infection control and hospital epidemiologymay 2008, vol. 29, no. 5
Economic Evaluation of Standing Order Programs
for Pneumococcal Vaccination of Hospitalized Elderly Patients
Donald B. Middleton, MD; Chyongchiou J. Lin, PhD; Kenneth J. Smith, MD, MS; Richard K. Zimmerman, MD, MPH;
Mary Patricia Nowalk, PhD, RD; Mark S. Roberts, MD, MPP; Dwight E. Fox, DMD
(See the commentary by Davis on pages 395-397)
mechanism to achieve high vaccination rates. Among the suggested settings for the utilization of SOPs are hospital inpatient units, because
they provide care for those most likely to benefit from vaccination. The cost-effectiveness of this approach for elderly hospitalized persons
is unknown. The purpose of this study was to estimate the cost-effectiveness of SOPs for pneumococcal polysaccharide vaccine (PPV)
vaccination for patients 65 years of age or older in 2 types of hospital.
Standing order programs (SOPs), which allow for vaccination without an individual physician order, are the most effective
implemented a nursing-based SOP for PPV. Newly admitted patients 65 years of age or older were screened for PPV eligibility and then
offered PPV. Vaccination rates before and after initiation of SOPs in the United States, incidence rates of invasive pneumococcal disease
in the United States, and US economic data were the bases of the cost-effectiveness analyses. One-way and multivariate sensitivity analyses
In 2004, a 1,094-bed tertiary care hospital implemented a pharmacy-based SOP for PPV, and a 225-bed community hospital
cost-effectiveness analysis, using a societal perspective, we found that both pharmacy-based and nursing-based SOPs cost less than $10,000
per quality-adjusted life-year gained, with program costs (pharmacy-based SOPs cost $4.16 per patient screened, and nursing-based SOPs
cost $4.60 per patient screened) and vaccine costs ($18.33 per dose) partially offset by potential savings from cases of invasive pneumococcal
disease avoided ($12,436 per case). Sensitivity analyses showed SOPs for PPV vaccination to be cost-effective, comparedwithPPVvaccination
without SOPs, unless the improvement in vaccination rate was less than 8%.
PPV vaccination rates increased 30.5% in the tertiary care hospital and 15.3% in the community hospital. In the base-case
PPV vaccination rates without SOPs.
SOPs do increase PPV vaccination rates in hospitalized elderly patients and are economically favorable, compared with
Infect Control Hosp Epidemiol 2008; 29:385-394
From the Departments of Family Medicine and Clinical Epidemiology (D.B.M., C.J.L., R.K.Z., M.P.N., D.E.F.), Radiation Oncology (C.J.L.), and Medicine
(K.J.S., M.S.R.), University of Pittsburgh School of Medicine, and the Departments of Behavioral and Community Health Sciences (C.J.L., R.K.Z.) and
Health Policy and Management (C.J.L., M.S.R.), University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
Received September 17, 2007; accepted January 29, 2008; electronically published April 3, 2008.
? 2008 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2008/2905-0001$15.00.DOI: 10.1086/587155
Infection due to Streptococcus pneumoniae can lead toinvasive
pneumococcal disease (IPD), including infection of the me-
ninges, joints, bones, body cavities, or bloodstream (bacter-
emia). The case-fatality rate for pneumococcal bacteremia is
15%-20% among younger adult patients and 30%-40%
among elderly patients.1The Advisory Committee on Im-
munization Practices of the Centers for Disease Control and
Prevention has recommended a 23-valent pneumococcal
polysaccharide vaccine (PPV) for all persons 65 years of age
and older, to reduce the risk of IPD. Despite estimates of
56%-81% effectiveness of PPV for preventing IPD,2,3the PPV
vaccination rate among persons 65 years of age or older has
plateaued: it was 56.2% in 2002, 57% in 2004, and 56.2% in
2005.4,5Rates remain well below the Healthy People 2010 goal
of 90% for the noninstitutionalized elderly population.6Ad-
ditionally, racial disparity in the PPV vaccination rate for the
elderly population persists: it is 60.7% for non-Hispanicwhite
persons, 38.9% for non-Hispanic black persons, and 27.6%
for Hispanic persons.5Although the duration of vaccine pro-
tection is unknown, within 6-10 years, antibody levels against
many strains in the vaccine are markedly reduced,particularly
in elderly persons who may develop lower initial antibody
levels in response to PPV. Thus, some studies question the
long-term effectiveness of PPV in the elderly population.7
Because of both advanced age and underlying illness, hos-
pitalized or institutionalized elderly persons are atparticularly
high risk for S. pneumoniae infections.1IPD is likely to ex-
acerbate underlying dysfunction of already challenged organ
systems. Fisman et al.8have demonstrated that prior PPV
vaccination improves survival, reduces respiratory failure
386infection control and hospital epidemiology may 2008, vol. 29, no. 5
participating hospitals. The recommendation of the Advisory Committee on Immunization Practices for PPV for most peopleis 1vaccination
after 65 years of age. RN, registered nurse.
