Cost-Effectiveness of Vaccination against Invasive Pneumococcal Disease among People 50 through 64 Years of Age: Role of Comorbid Conditions and Race

Context Pneumococcal vaccination is cost-saving for people 65 years of age and older, but the cost-effectiveness of extending routine vaccination to people 50 through 64 years of age is unknown. Contribution This cost-effectiveness analysis suggests that routine pneumococcal vaccination for people 50 through 64 years of age costs about $2500 for black people and $8200 for nonblack people at low risk to gain a quality-adjusted year of life, and saves costs for people at high risk for pneumococcal disease. Implications Policymakers and clinicians should take these findings into account when considering extending routine pneumococcal vaccine to individuals younger than 65 years of age. The Editors Policymakers are increasingly recommending age 50 years as a milestone for interventions to prevent disease (primary prevention) or to screen for asymptomatic disease for which treatment can prevent sickness and death (secondary prevention). Clinical guidelines have advised screening at age 50 years to detect early disease, such as breast and colorectal cancer, but only recently have begun to include vaccinations (1, 2). In 1999, the Advisory Committee on Immunization Practices, which advises the Centers for Disease Control and Prevention (CDC), recommended reducing the age for universal influenza vaccination from 65 years to 50 years. The Advisory Committee on Immunization Practices has also considered lowering the recommended age for universal pneumococcal polysaccharide vaccination from 65 years to 50 years. A cost-effectiveness analysis concluded that pneumococcal vaccination to prevent bacteremia in people 65 years of age or older conveys health benefits and saves medical costs (3). This result raised the question of the advisability of vaccinating adults younger than 65 years in age, especially black people, whose incidence of invasive pneumococcal disease is two to five times higher than that in white people (4, 5). After childhood, the risk for illness and death from the disease increases with age (5). Incidence per 100 000 population in 1998 increased from 3.9 for people 5 through 17 years of age to 7.4 for people 18 through 34 years of age, 16.0 for people 35 through 49 years of age, 23.0 for people 50 through 64 years of age, and 59.7 for people 65 years of age or older. The case-fatality rate also increases with age, from 1.4% for people younger than 2 years of age to 20.6% for those 80 years of age or older. Multiple administrations of this polysaccharide vaccine may not produce good immune responses each time. Although data on the clinical effectiveness of revaccination are lacking, serologic studies suggest that immune responses are lower after a second dose of pneumococcal polysaccharide vaccine than after the first dose (6, 7). The interest of the Advisory Committee on Immunization Practices in possibly lowering the recommended age for universal vaccination also stemmed from the low utilization rates in people with underlying conditions that put them at high risk for disease. Despite the recommendation that high-risk people younger than 65 years of age receive vaccination, cumulative vaccination rates have been low: Only about 20% of high-risk people 50 through 64 years of age and 12% of high-risk black people in this age group were vaccinated by 1995 (8). Perhaps vaccination would more effectively reach these high-risk people if the recommendation were based on age instead of underlying condition, since utilization rates for people 65 years of age or older, spurred by programs to promote universally recommended vaccination, increased to almost 55% by 1999 (9). Given the epidemiology of invasive pneumococcal disease, limitations of the current adult vaccine, and inadequate vaccination for high-risk people, policy issues center on the 50- through 64-year-old age group. Using cost-effectiveness analysis, we compared the likely health benefits and medical costs of vaccination and no vaccination for the total general immunocompetent, high-risk, and low-risk populations, 50 through 64 years of age, with separate analyses for black and nonblack people. The analysis excluded potential benefits for immunocompromised people. Methods Cost-Effectiveness Model In a Markov decision-tree model, we followed two hypothetical U.S. cohorts of vaccinated and unvaccinated people 50 through 64 years of age until death for the probability that they would incur invasive pneumococcal disease, die, or have average health (Figure). We used DATA, version 3.5 (TreeAge Software, Inc., Williamstown, Massachusetts), for analysis. The incremental medical costs of vaccination in 1995 U.S. dollars compared with the unvaccinated cohort was the sum of the vaccine costs, its administration, and treatment of adverse effects, minus savings in treatment costs from preventing invasive pneumococcal disease. The incremental health effect in quality-adjusted