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1
Appendix
2
Methods
3
Strategies
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We compared no intervention with 16 single and combination strategies (table 1).
5
Prophylactic strategies included prevaccination before the outbreak of the pandemic,
6
antiviral post-exposure prophylaxis, and school closure. Antiviral targeted prophylaxis
7
(TAP) strategies included household-only prophylaxis (household targeted antiviral
8
prophylaxis [HTAP]), and prophylaxis in the full set of contact groups for an index case
9
(full targeted antiviral prophylaxis [FTAP]). It was assumed that oseltamivir stockpiles of
10
varying quantity are available from the start of a pandemic, ranging from covering 25%
11
of the population (i.e. one pack with 10 capsules per capita for 25% of population) to
12
“unlimited” stockpile (i.e. as much as needed). TAP is carried out by treating identified
13
index cases (the first symptomatic illness in a contact group) and offering prophylaxis
14
only to the contacts of these index cases in close contact groups, namely: households,
15
neighbourhood clusters, large daycare centres, small playgroups, schools, and
16
workgroups. Index cases are therapeutically treated the day after the onset of illness, and
17
prophylaxis of contacts begins at the same time; both are given a single course of
18
oseltamivir. A susceptible individual may receive subsequent courses if exposed to
19
further index cases. We assumed that 60% of symptomatic index cases (i.e. 67% of all
20
infections develop symptoms and 60% of those are ascertained) in households,
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neighbourhood clusters, day care centres, small play groups and workgroups could be
22
ascertained (1), and that all the other members of those groups would receive
23
prophylaxis. For an index case in a school, a random sample of 60% of the close contacts
1
1
of the ill child in the school would receive prophylaxis. (1, 2) We also evaluated a
2
treatment only strategy. Treatment means individuals are adequately treated with
3
oseltamivir, i.e. they start treatment within 48 hours of symptom onset and are compliant.
4
Prevaccination means that 70% of the population is successfully vaccinated with a
5
low-efficacy vaccine before the outbreak of a pandemic. This assumes that prepandemic,
6
low-efficacy vaccine has been stockpiled. Vaccination after the outbreak of the pandemic
7
(or later) was not considered, as it is not a useful strategy if R0 is high. (2)
8
9
We also considered school closure as a measure of social distancing alone, or in
combination with pharmaceutical interventions (prevaccination, TAP). We modelled the
10
impact of closing schools for the duration of the pandemic, or until a well-matched
11
vaccine is available (26 weeks).
12
13
Mathematical model
14
An overview of the disease transmission simulator is shown in Figure A1. The
15
discrete-time stochastic simulator, coded in ANSI C, models influenza natural history,
16
daily infection transmission dynamics (based on an infection probability function) within
17
a structured population, and the effect of the intervention strategies described above,
18
during the first 180 days of an influenza pandemic.
19
The population represents a 1.632 million person city, divided into communities
20
of approximately 2000 people, each of which is further subdivided into four smaller
21
neighbourhoods (Figure A2). The model tracks the number of close contacts that a typical
22
person makes in the course of a day within specified contact groups. Each person is
23
assumed to have daily contacts with household members and with people in the three
24
closest households (neighbourhood cluster), as well as with people in the larger
2
1
neighbourhood and community. The age and approximate household size distributions
2
are matched to those of the US Census 2000 (3). Preschool children attend either small
3
play groups or larger daycare centres, and school-age children attend elementary, middle,
4
or high school, as appropriate. Small play groups have four children each, and there are
5
between 4 and 6 small play groups per neighbourhood. Large daycare centers have, on
6
average, 14 children. School-age children are assigned to either an elementary school,
7
middle school, or high school based on their age. Two neighbourhoods share one
8
elementary school, and all four neighborhoods share a middle and high school.
9
Elementary schools have, on average, 79 children per school, middle schools have an
10
average of 141 students, and high schools have an average of 110 students. Ten percent
11
of high school students attend a high school in a neighboring community. This
12
community structure is similar to that described in previously published reports (1, 2, 4).
13
In addition, sixty-three percent of adults are in workgroups (4) of average size 25.
14
Workgroups are made up of adults from different communities, allowing for transmission
15
of infection from one community to another.