Component tasks of the standing order programs for vaccination with pneumococcal polysaccharide vaccine (PPV) at
rate, and decreases length of stay for persons who are hos-
pitalized because of community-acquired pneumonia. Pre-
vious research has found that 36%-70% of patients who de-
veloped IPD had been hospitalized for other reasons within
the past 5 years, and has suggested vaccinating hospitalized
patients to maximize the effectiveness of immunization
programs.9,10However, only 45% of persons 65 years of age
or older who were hospitalized at least once for any reason
during the preceding year reported receiving PPV vaccina-
tion.11Several studies suggest that standing order programs
(SOPs) for PPV vaccination are the most efficient means of
improving vaccination rates in hospitals.12-15
Although PPV vaccination is cost-effective for the elderly
population in general,16the cost-effectiveness of a PPV vac-
cination program utilizing SOPs for hospitalized elderly pa-
tients has not been fully examined. This study was designed
to estimate the cost-effectiveness of a SOP for PPV vacci-
nation for inpatients 65 years of age and older in both a
tertiary and a community hospital, compared with PPV vac-
cination rates without SOPs. The study involved direct ob-
servation of the PPV vaccination screening process, vaccine
administration time, and the program costs associated with
those activities, which offers a unique perspective.
Setting and Procedures
The University of Pittsburgh Medical Center Health System
is a comprehensive network of tertiary, specialty, and com-
munity hospitals in western Pennsylvania. Beginning in 2001,
staff at several hospitals of this network initiated routine or-
ders for PPV vaccination of elderly inpatients. After the
changes in the Medicare regulations allowing vaccination in
hospitals without a signed physician order,17these programs
were converted into SOPs.18,19
The medical executive committee of the network approved
SOPs specific to each facility, and thus patients 65 years of
age and older were administered PPV without a specific order
from the attending physician. SOPs were implemented by the
pharmacy staff at a 1,094-bed tertiary care facility and by the
nursing staff at a 225-bed community hospital. At the tertiary
care hospital, a pharmacy technician scanned the list of newly
admittedpatients on a dailybasistocheckforeligiblepatients.
At the community hospital, a registered nurse from the ad-
mitting team interviewed all newly admitted patients and
reviewed the electronic medical record for eligible patients.
Attending physicians were informed about theSOPs.Hospital
personnel administering vaccine were required to participate
in educational and training sessions, to learn the components
of the SOPs and the procedures for administering PPV based
on the approved vaccine delivery protocols. The components
of the SOPs are listed in Figure 1. For cost-effectiveness anal-
ysis, the combined cost of vaccine and of complying with the
SOPs was weighed against the estimated cost savings from
reduced IPD, to determine the net costs.
Data Sources and Assumptions
Centers for Disease Control and Prevention’s Active Bacterial
Core surveillance (ABCs) in the United States during 2003-
2004, we used the average incidence rate of IPD per 100,000
population as the base-case value (Table 1). Vaccinated per-
sons have a lower IPD incidence rate than do unvaccinated
persons. Therefore, currently reported IPD incidence rates
underestimate the rate in an unvaccinated population, be-
cause some of the population has been vaccinated. Unfor-
tunately, measured IPD incidence rates for unvaccinated per-
sons, compared with vaccinated persons, are unavailable.
Thus, IPD incidence rates were estimated separately among
unvaccinated and vaccinated persons using the 2003-2004
ABCs data (unpublished) on IPD incidence rates, data from
On the basis of the data collected by the
economic evaluation of sops for inpatient ppv vaccination 387
the 2004 National Health Interview Survey on the proportion
of persons vaccinated with PPV,20and data from Robinson
et al.26on the proportion of IPDs caused by vaccine serotypes.
To calculate the likelihood of a person developing IPD after
vaccination, we assumed that the vaccinated person would
develop IPD from nonvaccine pneumococcal serotypes at the
mean incidence rate for that person’s particular age group
but would be proportionally protected—weighted by the age
distribution of the patient population—from vaccine-related
serotypes on the basis of the effectiveness of the vaccine over
Vaccination rates. Data on inpatient vaccination rates
were gathered from a review of electronic and paper medical
records. Data on the total number of inpatients 65 years of
age and older—those who refused PPV vaccination, those
with prior PPV vaccination, or those newly vaccinated with
PPV—were obtained for each hospital. The PPV vaccination
rate was calculated as follows: (number of inpatients x65
years of age receiving PPVvaccinationathospital)?(number
of inpatients x65 years of age ? number of patients with
prior PPV vaccination). In the tertiary care hospital, thephar-
macy kept daily records of all PPVs. Data were collected from
the periods before implementation (from July 2002 through
June 2003) and after implementation (from May 2004
through April 2005) of the SOP. Data from July 2003 through
April 2004 were not used because this was the period during
which the SOP was being introduced in the hospital, and
therefore the PPV vaccination rate would be expected to be
changing. In the community hospital, data on the PPV vac-
cination rate were obtained by review of medical charts of
patients admitted before implementation (October 2003) and
after implementation (October 2004) of the SOP. Data from
the same month for each year were used to avoid seasonal
variability, and October was selected because it coincides with
influenza season, when there is a heightened awareness of the
need for both influenza and PPV vaccinations. Because of
the considerable time required for manual review of medical
records, data were reviewed for patients admitted during a
single month for each year.
Cost of vaccine and of vaccine administration.
cost of PPV incurred by the hospitals varied; the lowest price
was used as the best case, the highest price was used as the
worst case, and the mean price was used as the base case.
The actual acquisition cost of PPV incurred by the hospitals
studied was used because it is a realistic proxy of the societal
cost of a hospital-based vaccination policy. The average
wholesale cost of a dose of PPV in 2003, $19.30, was included
in the range of values examined in sensitivity analyses.
