2.1 Model Design

A de novo model was developed to capture both market and non-market productivity losses for patients with IMD and their caregivers in the USA, based on IMD cases diagnosed in 2021 [28]. Data from the year 2021 were modelled because of availability at the time the study was conducted. The model first estimated the number of cases of IMD attributed to serogroups A, B, C, W and Y in the USA (Sect. 2.3.1). For each IMD case, market and non-market time lost because of acute IMD, premature death due to IMD, reduced life expectancy from surviving IMD and/or IMD-related sequelae (Fig. 1, Table S1 of the Electronic Supplementary Material [ESM]) were estimated and multiplied by market and non-market time costs to obtain lifetime productivity losses.

Fig. 1

Model schematic. aThe model assumes that patients have a lifetime impact of most sequelae, and caregivers have a 10-year impact. bThe model assumes that patients and caregivers have varied proportions of earnings lost because of sequelae. IMD invasive meningococcal disease

The model followed the human capital approach (HCA), which factors in both market-related (working and work-related activities including travel) and non-market-related (unpaid household, caregiving, shopping, volunteering, secondary childcare and secondary eldercare) activities to determine overall productivity losses [29]. Use of the HCA is recommended by the Second Panel on Cost-Effectiveness in Health and Medicine to estimate the impact of health conditions on productivity in the USA [30]. To calculate the time individuals typically dedicate to market and non-market activities, data from the American Time Use Survey were used [29, 31, 32].

A 3% discount rate was applied to costs and outcomes [30], and a productivity growth rate of 1% was applied. Productivity costs were inflated to the 2023 US dollar (USD) [33].

2.2 Population

In the base case, lifetime market and non-market productivity losses were captured for IMD cases diagnosed in patients 16 years of age and older in 2021, alongside the losses of those patients’ caregivers. As IMD vaccination coverage is suboptimal among individuals 16–17 years of age according to National Immunization Survey-Teen data for 2022 [34], it is particularly important to capture the impact of IMD beginning at 16 years of age, especially considering the 2024–2025 review of the adolescent meningococcal vaccination schedule by the CDC and ACIP [35]. Additionally, given that the Fair Labor Standards Act limits the number of hours worked by minors under the age of 16 years in the USA [36], only adolescents 16 years of age and above were considered to be productive in terms of work (i.e. market productivity). In the base case, productivity losses of children under 16 years of age and their caregivers were excluded as a conservative assumption, given that child IMD survivors would not have market-based productivity losses, nor would their non-market losses be a large proportion of overall losses as children spend little time on household chores, caregiving, shopping, volunteering, secondary childcare and other secondary eldercare activities. However, as caregivers of patients with IMD under 16 years of age could still experience significant productivity losses, the impact of including caregivers of those children was explored in a scenario analysis. The lifetime productivity losses of patients with IMD themselves under 16 years of age were not included in either the base-case or scenario analysis, but it is acknowledged that including those individuals would likely substantially increase overall productivity losses associated with IMD.

2.3 Model Inputs and Assumptions2.3.1 Epidemiological Inputs

Epidemiological inputs were captured from the CDC data for IMD cases (Table S3 of the ESM) [28], as well as the case fatality rate (CFR) from 2006 to 2015 (Table S4 of the ESM) [37], as these data represented the most recent peer-reviewed published information on CFRs in the USA for IMD. The base case used IMD cases diagnosed in 2021 (the latest data available at the time of the analysis); additional analyses incorporated cases diagnosed during the period from 2015 to 2021.

2.3.1.1 Number of Acute IMD Cases

The number of acute cases of IMD was calculated by summing the number of MenB (n = 25) and MenACWY (n = 96) cases, resulting in a total of 121 acute cases [38].

2.3.1.2 Number of Premature Deaths Due to Acute IMD

The model defined ‘premature deaths due to acute IMD’ as those occurring within the first year of IMD onset. To determine the number of deaths from meningococcal disease cases occurring in 2021, the number of MenB and MenACWY cases were multiplied by age-group-specific IMD CFRs [37]. The total number of premature deaths from acute IMD was 19.