16
Each run of the simulator is seeded with twelve randomly chosen, unvaccinated,
17
initial infectives. Within each contact group, people make contacts sufficient for infection
18
to be transmitted from an infectious to a susceptible person according to the contact
19
probabilities shown in Table A1. These probabilities are based on community
20
transmission parameters discussed by Longini et al. (5), with adjustments made during
21
the calibration of the simulator to achieve a representative basic reproductive number
22
(R0, defined below) for pandemic flu. The probabilities vary by contact group and, in
23
some cases, by the ages of the infectious and susceptible persons. For example, for an
3
1
elementary school child, the relevant contact probabilities are: household contact with a
2
child chcc = 0.2, household contact with an adult chac = 0.3, contact in an elementary
3
school ce = 0.07, contact in the neighborhood cn = 0.00046, and the community, cc =
4
0.00011. The probabilities do not vary over time in our model.
5
Each day, infection of a susceptible person depends on the number of infectious
6
people in the susceptible’s contact groups, on the contact probabilities, and on the
7
probability of transmission given contact, pt, a single probability which can be scaled to
8
represent viruses with different levels of contagiousness or transmissibility. As an
9
example, consider the simplest case that no one is vaccinated. An elementary school child
10
is exposed to the number of child and adult infectives in his household, Ihc and Iha, the
11
infectives in his elementary school, Ie, his neighborhood In, and the community, Ic, with
12
corresponding per-contact infection probabilities for each contact of phcc = chcc∙pt (child to
13
child), phac = chac∙pt (adult to child), pe = ce∙pt, pn = cn∙pt, and pc = cc∙pt, respectively. The
14
probability, P, for that child to become infected on that day is
15
16
17
18
P  1  [(1  phcc ) I hc (1  phac ) I ha (1  pe ) Ie 1  pn  n (1  pc ) Ic ]
I
A uniform [0,1] random number is selected. If the number is less than P, the child
becomes infected.
If exposed people have been given antiviral agents, the per-contact infection
19
probabilities are multiplied by θ, the relative susceptibility, where protective efficacy
20
AVES=1-θ. If an infected person is using an antiviral, then the probability of infection
21
being transmitted from that infected person to a susceptible not using an antiviral is
22
multiplied by φ, the relative infectiousness of infectives. The antiviral efficacy for
23
infectiousness is AVEI=1-φ. If a person using an antiviral agent is infected, then the
4
1
probability that he will become ill is multiplied by ψ, the relative probability of illness
2
given infection. Thus, the antiviral efficacy for illness given infection is AVED=1-ψ. In
3
addition, if a person on antiviral agents does become ill, then his duration of illness is one
4
day less than if he had not taken an antiviral agent. If a person takes an antiviral agent
5
after he is infected, then the AVEI and AVED apply as above, from the time such use
6
begins. For vaccination, we use arguments similar to those above to define vaccine
7
efficacy for susceptibility, VES, and vaccine efficacy for infectiousness, VEI.
8
9
People infected with influenza first pass through a latent and incubation period.
During this period, they do not have influenza symptoms, and they are not infectious until
10
the last day of the period, during which they are half as infectious as they are in the
11
subsequent period, the infectious period. During the infectious period they may develop
12
influenza symptoms. Additionally, the model allows for people to withdraw from all of
13
their mixing groups, except the household, if they become infected. We have set many of
14
the influenza natural history and other transmission parameters of the model according to
15
literature on influenza (6-8), estimates from field studies, and randomized influenza
16
vaccine and antiviral agent trials (11-14). Rather than use fixed values for many of these
17
parameters, we could put prior distributions on them and then use Monte Carlo
18
techniques to add uncertainty about parameters to the simulation output. However, such
19
an approach is prohibitive given the current speed of our simulations.
20
The simulator tracks the infection status of each person in the population each day
21
during each run, and the final infection and illness status of each person is recorded, as
22
are the overall- and age-group-specific illness attack rates. One hundred runs are
23
performed for each scenario, and the results averaged. Larger numbers of runs are not
5
1
feasible, given the complexity of the simulator, the large size of the modeled population
2
and the resulting simulator run-time. However, the authors’ experience with similar
3
simulation models (1, 2, 4, 19) indicates that 100 runs are sufficient to arrive at stable
4
results.
5
Once infected, people follow the clinical pathway as shown in figure 1. If
6
infected, the person may receive treatment, which modifies health outcome (probability
7
of complications, mortality) and resource use (probability of healthcare contact). The
8
epidemiological influenza transmission model determines the proportion of individuals
9
infected with influenza. Stratification of the population by age and risk status is not
10
shown in the simplified clinical pathway, but is accounted for in the model. The age
11
groups were: children 0-4 years, children 5-18 years, younger adults (19-64 years), and
12
older adults (≥65 years). Younger adults are further stratified into high and low risk of
13
complications. High risk adults have underlying chronic conditions (e.g. cardiovascular
14
disease, diabetes, renal disease), which increases their risk for influenza complications
15
and mortality.
The option “prophylaxis” denotes a range of prophylactic interventions, including
16
17
prevaccination before onset of the pandemic, post-exposure TAP with oseltamivir, and
18
school closure. ‘Treatment’ means individuals are effectively treated with oseltamivir, i.e.