To assess the cost of administration of PPV, research as-
sistants used stopwatches to measure the time required to
accomplish each segment of the process, which included
screening for eligible individuals on admission,reviewingvac-
cination status with the patient or with the patient’s repre-
sentative, assessing the patient’s willingness to receivevaccine,
communicating the order to the pharmacy, processing the
order, reviewing files to prevent inappropriate revaccination,
filling the order, presenting and explaining the Vaccine In-
formation Statement, administering the vaccine, and record-
ing vaccine administration. The salary for each staff position
involved was based on the midpoint hourly wage plus 25%
for benefits. Actual hospital PPV administration costs were
used as a proxy for the societal cost of a hospital vaccination
Additional planning, education, and trainingactivitieswere
associated with the SOPs. Because these onetime costs are
fixed, the average fixed costs per vaccination declined as more
patients were vaccinated and thus were assumed to approach
zero in the long term, although newly hired staff would still
Costs of treatment. Treatment costs attributable to IPD
were conservatively limited to the expenses associated with
hospitalization. Robinson et al.26reported that almost all pa-
tients with IPD who were 50 years of age or older were likely
to be hospitalized. Although the societal perspective typically
includes all direct and indirect costs of illness, few data are
available on the direct nonhospital medical costs of IPD (eg,
outpatient care and rehabilitation) or the indirect costs of
seeking or receiving care, such as transportation and caregiver
and/or patient time.27As a result, we used hospitalization
costs attributable to IPD as a proxy for societal cost, with the
understanding that this assumption biases the analysis against
The Nationwide Inpatient Sample (NIS) data of 2003 were
used to estimate the hospitalization cost attributable to IPD
per admitted patient.23Because the NIS data do not provide
the true cost of hospitalizations, charges for hospitalization
were adjusted by means of the hospital’s cost-to-charge ratios
from the Medicare cost report.28In addition, because of dif-
ferences in wages in different areas, the hospital charges were
also adjusted by means of the wage index.28The discharge
sample weights from the NIS database were used to create
national estimates of hospitalization cost per patientadmitted
(QALYs) are a measure of the effectiveness of an intervention.
The quality-of-life weights for healthy persons by age used
in these analyses were taken directly from published sources.29
We assumed that elderly patients with IPD had limited in-
strumental activities of daily living, so their QALYs were less
in the hospital than out.29The average length of hospital stay
for patients with IPD was estimated using the 2003 NIS da-
tabase and was used to calculate QALY losses during their
period of hospitalization. The average length of hospital stay
for patients with bacteremia was the shortest among all se-
lected codes from the International Classification of Diseases,
9th Revision, whereas the average length of hospital stay for
patients with meningitis was the longest. These 2 average
lengths of hospital stay were used as the best-case and worst-
case assumptions, respectively. Data from Shapiro et al.10were
used to derive a declining polynomial curve for the protective
388 infection control and hospital epidemiologymay 2008, vol. 29, no. 5
Analyses for Standing Order Programs for Vaccination with Pneumococcal Polysaccharide Vaccine (PPV)
Variables Used in the Decision Analysis Model and Ranges of Values Examined in the Sensitivity
Range of values
used in analysis
source of data
Patient age, years
Incidence rate, IPD cases per 100,000
population, by patient age
Proportion of IPD cases caused by vaccine
serotypes, %, by patient age
PPV vaccination rate, %, by patient age
Inpatient case-fatality rate for IPD, %,
by patient age
Vaccine efficacy, %, year after vaccination
NHIS  (baseline)
Husain et al.  (range)
CDC 2006  (range)
NIS (HCUP) 2003 
Lexau et al. 14.3
Weaver et al.  (years 1-6)
invasive pneumococcal disease; NIS HCUP, Nationwide Inpatient Sample Healthcare Cost and Utilization Project.
ABCs, Active Bacteria Core surveillance unpublished data; CDC, Centers for Disease Control and Prevention; IPD,
efficacy of PPV (Appendix), with the assumption that the
level of protection from PPV against IPD rapidly declines
over time so that, after 9 years, there is no protection.
Cost-effectiveness analysis. A decision tree model was con-
structed to separately compare 2 strategies (PPV vaccination
with and without SOP) in 2 types of hospital (Figure 2). In
the model, the decision (at the square node) is whether or
not to implement an SOP for inpatientPPVvaccination.With
or without the program, patients have a probability of being
vaccinated at the circular chance node, after which they may
transition, on a yearly basis, between the states of average
health, incident IPD, or death (which is designated in the
figure by a state-transition diagram [also known as the Mar-
kov model]). On the basis of US mortality tables, patients of
average health may die of non-IPD causes or, on the basis
of ABCs population data, may become ill with IPD. Similarly,
patients with IPD may die of non-IPD causes or of IPD itself
during the yearly cycle in which IPD occurs. Non-IPD costs
and cost-effectiveness values in persons of average health are
assumed to be the same regardless of the presence of an SOP.
The model cycles until everyone in the cohort has died, thus
leaving a lifetime time horizon.
The economic analysis of the SOP for PPV vaccination
from the societal perspective was performed to estimate cost-
effectiveness ratios for each participating hospital. The nu-
merator of the cost-effectiveness ratio was calculated as the
change in the net costs (savings) before and after the imple-
mentation of the SOP by adding the administrative cost of
the SOP and the vaccine cost, and then subtracting the costs
per IPD case averted. The denominator for the cost-effec-
tiveness ratio was the change in QALYs before and after im-
plementing the SOP. All costs are in 2003 US dollars. Ac-
economic evaluation of sops for inpatient ppv vaccination389
for vaccination with pneumococcal polysaccharide vaccine.
