The American Journal of Managed Care March 2010
Cost-Effectiveness of Pneumococcal Polysaccharide Vaccine Among Healthcare Workers During an Influenza Pandemic
Pneumococcal polysaccharide vaccination of healthcare workers during an influenza pandemic is cost-effective from a societal perspective but not from a hospital perspective without external subsidy.
Objective: To assess the usefulness and cost-effectiveness of pneumococcal polysaccharide vaccine (PPV) among healthcare workers compared with nonuse of PPV during an influenza pandemic.
Study Design: Markov modeling was used to estimate the cost-effectiveness of PPV in previously unvaccinated healthcare workers during an influenza pandemic.
Methods: Invasive pneumococcal disease (IPD) incidence rates were incorporated into the model, which assumed that IPD events occurred at twice the usual rate during a year of pandemic influenza. Societal and hospital perspectives were examined. Assumptions were that pneumococcal disease transmission from healthcare worker to patient did not occur, heightened IPD risk occurred for only 1 year, and PPV did not prevent noninvasive pneumonia, all of which potentially bias against vaccination.
Results: From a societal standpoint, PPV of healthcare workers during an influenza pandemic is economically reasonable, costing $2935 per quality-adjusted life-year gained; results were robust to variation in multiple sensitivity analyses. However, from the hospital perspective, vaccinating healthcare workers was expensive, costing $1676 per employee absence day avoided, given an IPD risk that (although increased) would remain less than 1%.
Conclusions: Vaccinating all healthcare workers to protect against pneumococcal disease during a pandemic influenza outbreak is likely to be economically reasonable from the societal standpoint. However, PPV is expensive from the hospital perspective, which might prevent implementation of a PPV program unless it is externally subsidized.
(Am J Manag Care. 2010;16(3):200-206)
A cause of extended morbidity and mortality in previous influenza pandemics has been invasive pneumococcal disease.
- In an influenza pandemic, healthcare resources will be strained as increased numbers of patients seek care and healthcare workers fall ill and cannot work.
- A potential means of preventing healthcare worker illness and absence from work is to vaccinate them with pneumococcal polysaccharide vaccine.
- From a societal perspective, this strategy is cost-effective, costing $3.14 per healthcare worker and $2935 per quality-adjusted life-year gained.
- From the hospital perspective, vaccinating healthcare workers was expensive, costing $1676 per employee absence day avoided.
Secondary pneumococcal infections caused as much as 20% of mortality during the 1918-1919 pandemic, as demonstrated in a review of autopsy series showing that 27% of blood cultures were positive for Streptococcus pneumoniae.2 This led to recommendations that pandemic preparedness plans comprise more than just influenza vaccination and include, for example, vaccination against pneumococcal disease.2,3
Vaccinating healthcare workers against pneumococcal disease is a strategy with significant potential, but it is not without countervailing arguments. For example, based on what is known about the efficacy of pneumococcal polysaccharide vaccine (PPV) against invasive pneumococcal disease (IPD), is this a cost-effective solution? Given the worldwide nature of a pandemic, potential costs associated with prevention measures must be considered. Furthermore, concerns about hyporesponsiveness (ie, immunologic interference from the first dose, limiting gains from a subsequent dose)4 raise the question whether vaccination of healthy healthcare workers during a pandemic merely shifts the burden of pneumococcal disease to later years, without changing the cumulative incidence of disease. The objective of this study was to use Markov modeling to assess the cost-effectiveness of PPV among healthcare workers compared with nonuse of PPV during an influenza pandemic. The results of these analyses will help health systems to anticipate needs and costs in their pandemic preparedness planning.
The cost-effectiveness of 23-valent PPV use among healthcare workers was compared with nonuse of PPV during an influenza pandemic using a Markov model, shown schematically in eAppendix A (available at www.ajmc.com). The model was programmed using available software (TreeAge Pro Suite; TreeAge Software Inc, Williamstown, MA). In the model, identical hypothetical cohorts of previously unvaccinated healthcare workers can remain well or develop IPD. Those developing IPD can recover completely, become disabled, or die of IPD. Risks of death from other causes for individuals in any health state can be determined from US life table data.5 Patients with disabilities due to IPD will die at higher rates. We model increases in IPD rates that might occur as a result of influenza but do not model influenza itself.
Three model assumptions were made that potentially bias it against PPV use in healthcare workers. The first assumption is that pneumococcal disease transmission from healthcare worker to patient does not occur. This assumption is based on pneumococcal disease resulting as an influenza complication in an individual already colonized with pneumococci and the unlikely possibility of simultaneous transmission of influenza and pneumococcus.6 The second assumption is that heightened IPD risk due to pandemic influenza occurs for only 1 year, as the duration of any influenza pandemic is unknown. The third assumption is that PPV does not prevent noninvasive pneumonia, as PPV protection against noninvasive pneumonia is unclear and controversial.6
Analyses were performed from societal and hospital perspectives. In the societal perspective analysis, the time horizon was 15 years with costs and benefits discounted at 3% per year, following the recommendations of the US Panel on Cost-Effectiveness in Health and Medicine.7 Effectiveness was valued in quality-adjusted life-years (QALYs) to account for changes in life span and quality of life due to PPV. Quality-adjusted life-years are the product of the time spent in a health state and the quality-of-life utility associated with that state summed over time; utilities are a measure of preference for a health state, ranging from 0 (death) to 1 (perfect health). In all analyses, costs were estimated in 2006 US dollars. In the hospital perspective analysis, the effectiveness term was employee absence day avoided over a 5-year time horizon, and the following 3 additional assumptions were made: (1) all direct medical costs are covered by insurance, (2) all healthcare workers with IPD miss work for 10 days, and (3) 2 months are required to replace healthcare workers who are disabled due to IPD or who die of IPD.
