Overview

Figure presents the final attack rate (AR) and the total cost of the epidemic for each intervention strategy applied, for a pandemic with a basic reproduction number of R

_{0}=

1.8. Although costs are calculated from the whole-of-society perspective, total costs are presented as a cost per person in the community, calculated by dividing the simulated cost of the pandemic by the population of ~30,000, in order to make the results more easily transferable to communities of various sizes. Strategies are ordered from left to right by increasing effectiveness (i.e. their ability to decrease the attack rate), and only intervention strategies that reduce the attack rate by at least 50% are included.

Figure shows three distinctive features. Firstly, for an epidemic with basic reproduction number R

_{0}=

1.8, no single intervention is effective in reducing the attack rate by more than 50%, and thus do not appear in Figure . This finding is consistent with previous modelling studies which found that layering of multiple interventions is necessary to achieve substantial attack rate reductions [

5-

10,

12,

57,

58]. Secondly, higher severity pandemics have higher total costs. Total costs of unmitigated pandemics range from $441 to $8550 per person for pandemics from category 1 to category 5 (see Table ). Thirdly, for high severity pandemics total costs are lower for the more effective intervention strategies.

Figure presents the constituent components that make up the total cost of each intervention and severity category, measured in terms of cost per person in the modelled community. Three distinctive features can be seen in Figure . Firstly, for high severity pandemics costs are dominated by productivity losses due to death and health care costs. Secondly, for low severity pandemics costs are dominated by social distancing and illness costs. Thirdly, for all severity categories antiviral costs are comparatively low when compared with all other cost components of antiviral based intervention strategies. Antiviral costs never constitute more than 20% of the total cost, and for all severity categories greater than 1 (CFR >0.1%) antiviral costs are always the smallest cost component.

Below we report on effectiveness, total costs and cost components of interventions for pandemics with high and low severity. These cost data are presented in Table .

High severity pandemics

Figure summarises the characteristics of key intervention strategies. For high severity pandemics (categories 4 and 5, with case fatality rates above 1.5%) the least costly strategy combines continuous school closure, community contact reduction, antiviral treatment and antiviral prophylaxis. At category 5 this strategy has a total cost of $1,584 per person, a net benefit of $6996 per person compared to no intervention. This strategy is also the most effective intervention strategy, reducing the attack rate from 32% to 4.6%. The results indicate that strategies with the lowest total costs are also the most effective. For a category 5 pandemic the 6 most effective strategies, all of which reduce the attack rate to less than 10%, have total costs ranging from $1,584 to $2,748 per person, which is less than one-third the cost of the unmitigated pandemic ($8,550), showing the substantial net benefit of effective interventions for high severity pandemics. These strategies all feature continuous school closure, with either continuous community contact reduction or antiviral treatment and prophylaxis.

The ability of highly effective interventions to reduce the total cost of a high severity pandemic is due to the largest component of the overall cost being productivity losses arising from deaths. This is illustrated in Figure which shows the cost components for each intervention. It can be seen that the majority of the cost for an unmitigated pandemic of severity category 4 and 5 is due to death-related productivity losses (shown in purple). Although highly effective interventions incur large intervention-related productivity losses (shown in green), for high severity pandemics these intervention costs are more than outweighed by the reduction in medical costs and death-related productivity losses.

The most costly intervention considered (i.e. which still reduced the attack rate by at least 50%) is continuous school closure combined with continuous workforce reduction, which costs $4,804 per person.

Low severity pandemics

For low severity pandemics (in category 1, having CFR

<

= 0.1%) the intervention strategy with the lowest total cost considered is 8 weeks school closure combined with antiviral treatment and prophylaxis, costing $374 per person which represents a net saving of $67 per person compared to no intervention. However, this strategy is not as effective as other intervention strategies, reducing the attack rate to only 15%.

The most effective intervention (combined continuous school closure, community contact reduction, and antiviral treatment and household prophylaxis), which reduces the attack rate to 4.6%, costs $416 per person, a net benefit of $25 per person compared to no intervention. Figure shows that for category 1 and 2 pandemics, although highly effective intervention measures reduce medical costs and death-related productivity losses, they incur larger costs due to intervention-related lost productivity.

The most costly intervention considered is continuous school closure combined with continuous workforce reduction, which costs $1,217 per person, a net cost of $776 per person compared to no intervention. This is due to the large cost associated with 50% workforce absenteeism.

Non-pharmaceutical interventions

An important subset of intervention strategies are those consisting of purely social distancing interventions. In the case that antiviral drugs are unavailable or ineffective, only these non-pharmaceutical interventions strategies will be available. The most effective non-pharmaceutical strategy is the continuous application of the three social distancing interventions, school closure, workforce reductions, and community contact reduction, which reduces the attack rate to 6%. This intervention has a total cost ranging from $1,116 to $2,603 per person for severity categories ranging from 1 to 5 respectively.

The least costly non-pharmaceutical strategy omits workforce reduction, resulting in a slightly higher attack rate of 7%. This intervention has a total cost ranging from $447 to $2,275 per person for severity categories ranging from 1 to 5 respectively.

Results without death-related productivity losses

The costing model used for this analysis includes future productivity losses from deaths caused by the pandemic. This long-term cost is often not included in cost-utility analyses. The inclusion of death-related productivity losses greatly increases the total costs of severe pandemics. However, even if these costs are not included, medical costs (due to hospitalisation and ICU usage) play a similar, although less extreme, role. If long-term productivity losses due to death are not included in the costing model, the total cost of the pandemic is not surprisingly lower. However the effectiveness and

*relative total costs* of intervention strategies – that is, the ranking of intervention strategies by total cost - remains the same whether or not death-related productivity losses are included (Spearman’s rank correlation coefficient r

=

0.95, p

=

0.006 for a null hypothesis that rankings are uncorrelated). Full cost results of an alternate analysis that omits death-related productivity losses is contained in an additional file accompanying this paper (Additional file

1), and is summarised below.

For category 5, when death-related productivity losses are not included the total cost of intervention strategies ranges from $559 to $1,711. This range is much smaller than if death-related productivity losses are included, in which case total cost ranges from $1,799 to $4,804. For lower severity pandemics with lower case fatality ratios, the contribution of death-related productivity losses is naturally smaller. For category 1, when death-related productivity losses are not included total cost ranges from $314 to $1,089; with death-related productivity losses the range is $365 to $1,217.

If death-related productivity losses are not included, social distancing and illness costs dominate the total cost of each intervention strategy for low severity pandemics, while health care costs dominate the cost profile for high severity pandemics.

Sensitivity analyses

Sensitivity analyses were conducted to examine the extent to which these results depend upon uncertain model parameters that may impact on the cost or effectiveness of interventions. The methodology adopted was to identify assumptions and model parameters known to have an effect on intervention outcomes, taken from previous studies with this simulation model [

4,

5,

10,

11,

37,

52], and to perform univariate analyses on each, examining parameter values both significantly higher and lower than the baseline values. Alternative parameter settings were analysed for transmissibility (as characterised by the basic reproduction number R

_{0}), voluntary household isolation of symptomatic individuals, antiviral efficacy, compliance to home isolation during school closure, degree of workforce reduction, and degree of community contact reduction.

A common finding across all sensitivity analyses was that alternative parameter settings that rendered interventions less effective resulted in strategies that not only had higher attack rates, but also had higher total pandemic costs, with this effect being most pronounced for pandemics of high severity.

Further details and results of the sensitivity analysis can be found in an additional file accompanying this paper (Additional file

1).