Decision analysis model for prevention of invasive pneumococcal disease (IPD) with and without a standing order program
Utilities and Costs Used in the Decision Analysis Model and Ranges of Values Examined in the
Range of values
used in analysis
source of data
Average health utility weight, by patient age
IPD utility weight
Vaccination rate, %
Before SOP at tertiary care hospital
After SOP at tertiary care hospital
Before SOP at community hospital
After SOP at community hospital
Vaccine cost per dose
Administration cost per patient
Adverse event cost per dose received
Hospitalization cost per admitted patient
Length of stay, days
Discount rate, %
Erickson et al. 
0.1-0.5Sisk et al. 
18.3316.33-23.60 Hospitals studied
Sisk et al. 
NIS HCUP 
NIS HCUP 2003 
Gold et al. ; Sisk et al. 
aMean cost of bacteremia.
bMean cost of meningitis.
IPD, invasive pneumococcal disease; NIS HCUP, Nationwide Inpatient Sample Healthcare Cost and Utilization Project.
cording to current guidelines for cost-effectiveness analysis,
costs and effectiveness were discounted at 3%.27
Sensitivity analysis. In addition to the primary cost-ef-
fectiveness analyses, one-way and multivariate sensitivity
analyses27,30were conducted to examine the robustness of the
cost-effectiveness ratio estimates. Tables 1 and 2 list the pa-
rameters used in the decision analysis model and the ranges
of values examined in the sensitivity analyses. These param-
eters were varied simultaneously in probabilistic sensitivity
analyses, in which a value was randomly drawn from each
parameter distribution and the cost-effectiveness of each
strategy was calculated. This procedure was repeated 5,000
times. Parameter distributions were chosen on the basis of
parameter type and level of certainty for its distribution. Pa-
rameters with least-certain distributions (utilityweights)were
assigned uniform distributions, in which all values in a range
are equally likely to be chosen; all other parameters, in which
the range and peak values were known, were assigned tri-
angular distributions, except for vaccination rates,whichwere
assigned b distributions. Treatment costs were estimated us-
ing SAS, version 9.1 (SAS Institute).
TreeAge Pro 2006 software (TreeAge Software) was used
for the cost-effectiveness and sensitivity analyses. The x2tests
using SPSS software, version 12.0.1 (SPSS), were performed
to compare vaccination rates before and after the implemen-
tation of SOPs. Statistical significance was set at
all tests. The institutional review board of the University of
Pittsburgh approved this project.
forP ! .05
390infection control and hospital epidemiology may 2008, vol. 29, no. 5
saccharide Vaccine Vaccination
Cost-Effectiveness of a Standing Order Program (SOP) for Pneumococcal Poly-
Cost per patient
Tertiary care hospital
implementation. Solid lines, thresholds for the tertiary care hospital; dashed lines, thresholds for the community hospital; cross, observed
values for the community hospital; square, observed values for the tertiary hospital. PPV, pneumococcal polysaccharide vaccine; QALY,
Two-way sensitivity analysis that simultaneously varies vaccination rates before and after standing order program (SOP)
In the tertiary care hospital, 122 (4.6%) of 2,631 PPV-eligible
elderly patients were vaccinated before the implementation
of the SOP, whereas 1,271 (35.1%) of 3,626 PPV-eligible el-
derly patients were vaccinated after the implementation
( ). In the community hospital, none of the 315 eli-P ! .001
gible elderly patients received PPV before the implementation
of the SOP, whereas 33 (15.3%) of 215 were vaccinated after
the implementation ( ). Using data collected from theP ! .001
tertiary hospital, our model predicted that 8.0% of IPD hos-
pitalizations and 5.8% of IPD deaths would be preventedover
the patients’ lifetimes by onetime vaccination resulting from
an SOP, whereas 3.2% of vaccinees would have an adverse
reaction.32However, the incidence of significant reactions was
lower than expected. Three patients (0.2%) out of the first
1,500 vaccinees reported serious adverse events after vacci-
nation. One patient had high fever and remained hospitalized
for an additional day, but this patient also had cardiovascular
disease, and the exact reasons for the extra day spent in the
hospital were unclear. Two other patients only had injection
site soreness and did not incur additional costs. Elective sur-
gery for 1 of these patients was canceled. Records of minor
local reactions to vaccination were not kept in this study.
The program costs were $4.16 per patient screened for the
pharmacy-based SOP and $4.60 per patient screened for the
nursing-based SOP; vaccine cost was $18.33 per dose. Given
that adverse events after vaccination were rare and difficult
to assign to PPV, we included the average adverse event cost
per vaccine dose received as $0.03.4
In the base-case cost-effectiveness analysis, from a societal
perspective, both the pharmacy-based and nursing-based
SOPs cost less than $10,000 per QALY gained (Table 3). In-
economic evaluation of sops for inpatient ppv vaccination 391
Curves represent the likelihood that SOPs would be considered cost-effective for the willingness-to-pay (or acceptability) thresholds
represented on the x-axis.
Cost-effectiveness acceptability curves for standing order programs (SOPs) in the tertiary care and community hospitals.
cremental costs per patient screened were less than $4 for
either program. Savings from IPD cases avoided (at a cost of
$12,436 per case) partially offset these costs.
In sensitivity analyses, an SOP for PPV vaccination cost less
than $20,000 per QALY gained, unless the absolute improve-
ment in vaccination rate was less than 8% in the hospital.
SOPs remained less than $20,000 per QALY with individual
variation of other model parameters, including age, vaccine
effectiveness, and IPD severity, over plausible ranges. Costs
would be saved if SOPs resulted in an absolute increase in
vaccination rates of 56% or more, compared with vaccination
rates before the SOPs, if costs were $4.16, as at the tertiary
care hospital, or if the absolute vaccination rate increased
62% or more and costs were $4.60, as at the community
hospital. The effects of simultaneouslyvaryingthevaccination
rates before and after the SOPs are shown in Figure 3.