2.3.1.3 Number of Survivors of Acute IMD

The number of survivors of acute IMD was calculated by subtracting the number of deaths due to acute IMD (n = 19) from the total number of acute IMD cases occurring in 2021 (n = 121). The total number of acute IMD survivors was 102.

2.3.1.4 Number of Cases of IMD-Related Sequelae

The number of IMD-related sequelae cases was calculated by multiplying the number of survivors of acute IMD (n = 102) by the probability of sequelae occurring (0.6617), resulting in a total of 67 cases.

2.3.2 Productive Time Lost2.3.2.1 Time Lost Because of Acute IMD

The average productive time lost associated with acute IMD was estimated from age-specific hospital length-of-stay data for the three most frequent IMD manifestations (meningitis [50% of cases], meningococcal septicemia [30% of cases] and bacteremic pneumonia [15% of cases]) [5, 39]. To account for the remaining 5%, the distribution of IMD manifestations was adjusted in the present model so that meningitis, meningococcal septicaemia and bacteraemic pneumonia accounted for 52.6%, 31.6% and 15.8% of cases, respectively. The length-of-stay data were multiplied by the age-specific number of cases occurring in 2021 to obtain the total productive time lost. The model conservatively assumes that time losses for patients and caregivers are equivalent during the acute phase. The model also assumes that patients will return to 100% productivity after their hospital stay (if not experiencing sequelae).

2.3.2.2 Time Lost Because of Premature Death from Acute IMD

Long-term productive time lost because of premature death from acute IMD was estimated based on years of life lost. Years of life lost were estimated by subtracting the age at which meningococcal disease was acquired from the appropriate age-specific USA estimate of average life expectancy for the general population [40]. As described previously, the number of premature deaths due to acute IMD was calculated by multiplying the number of MenB and MenACWY cases by age group-specific IMD CFRs. Productivity losses because of premature death were only calculated for patients with IMD.

2.3.2.3 Time Lost Because of Reduced Life Expectancy of Acute IMD Survivors

Long-term productive time lost for acute IMD survivors was estimated based on years of life lost because of a reduced life expectancy. Acute IMD survivors have a shorter life expectancy than the general population, regardless of the occurrence of sequelae, as demonstrated in a French database analysis [7]. Years of life lost were calculated by subtracting the life expectancy of IMD survivors from the appropriate age-specific USA estimate of average life expectancy for the general population [40]. This difference in life expectancy was calculated for each age group, for which age group-specific productivity loss costs were applied. Productivity losses because of a reduced life expectancy were only calculated for patients with IMD.

2.3.2.4 Time Lost Because of Cases of IMD-Related Sequelae

Long-term sequelae-related productive time lost was estimated by multiplying the percentage reduction in productivity due to sequelae by the duration of sequelae impact. In the base case, the specific sequelae and sequelae occurrence rates from Shen et al. [6] (encompassing the time period from 2001 to 2020) were used (Table 1). Assumptions about the impact of sequelae on patients’ and caregivers’ productivity were derived from the literature [1, 24, 41, 42] and USA expert clinical opinion (obtained from three advisory board meetings held over July–September 2023 during which insights from five USA advisors with extensive experience in IMD, paediatric infectious diseases, pain medicine, physical medicine and rehabilitation and/or brain injury were directly captured) [43], considering both the percentage decrease in productivity because of sequelae and the duration of sequelae impact. For patients with IMD, the model assumes a lifetime impact on productivity for all sequelae except skin scarring, separation anxiety and attention-deficit hyperactivity disorder, and assumes only partial productivity losses that range from 0 to 54.6% except for blindness, which is assumed to result in 100% productivity loss (Table 2). For caregivers, the model assumes a 10-year impact of most sequelae, as it is assumed that caregivers eventually return to their original level of productivity. The majority of sequelae are assumed to have no impact on caregiver productivity, with blindness, severe neurological disorders, intellectual disability and separation anxiety expected to result in the greatest percentage decrease in productivity. Additional assumptions are presented in Table 2.