life-years (QALYs) was the total of increased years of life from preventing invasive pneumococcal disease, minus reductions from less-than-perfect health during surviving years. The analysis took a societal perspective, which included costs regardless of payer; calculated health and cost implications through life expectancies; and discounted future costs and health effects to reflect preferences for present over future events (10, 11). We applied the model to the total general immunocompetent, high-risk, and low-risk populations. Figure. Markov decision model. QALYs Sensitivity Analyses The base-case analysis, following current guidelines, includes only future medical costs related to invasive pneumococcal disease (10). Because related and unrelated costs may be difficult to distinguish, supplementary analyses added survivors' total future medical costs. In addition to the base-case analyses, which used the most probable values of each variable, one-way sensitivity analyses varied uncertain variables one at a time over reasonable ranges. In addition, global best-case and worst-case (multiway) analyses used the extreme values of these variables simultaneously. The best-case analysis used values of uncertain variables with the most favorable health and cost implications for vaccination, such as high incidence of invasive pneumococcal disease, case-fatality rates, vaccination effectiveness rates, and QALY weights, and the worst-case analysis used values least favorable for vaccination (Table 1). We also conducted probabilistic sensitivity analyses for black and nonblack people in the general immunocompetent population. Each variable in the model was represented by a triangular distribution, where the peak was equal to the base-case value and the lower and upper bounds were equal to the best- or worst-case values. We performed 1000 simulations to generate a distribution of cost-effectiveness ratios according to the cost-effectiveness plane (3). Table 1. Assumptions for the Base-Case Estimates and Sensitivity Analyses, 1995 Health Effects For invasive pneumococcal disease incidence, cases were defined by isolation of Streptococcus pneumoniae from a normally sterile body site. Most isolates are from blood (>90%) or cerebrospinal fluid (5% to 10%). Pneumonia is reported for at least 58% of patients with invasive pneumococcal disease 18 through 64 years of age (19). If vaccination protects against nonbacteremic pneumonia as well as invasive pneumococcal disease, our results underestimate benefits gained. General Immunocompetent Population For incidence of invasive pneumococcal disease and case-fatality rates, the base-case analysis used average rates of laboratory-confirmed disease from CDC active surveillance among defined populations in three citiesBaltimore, Maryland; San Antonio, Texas; and San Francisco, Californiaduring 1995 and 1996, by black or nonblack race and age group (Table 1). Data through 2000, which became available more recently, show no consistent pattern of change. From a casecontrol study with the best available age-specific data for immunocompetent patients, we derived vaccination effectiveness in preventing invasive pneumococcal disease caused by vaccine serotypes and duration of immunity (Appendix) (12). On the basis of these results, we estimated a maximum protection duration of 6 years, after which vaccinated and unvaccinated people had the same risk for death (Table 1). Following current guidelines, the analysis extends through life expectancies (10). We assumed that vaccination effectiveness and case-fatality are the same for all racial or ethnic groups. Although a casecontrol study of HIV-infected adults reported greater effectiveness in white people than in black people (20), we know of no data to indicate differences for immunocompetent people. The identical risk for death among black and white people in a recent multivariate analysis of bacteremic pneumococcal pneumonia supports the case-fatality assumption (19). The Appendix describes the all-cause mortality and quality-of-life calculations. High-Risk Immunocompetent Population The Advisory Committee on Immunization Practices recommends pneumococcal vaccination for immunocompetent people 2 through 64 years of age with chronic cardiovascular disease, including congestive heart failure and cardiomyopathies; chronic pulmonary disease, including chronic obstructive pulmonary disease and emphysema; diabetes mellitus; alcoholism; chronic liver disease, including cirrhosis; cerebrospinal fluid leaks; or asplenia. Shapiro and colleagues (12) also listed chronic renal failure requiring dialysis in their immunocompetent stratum, although the Advisory Committee on Immunization Practices considers patients with chronic renal failure to be immunocompromised. Combining this information with the comorbid conditions of people with confirmed invasive pneumococcal disease in the CDC database, we included people with congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, chronic renal failure, cirrhosis, or