Further effects of simultaneously varying vaccination rates
and SOP costs were explored. If program costs are $5 or less
and absolute vaccination rates improve by 9% or more, SOPs
cost less than $20,000 per QALY; if costs are $10 or less and
absolute vaccination rates increase by greater than 17%, SOPs
cost less than $20,000 per QALY. Conversely, SOPs cost less
than $20,000 per QALY if programs improve absolute vac-
cination rates by at least 10% and program costs are not
greater than $6 per patient screened, or if absolutevaccination
rates increase at least 20% and program costs are not greater
A probabilistic Monte Carlo sensitivity analysis was per-
formed. Results are shown in Figure 4 in the form of cost-
effectiveness acceptability curves, showingthe probabilitythat
SOPs would be considered cost-effective in each setting for
a variety of societal willingness-to-pay thresholds. For the
tertiary care hospital, the SOP was cost saving in 20.9% of
model iterations, and would be preferred in 86.0% if the cost-
effectiveness acceptability threshold is $20,000 per QALY
gained. For the community hospital, the SOP was cost saving
in 8.7% of the Monte Carlo iterations, and would be preferred
54.7% or 77.3% of the time if acceptability thresholds are
$20,000 or $100,000 per QALY, respectively.
Although SOPs might better serve the whole population if
utilized in targeted outpatient settings to reach a larger num-
ber of potential vaccinees, they are the most effective method
to improve vaccination rates in the hospital. This study is the
first to directly assess the costs of SOPs for PPV in both a
community hospital and a tertiary hospital. Using cost-ef-
fectiveness analyses, SOPs for PPV were shown to be cost-
effective in both the base-case analysis and most sensitivity
analyses in these 2 settings. Although our measured cost find-
ings for PPV administration are somewhat lower than the
estimated costs in a recent study conducted by Honeycutt et
al.15in North Carolina, the range of costs for PPV from these
2 studies are still reasonable enough to justify its continued
use, especially when SOPs are utilized. The difference in the
SOP-stimulated vaccine rates between the tertiary care hos-
pital (35.1%) and the community hospital (15.3%) may be
related to the type of SOP used (pharmacy and nursing, re-
spectively) or to the large referral base in the tertiary care
hospital, compared with the patients with prior PPV admin-
istration admitted to the community hospital.
With medical interventions, such as the SOP, the evidence
for adoption is generally considered strong if the incremental
392 infection control and hospital epidemiologymay 2008, vol. 29, no. 5
cost-effectiveness ratio is $20,000 or less per QALY gained,
moderate if the ratio is between $20,000 and $100,000 per
QALY gained, and weak if the ratio is greater than $100,000
per QALY gained.33Both of the SOPs utilized in this study
led to costs well below the $20,000 per QALY benchmark.
PPV vaccination compares favorably with other recom-
mended vaccination programs: influenza vaccination of the
elderly population has been estimated to be cost saving,34,35
whereas vaccination to prevent herpes zoster in the elderly
population costs between $44,000 and $201,000 per QALY
depending on the age of the patient and the cost of
Despite studies establishing the efficiency of SOPs for im-
proving the PPV vaccination rate,12-14,38increasing the rate of
vaccination is still a challenge for most hospitals, because of
a focus on acute care and/or surgery, staffing limitations, and
concern about reimbursement; early discharge for many pa-
tients, which limits the opportunities for vaccination; and
resistance to inpatient vaccination among physicians and
staff.39To remove the physician-resistance barrier to PPV vac-
cination of hospitalized elderly patients, the federal govern-
ment, through the Centers for Medicare and Medicaid Ser-
vices, revised its regulations on standing orders to allow PPV
vaccination without a specific physician’s order.17In a survey
of 5 different types of institutions serving at-risk elderly pop-
ulations, Goldstein et al.40reported that one of the primary
barriers to adopting SOPs for PPV vaccination was that ad-
ministrators were not convinced of the benefits of imple-
menting such policies, but successful SOPs have been im-
plemented in both tertiary teaching and community
hospitals.19,41Because of the Hospital Quality Alliance and
Medicare Quality Improvement Organization initiative, all
acute care hospitals are currently required to report the num-
ber of pneumococcal vaccination screenings and/or collect
data on the rate of vaccination, and this has prompted hos-
pitals to develop inpatient vaccination programs. However,
as of March 2006, only 4 states had laws that required offering
PPV to hospitalized patients.42The economic benefits of com-
pliance with state and federal regulations and of developing
payment systems for keeping some classes of patients, such
as those with congestive heart failure, out of the hospital help
to mitigate administrative resistance. As the population ages,
more and more people will be at risk for IPD, further
strengthening the argument that all hospitals and long-term
care facilities need to have effective SOPs in place.
Limitations and Strengths
The costs of educating attending physicians about vaccinating
their PPV-eligible patients without their specific order and of
reeducating nursing or pharmacy staff who, under federal
regulations and a facility’s SOP, are permitted to administer
PPV without a physician-signed order were not included in
the analyses. Although these costs can be substantial, de-
pending on the receptivity of the organization to adopting
SOPs, they are fixed and will likely not continue once the
SOP has been established. Several model programs are now
available to reduce these initial costs.19,41Although we in-
cluded personnel costs, an argument can be made to exclude
personnel costs on the basis that administrators are unlikely
to hire staff solely for SOP support but rather could prioritize
this program over less important tasks.
The adjusted population-based IPD incidence rate used in
this study could possibly underestimate the incidence rate for
a cohort of hospitalized elderly patients who are presumably
at a higher risk of infection than the general population.