Age-specific IPD incidence data in eAppendix B (available at www.ajmc.com) were incorporated into the model.8 In the base-case analysis, we assumed that IPD cases and deaths occurred at twice the usual rate during the year of pandemic influenza in healthcare workers with a mean age of 45 years. This age was derived using US Bureau of Health Professions data for registered nurses and licensed practical nurses, who comprise the bulk of healthcare workers.9,10 We averaged the published age distributions of these workers to calculate the usual IPD rate for this cohort, 13.7 cases per 100,000, using CDC Active Bacterial Core surveillance data (eAppendix C available at www.ajmc.com).8 Using similar methods, we aged the cohort 15 years and calculated an IPD risk of 24.4 cases per 100,000 and then used linear interpolation to estimate IPD risk between years 1 and 15. We used the general population risk because there are no specific data on IPD risk in healthcare workers. Therefore, IPD rates were varied from 50% to 150% of their base-case levels in a separate sensitivity analysis.
The concept of increased pneumococcal disease rates is based on autopsy studies2,11 demonstrating pneumococcal bacteremia and empyema in the 1918-1919 pandemic and bacterial lung infection in the 2009 pandemic. Because the specific effect of influenza on IPD is unknown, we arbitrarily set IPD rates at twice the usual rate and varied the relative risk of IPD from 1 (no change in IPD rates) to 6 (6 times the usual IPD rates) in sensitivity analyses. The probability that IPD was caused by a pneumococcal serotype contained in the PPV was derived from CDC Active Bacterial Core surveillance data12 in eAppendix C. Costs related to vaccination and vaccination adverse events were also obtained from the literature,13-16 and age-specific IPD costs were obtained from the 2006 National Inpatient Sample (Table 1).17-21 A panel of pneumococcal disease experts estimated duration-specific protection from PPV for susceptible pneumococcal serotypes,12 basing their estimates on data by Shapiro et al22 (Table 2). Invasive pneumococcal disease–related meningitis incidence was used as a proxy for the probability of IPD-related disability.12
For all variables, the base-case value and range of values examined in 1-way sensitivity analyses are given in Table 1. Two-way sensitivity analyses were conducted to examine the combined effect of age and IPD rate variation on model results. To test the robustness of model results, parameter values were varied simultaneously in a probabilistic sensitivity analysis in which variables were assigned distributions and values were chosen from each distribution 5000 times. Uniform distributions were used for utility values, triangular distributions were used for hospital perspective costs, and clinical trial data and CDC data were assigned distributions based on data characteristics and skewness. Triangular distributions were also used to model estimates of PPV efficacy using the time-specific base-case estimates given in Table 2 as the most common value and the low-range and high-range efficacy estimates as the lower and upper bounds of these distributions.
Base-case results are summarized in Table 3. For healthcare workers with a mean age of 45 years and twice the usual IPD incidence and mortality rates during the pandemic influenza year, the per-patient total cost (including vaccination and IPD costs) for the PPV strategy was $3.14 greater than no vaccination, while gaining 0.00107 QALY (about 0.4 day). Therefore, the incremental cost-effectiveness ratio of vaccination compared with no vaccination was $2935 per QALY gained.
We estimated that 284 cases and 32 deaths per 100,000 healthcare workers would occur without PPV and that 171 cases and 19 deaths per 100,000 healthcare workers would occur with PPV. Therefore, a PPV strategy prevented about 40% of IPD cases and deaths in healthcare workers.
In 1-way sensitivity analyses in which parameter values were individually varied, results were most sensitive to healthcare worker age, with incremental cost-effectiveness ratios exceeding $100,000 per QALY for healthcare workers 29 years or younger (Figure 1). Conversely, pandemic-based PPV was cost saving for healthcare workers 49 years or older under base-case assumptions. Results were less sensitive to variation of IPD relative risk (eAppendix D available at www.ajmc.com). In a 2-way sensitivity analysis, we varied the healthcare worker age and the relative risk of IPD during an influenza pandemic year (Figure 2). Using an acceptability threshold of $100,000 per QALY gained, PPV would be favored for workers 29 years or older when the relative IPD risk is 1 or higher or for all workers (regardless of age) when the relative risk is 3.4 or higher.
When the base-case variables were used with a heightened IPD risk related to pandemic influenza lasting 2 years instead of 1 year, PPV costs $398 per QALY gained. If no increase in IPD rates occur with an influenza pandemic or if a pandemic occurs after PPV loses effectiveness (ie, after 15 years), PPV costs $6199 per QALY. While there is no standard criterion for cost-effectiveness, interventions that cost less than $100,000 per QALY gained are generally acceptable and are comparable to other commonly used interventions.23 Interventions that cost less than $20,000 per QALY gained are typically thought to be a “good buy” and to represent strong evidence for adoption.24 Evidence suggests higher acceptability thresholds for interventions related to occupational health,25 making our results even more favorable from that standpoint. The CDC Active Bacterial Core surveillance IPD risk data are risks for the general population; it is unclear if this risk applies to healthcare workers. Using 50% to 150% of the general public’s risk as a way to assess varying risk for healthcare workers, PPV in healthcare workers costs $31,600 per QALY if their IPD risk is 50% of the general population risk, and PPV is cost saving if healthcare worker risk is 150% of the general population risk.
In a probabilistic sensitivity analysis, all variable values listed in Table 1 were simultaneously varied. Vaccinating all healthcare workers was favored more than 91% of the time using an acceptability threshold of $20,000 per QALY and more than 99% of the time using an acceptability threshold of $100,000 per QALY.