experimented a wide range of public health measures. Then further cost-effectiveness studies should take into account the long term health impact, such as health losses and costs associated with untreated chronic conditions, as well as the broader socio-economic impact, including mental health and lost productivity.[8, 32, 33].
Importantly, many published “cost-effectiveness” analyses used the synthetic indicator “Quality Adjusted Life Years” (QALY) as a standard outcome for comparing interventions.[34–36]. This approach assesses utility measures of patient preferences calibrated between 0 (death) and 1 (full health). Technically entitled "Cost-Utility Analyses" this outcome is subject of an active methodological controversy in health economics. Both the scientific community and decision makers must be aware of this methodological debate in order to better understand why numerous publications present cost-utility analyses expressed in "costs per QALY" under the umbrella of “cost-effectiveness” analyses without distinguishing that they consist in fact of two different methods, which are not equivalent, and not interchangeable.
The fact that effectiveness criteria based on morbidity and mortality reduction selected for this project are clinically meaningful and relevant to all kinds of interventions is a major contribution for decision-making purposes. Selecting objective and consistent public health outcomes allows the performance of a given intervention to be assessed and expressed more accurately and compared across different strategies within various population groups. It is the reason why this study used a public-health-meaningful outcome such as "success rate" (achieving a mortality reduction of 40%) leading to cost-effectiveness ratios expressed in "costs per success". Of course, the selected thresholds of 40% reduction could be challenged, but could also be changed and adapted according to health authorities’ priorities. Another potential limitation of these results is that performance effectiveness values have been derived from published data concerning the French Health System.[4]. Total costs and performance of public health interventions from country to country are rarely published in a consistent way, requiring specific surveys to be carried out in each target country. For example, basic epidemiological indicators such as morbidity and mortality indicators are collected and recorded differently among countries.
An additional limitation is that reported cost-effectiveness ratios present only direct costs. Indirect costs (lost productivity, absenteeism, etc.) appear to be important factors to consider in public health interventions against pandemics[37]. But again, the lack of standardization and high variability of indirect costs make international comparisons difficult.
Similar results have been generated in three other health systems in the frame of the European Commission project, namely France[4], Romania and Poland, confirming that there would be a good chance that most cost-effective public health measures in one European country would also be cost-effective in other European countries. As for any economic evaluation studies however, precise national results should be generated from a robust dedicated data collection carried out in the relevant health systems.
Furthermore, national data are also sensitive with time and such economic evaluation of public health interventions should be organized on a regular basis, ideally after each pandemic.
In conclusion, because various public health measures implemented during human influenza pandemics and the COVID-19 pandemic in Italy are practically the same, the results generated originally to assess interventions against various scenarios of influenza pandemics appear potentially relevant to any other respiratory viruses pandemics in general, including the COVID-19 pandemic. However novel public health measures have been experimented for the first time during the COVID-19 pandemic, such as lock down, curfews and vaccination passports. As these new measures were not included in any existing preparedness plans against Human influenza pandemic, they have not been assessed in the frame of the FLURESP project which then is unable to provide any information about the costs and performance of such measures.
The main implications of the FLURESP initiative are the following:
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The methodology confirms that it is possible to compare various interventions (therapeutic or non-therapeutic), using common and meaningful public health criteria
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The FLURESP project provides a framework for assessing public health measures, considering that most of public health interventions implemented during the COVID-19 pandemic have not been previously evaluated in term of costs and effectiveness
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The results led to guidelines for reducing pandemic mortality by ranking public measures by level of cost-effectiveness.