However, the IPD incidence rate is not available for such a
cohort. Performing identical analyses with a higher IPD in-
cidence rate would result in a more economically favorable
evaluation of SOPs for PPV vaccination than was found in
this study. Moreover, because we used the most recent ABCs
data, our findings account for the reduced incidence of IPD
among the elderly due to the widespread use of the 7-valent
pneumococcal conjugate vaccine among children. Some evi-
dence suggests the spread of serotypes not included in this
vaccine in the elderly, further justifying the administration
of PPV that includes these serotypes.43The effects of a po-
tential enhanced childhood pneumococcal conjugate vaccine
with 10-13 serotypes on IPD in the elderly are unknown.
Because studies of the efficacy of PPV against pneumonia
without bacteremia in the United States have been incon-
clusive,16,44-53these analyses were based on a conservative as-
sumption that PPV vaccination had no effect on the non-
invasive pneumococcal disease rate. Nonetheless, SOPs for
PPV vaccination in 2 different types of hospital were shown
to be cost-effective. Furthermore, analyses were limited to
hospital-related expenses. Substantial controversy has sur-
rounded the question of whether or not cost-effectiveness
analysis should include the future medical costs of survivors.27
However, the costs before and after hospital care, the loss of
individual productivity, long-term sequelae from IPD, and
the mental suffering associated with IPD are likely to be sig-
nificant. The fact that these analyses probably underestimated
total disease costs should enhance the cost-effectiveness of
SOPs for PPV.
The results of cost-effectiveness analysis were based on the
change in vaccination rates. In addition, a variety of base-
case vaccination rates were included in the Monte Carlo anal-
ysis. Therefore, these results should be sustained regardless
of base-case vaccination rate among inpatients. The intro-
duction of the hospital-based SOPs for PPV spurred many
physicians who admitted patients to the study hospitals to
establish similar SOPs in their own offices. As a result, the
current overall vaccination rate (adding prior vaccination to
current vaccination) at the community hospital is intherange
recommended by Healthy People 2010,6varying from 88%
to 97% with each monthly check. Establishing SOPs for PPV
helped produce cultural changes in both hospitals in which
the importance and practicality of implementing routine pre-
ventive health measures for hospitalized patients was rec-
economic evaluation of sops for inpatient ppv vaccination 393
ognized. Finally, multiple sensitivity analyses, including prob-
abilistic sensitivity analyses to change multiple variables, were
conducted. The SOPs for PPV remained cost-effective despite
The possibility for unwarranted extra doses of PPV exists
if hospital records are not universally available to other in-
stitutions. Walker et al.54reported few serious effects among
patients who received 3 or more doses of PPV; 1 of 170
persons had a serious reaction, and only 5 saw a doctor for
The ability to generalize these findings may be limited be-
cause this study was conducted in a single region of the
country. However, this limitation is attenuated by the inclu-
sion of both a community hospital and a tertiary care hospital
in the analysis.
SOPs for PPV were determined to be inexpensive to admin-
ister and economically favorable, compared with no program,
and to result in improved PPV vaccination rates among hos-
pitalized elderly patients in both a community hospital and
a tertiary care hospital. An SOP is cost-effective in both base-
case and sensitivity analyses.
We thank Susan J. Skledar, RPh, and Denise R.Sokos,PharmD,forfacilitating
the pharmacist-based SOP, Kelly A. Ervin and Sing-Ling Tsai for collecting
the PPV vaccination data, and Abigail Shefer, MD, FACP, and Mark Mes-
sonnier, PhD, MS (Centers for Disease Control and Prevention) for advice
regarding the execution of the study.
Financial support. This publication and project were made possible
through a cooperative agreement between the Centers for Disease Control
and Prevention and the Association for Prevention Teaching and Research
(award number TS-1057).
Potential conflicts of interest. D.B.M. reports an association with Merck
& Co., as a member of their speakers bureau.
The likelihood of IPD after vaccination was calculated as
I p I # [(1 ? P ) ? P # (1 ? V )],
VR VT VTE
where IVis the IPD incidence among vaccinated patients, IR
is the reported IPD incidence, PVTis the reported proportion
of IPD cases due to vaccine-related serotypes, and VEis the
vaccine efficacy in percent. Unvaccinated persons willdevelop
IPD as a function of national IPD and vaccination rates, and
of IPD rates in vaccinated persons. The likelihood of IPD in
unvaccinated persons was calculated as follows:
I p [I ? (I # P )] ? (1 ? P ),
where INis IPD incidence among unvaccinated patients and
PVis the proportion of the population that is vaccinated.
The equation of a polynomial curve for vaccine efficacy of
PPV was derived as follows:
Y p 85 ? 1.75Z ? 0.875Z ,
where Z is the number of years since vaccination and Y is
the vaccine efficacy in percent.
Address reprint requests to Chyongchiou J. Lin, PhD, Department of Ra-
diation Oncology, University of Pittsburgh School of Medicine, 535 UPMC
Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA 15232 (firstname.lastname@example.org).
The contents of this article are the responsibility of the authors and do
not necessarily reflect the official views of the Centers for Disease Control
and Prevention or the Association for Prevention Teaching and Research.
1. Centers for Disease Control andPrevention.Preventionofpneumococcal
disease: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep 1997; 46:1-24.
2. Rubins JB, Janoff EN. Pneumococcal disease in the elderly: what is pre-
venting vaccine efficacy? Drugs Aging 2001; 18:305-311.