Table 1 Proportion of patients experiencing sequelae (2001–2020): base caseTable 2 Sequelae assumptions2.3.3 Productive Time Cost

Market and non-market productive time costs were calculated based on average wage rates, following the approach published by Grosse et al. [29] Market productive time costs were calculated using wage data published in 2023 (Table S2 of the ESM), [44] adjusted for total compensation using the 2016 benefit ratio in Grosse et al. [29] Non-market productive time costs were calculated using wage data and the benefit ratio from Grosse et al., therefore both values in this calculation were from 2016 [29]. The 2016 wage data used for non-market productive time costs were inflated to 2023 values for consistency across the market and non-market productive time costs used. The benefits ratios were not adjusted in the calculation of the productive time costs, in order to maintain consistency with existing models at the time that the original analysis was conducted; a scenario analysis (Scenario 3; see Sect. 2.4) utilises the 2023 benefits ratio for market and non-market productive time costs.

2.3.3.1 Market Productivity Wage Rate

To obtain the market productivity wage rate, age-specific weekly median earnings across all industries, based on US Bureau of Labor Statistics (BLS) data from quarter two of 2023 (Table S2 of the ESM) [44], were used to calculate mean hourly earnings (assuming a 40-h work week). The mean hourly wage rate was then increased with employer-paid benefits (e.g. retirement benefits, medical insurance) as a proportion of wage and salary incomes, reported as 23.4% by Grosse et al. [29] Therefore, to capture the market productivity wage rate, the mean hourly wage rate was multiplied by 1.234. In calculating the market productivity wage rate, acute IMD utilised total daily compensation while premature death from IMD, reduced life expectancy in IMD survivors and IMD-related sequelae utilised total annual compensation.

2.3.3.2 Non-Market Productivity Wage Rate

Similarly, to obtain the non-market productivity wage rate, the average mean hourly wage rate of personal care and service occupation workers ($14.01, multiplied by 40 to obtain weekly median earnings [Table S2 of the ESM]), estimated from 2016 wage data and inflated to 2023 quarter two USD, was adjusted for employer-paid benefits, reported as 17.9% by the BLS employer cost of employee compensation survey [29, 44]. Therefore, the adjusted non-market productivity wage rate was calculated by multiplying $14.01 by 1.179. In calculating the non-market productivity wage rate, all four epidemiological inputs utilised total annual compensation.

2.3.4 Calculation of Productivity Loss

The productivity loss cost was calculated for each epidemiological input by multiplying the productive time lost (Sect. 2.3.2) by the productive time cost (Sect. 2.3.3). Overall costs because of productivity losses in patients and caregivers were calculated by adding the found productivity loss cost of each epidemiological input.

Average productivity losses per IMD case were calculated for each epidemiological input and overall by dividing productivity losses by the total number of IMD cases diagnosed in 2021.

2.4 Scenario and Sensitivity Analyses

To account for variation in reported IMD-related sequelae, a scenario analysis (Scenario 1) calculated productivity losses employing sequelae rates from two additional studies (Table S5 of the ESM) [25, 45].

Another scenario analysis (Scenario 2) was conducted to quantify total market and non-market productivity losses when including the losses attributed to caregivers of patients with IMD under the age of 16 years. To ensure a conservative estimate, market and non-market losses for the patients themselves were not considered; as such, including lifetime productivity losses associated with children under the age of 16 years would likely increase the estimate substantially.

A third scenario analysis (Scenario 3) was conducted by multiplying the market productivity wage rate by 1.311 and the non-market productivity wage rate by 1.274 to reflect the updated data on employer-paid benefits from BLS as of December 2023 (Table S6 of the ESM) [46].

Additionally, a univariate sensitivity analysis was conducted to assess the impact of adjusting the epidemiological, sequelae and costs parameters on productivity losses (Table S7 of the ESM).