3. Butler JC, Breiman RF, Campbell JF, Lipman HB, Broome CV, Facklam
RR. Pneumococcal polysaccharide vaccine efficacy: an evaluation of cur-
rent recommendations. JAMA 1993; 270:1826-1831.
4. Sisk JE, Whang W, Butler JC, Sneller VP, Whitney CG. Cost-effectiveness
of vaccination against invasive pneumococcal disease among people 50
through 64 years of age: role of comorbid conditions and race. Ann
Intern Med 2003; 138:960-968.
5. Centers for Disease Control and Prevention—NationalCenterforHealth
Statistics. NCHS-NHIS data from the January-September 2005 National
Health Interview Survey. 2006. Available at: http://www.cdc.gov/nchs/
about/major/nhis/released200603.htm#4. Accessed September 30, 2007.
6. US Department of Health and Human Services. Healthy People 2010 Vol.
1: Understanding and Improving Health and Vol. 2: Objectives for Im-
proving Health. 2nd ed. Washington, DC: US Government Printing Of-
7. Moore RA, Wiffen PJ, Lipsky BA. Are the pneumococcal polysaccharide
vaccines effective? Meta-analysis of the prospective trials. BMC Family
Practice 2000; 1:1.
8. Fisman DN, Abrutyn E, Spaude KA, Kim A, Kirchner C, Daley J. Prior
pneumococcal vaccination is associated with reduced death, complica-
tions, and length of stay among hospitalized adults with community-
acquired pneumonia. Clin Infect Dis 2006; 42:1093-1101.
9. Fedson DS. Hospital-based pneumococcal immunization: the epidemi-
ologic rationale and its implementation. Infect Control 1982; 3:303-308.
10. Shapiro ED, Berg AT, Austrian R, et al. The protective efficacy of pol-
yvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991; 325:
11. McKibben LJ, Stange PV, Sneller VP, Strikas RA, Rodewald LE, Advisory
Committee on Immunization Practices. Use of standing orders programs
to increase adult vaccination rates. MMWR Recomm Rep 2000; 49:15-16.
12. Dexter PR, Perkins SM, Maharry KS, Jones K, McDonald CJ. Inpatient
computer-based standing orders vs physician reminders to increase in-
fluenza and pneumococcal vaccinationrates.JAMA2004; 292:2366-2371.
13. Shefer A, McKibben L, Bardenheier B, Bratzler D, Roberts H. Charac-
teristics of long-term care facilities with standing order programs to
394infection control and hospital epidemiology may 2008, vol. 29, no. 5 Download full-text
deliver influenza and pneumococcal vaccinations toresidentsin13states.
J Am Med Dir Assoc 2005; 6:97-104.
14. Bakare M, Shrivastava R, Jeevanantham V, Navaneethan SD. Impact of
two different models on influenza and pneumococcal vaccination in
hospitalized patients. South Med J 2007; 100:140-144.
15. Honeycutt AA, Coleman MS, Anderson WL, Wirth KE. Cost-effective-
ness of hospital vaccination programs in North Carolina. Vaccine 2007;
16. Sisk J, Moskowitz AJ, Whang W, et al. Cost-effectiveness of vaccination
against pneumococcal bacteremia among elderly people [published cor-
rection appears in JAMA 2000; 283:341]. JAMA 1997; 278:1333-1339.
17. Centers for Medicare and Medicaid Series H. Medicare and Medicaid
programs; conditions of participation: immunization standards for hos-
pitals, long-term care facilities, and home health agencies: final rule with
comment period. Fed Reg 2002; 67:61808-61814.
18. Nowalk MP, Middleton DB, Zimmerman RK, Hess MM, Skledar SJ,
Jacobs MA. Increasing pneumococcal vaccination rates among hospi-
talized patients. Infect Control Hosp Epidemiol 2003; 24:526-531.
19. Skledar SJ, Hess MM, Ervin KA, et al. Designing a hospital-based pneu-
mococcal vaccination program. Am J Health Syst Pharm 2003; 60:1471-
20. Centers for Disease Control and Prevention. Self-reported pneumococcal
race/ethnicity, health-care worker status, and pregnancystatus,UnitedStates,
National Health Interview Survey (NHIS). Available at: http://www.cdc.gov/
September 30, 2007.
21. Husain S, Slobodkin D, Weinstein RA. Pneumococcal vaccination: anal-
ysis of opportunities in an inner-city hospital. Arch Intern Med 2002;
22. Centers for Disease Control and Prevention. Influenza and pneumo-
coccal vaccination coverage among persons aged 1 or p 65 years—
United States, 2004-2005. MMWR Morb Mortal Wkly Rep 2006; 55:1065-
23. Agency for Healthcare Research and Quality. Healthcare Cost & Utili-
zation Project (HCUP). 2003. Available at: http://www.ahrq.gov/data/
hcup/. Accessed September 30, 2007.
24. Lexau CA, Lynfield R, Danila R, et al. Changing epidemiology of invasive
pneumococcal disease among older adults in the era of pediatric pneu-
mococcal conjugate vaccine. JAMA 2005; 294:2043-2051.
25. Weaver M, Krieger J, Castorina J, Walls M, Ciske S. Cost-effectiveness
of combined outreach for the pneumococcal and influenzavaccines.Arch
Intern Med 2001; 161:111-120.
26. Robinson KA, Baughman W, Rothrock G, et al. Epidemiology ofinvasive
Streptococcus pneumoniae infections in the United States, 1995-1998:op-
portunities for prevention in the conjugate vaccine era. JAMA 2001; 285:
27. Gold M, Siegel J, Russell L, Weinstein M. Cost-Effectiveness in Health
and Medicine. New York: Oxford University Press; 1996.
28. HCUP-US Cost-to-Charge Ratio Files. Healthcare Cost and Utilization
Project (HCUP). 2007. Available at: http://www.hcup-us.ahrq.gov/db/
state/costtocharge.jsp. Accessed September 30, 2007.
29. Erickson P, Wilson R, Shannon I. Years of healthy life. Statistical Note
No 7, National Center for Health Statistics. 1995; 7:1-14.
30. Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the
Economic Evaluation of Health Care Programs. 2nd ed. New York: Oxford
University Press; 1997.
31. Sisk JE, Whang W, Butler JC, Sneller VP, Whitney CG. Cost-effectiveness
of vaccination against invasive pneumococcal disease among people 50
through 64 years of age: role of comorbid conditions and race. Ann
Intern Med 2003; 138:960-968.
32. Jackson LA, Benson P, Sneller VP, et al. Safety of revaccination with
pneumococcal polysaccharide vaccine. JAMA 1999; 281:243-248.
33. Laupacis A, Feeny D, Detsky AS, Tugwell PX. How attractive does a new
technology have to be to warrant adoption and utilization? Tentative
guidelines for using clinical and economic evaluations. CMAJ 1992; 146:
34. Mullooly JP, Bennett MD, Hornbrook MC, et al. Influenza vaccination
programs for elderly persons: cost-effectiveness in a health maintenance
organization. Ann Intern Med 1994; 121:947-952.
35. Nichol KL, Margolis KL, Wuorenma J, Von Sternberg TL. The efficacy
and cost effectiveness of vaccination against influenza among elderly
persons living in the community. N Engl J Med 1994; 331:778-784.
36. Rothberg MB, Virapongse A, Smith KJ. Cost-effectiveness of a vaccine
to prevent herpes zoster and postherpetic neuralgia in older adults. Clin
Infect Dis 2007; 44:1280-1288.
37. Hornberger J, Robertus K. Cost-effectiveness of a vaccine to prevent
herpes zoster and postherpetic neuralgia in older adults. Ann Intern Med
38. Centers for Disease Control and Prevention. Adult immunization pro-
grams in nontraditional settings: quality standards and guidance for pro-
gram evaluation. MMWR Morbid Mortal Wkly Rep 2000; 49(RR-01):1-
39. Middleton DB, Fox DE, Nowalk MP, et al. Overcoming barriers to es-
tablishing an inpatient vaccination program for pneumococcus using
standing orders. Infect Control Hosp Epidemiol 2005; 26:874-881.
40. Goldstein AO, Kincade JE, Resnick JE, Gamble G, Bearman RS. Policies
to increase influenza and pneumococcal immunizations in chronically
ill and institutionalized settings. Am J Infect Control 2005; 33:463-468.
41. Sokos D, Skledar S, Ervin K, et al. Designing and implementing a hos-
pital-based vaccine standing orders program. Am J Health Syst Pharm
42. Lindley M, Shefer A, and Shaw F. Assessing state immunization require-
ments for healthcare workers and patients. In: Program and abstracts of
the 40th National Immunization Conference; 2006; Atlanta, GA.
43. Hicks LA, Harrison LH, Flannery B, et al. Incidence of pneumococcal
disease due to non–pneumococcal conjugate vaccine PCV7 serotypes in
the United States during the era of widespread PCV7 vaccination, 1998-
2004. J Infect Dis 2007; 196:1346-1354.
44. Simberkoff MS, Cross AP, Al-Ibrahim M, et al. Efficacy of pneumococcal
vaccine in high-risk patients: results of a Veterans Administration Co-
operative Study. N Engl J Med 1986; 315:1318-1327.
45. Fedson DS. Pneumococcal vaccination in the prevention of community-
acquired pneumonia: an optimistic view of cost-effectiveness.SeminRes-
pir Infect 1993; 8:285-293.
46. Sisk JE, Riegelman RK. Cost effectiveness of vaccination against pneu-
mococcal pneumonia: an update. Ann Intern Med 1986; 104:79-86.
47. Gable CB, Holzer SS, Engelhart L, et al. Pneumococcal vaccine: efficacy
and associated cost savings. JAMA 1990; 264:2910-2915.
48. Patrick KM, Woolley FR. A cost-benefit analysis of immunization for
pneumococcal pneumonia. JAMA 1981; 245:473-477.
49. Willems JS, Sanders CR, Riddiough MA, Bell JC. Cost effectiveness of
vaccination against pneumococcal pneumonia. N Engl J Med 1980; 303:
50. DeGraeve D, Beutels P. Economic aspects of pneumococcal pneumonia:
a review of the literature. Pharmacoeconomics 2004; 22:719-740.
51. DeGraeve D, Lombaert G, Goossens H. Cost-effectiveness analysis of
pneumococcal vaccination of adults and elderly persons in Belgium.
Pharmacoeconomics 2000; 17:591-601.
52. Jackson LA, Neuzil KM, Yu O, et al. Effectiveness of pneumococcal
polysaccharide vaccine in older adults. N Engl J Med 2003; 348:1747-
53. Fine MJ, Smith MA, Carson CA, et al. Efficacy of pneumococcal vac-
cination in adults: a meta-analysis of randomized controlled trials. Arch
Intern Med 1994; 154:2666-2677.
54. Walker FJ, Singleton RJ, Bulkow LR, Strikas RA, Butler JC. Reactions
after 3 or more doses of pneumococcal polysaccharide vaccine in adults
in Alaska. Clin Infect Dis 2005; 40:1730-1735.