19
they start treatment within 48 hours of symptom onset and are compliant.
20
21
Data
22
Basic reproductive number
23
R0 is defined as the average number of secondary infections produced by a typical
24
infected person in a fully susceptible population. (10) To calculate R0, we assumed a
6
1
scenario in which one randomly chosen, unvaccinated, infected person was seeded into a
2
population where everyone else’s ability to transmit was 0. We then counted the number
3
of secondary infections. This was repeated 1000 times. In this way, we generated the
4
whole distribution of secondary cases due to a randomly selected infected person. The
5
mean of this distribution is R0. The calibrated value of the transmission probability was
6
0.15.
7
8
Effectiveness of interventions
9
Prophylaxis—We use current estimates of antiviral efficacy (AVE) of oseltamivir (table
10
2). (11-15) For prophylactic use of oseltamivir, we assumed the relative reduction of the
11
probability of becoming infected given exposure susceptibility to infection (AVES) to be
12
0.30 during a single day of exposure. For both therapeutic and prophylactic use, we
13
assumed the relative reduction of the probability for symptomatic disease given infection
14
(AVED) to be 0.60. Combining the two effects gives the antiviral efficacy for
15
symptomatic disease given exposure (AVESD) of 0.72 (AVESD = 1- [1- AVES][1-
16
AVED]). We assumed the antiviral efficacy for infectiousness (AVEI) to be 0.62. (15)
17
The effect of antiviral agent on people who take it while latent or incubating is the same
18
as the therapeutic effect.
19
For a low-efficacy vaccine, we assumed the vaccine efficacy for susceptibility to
20
infection (VES) to be 0.30, and vaccine efficacy for infectiousness (VEI) to be 0.50. (16)
21
We assumed that two doses of vaccine would be needed. (17)
22
23
Treatment—Oseltamivir effectively reduces incidence of otitis media, bronchitis,
24
pneumonia, influenza-related hospitalisations, and mortality, and improves quality of life.
7
1
(18-21) We assumed that oseltamivir treatment has no impact on the course of illness
2
once otitis media, bronchitis, or pneumonia develops. To calculate probabilities of events
3
when individuals are treated with oseltamivir, we applied the relative reduction in event
4
rates as observed in clinical trials. Treatment with oseltamivir reduces illness by 1 day in
5
the model, and hence also reduces transmission.
6
7
8
Additional sensitivity analysis
It is uncertain whether a pandemic will occur before the shelf life of stockpiled
9
oseltamivir or low-efficacy pandemic vaccine will expire. We therefore considered a
10
scenario where we assumed that a pandemic occurs within the next 33 years. (8) This
11
means oseltamivir and/or low-efficacy vaccine is stockpiled but the chance of a pandemic
12
occurring and the stockpile not being wasted is only 0.33.We assumed complete renewal
13
of the oseltamivir stockpile every 5 years, and the low-efficacy vaccine stockpile every 2
14
years, and calculated the discounted expected costs. Costs and quality adjusted life years
15
(QALYs) are discounted at 3% per annum in line with US guidelines for economic
16
evaluations. (22)
17
Assuming a pandemic occurs within 33 years, and that stockpiles need to be
18
renewed, does not substantially change results. FTAP and prevaccination no longer
19
dominate no intervention because of the increased stockpiling cost. Nevertheless, the
20
ranking of strategies remains otherwise the same, with incremental cost-utility ratios
21
below $46 000 (table A13).
22
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1
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13
Table A1 Contact probability matrix
Children
Pre-school
Contact group
School
Small playgroup
Large daycare
Elementary
Middle
High
Adults
0.35
–
–
–
–
–
Large daycare centres
–
0.25
–
–
–
–
Elementary school
–
–
0.07
–
–
–
Middle school
–
–
–
0.038
–
–
Family
–
–
–
–
0.038
–
Child
0.80
0.80
0.80
0.80
0.80
0.30
Adult
0.30
0.30
0.30
0.30
0.30
0.40
Child
0.20
0.20
0.20
0.20
0.20
0.075
Adult
0.075
0.075
0.075
0.075
0.075
0.10
–
–
–
–
–
0.08
Neighbourhood
0.00032
0.00032
0.00046
0.00046
0.00046
0.0022
Community
0.00008
0.00008
0.00011
0.00011
0.00011
0.00055
Small playgroups
Household cluster
Workgroup
14
Table A2 Probabilities of events
Event
Bronchitis
Pneumonia
Otitis media
Population
Probability of event
Source
Children
0.006
Meier et al, 2000 (23)
Low risk younger adults
0.012
Meier et al, 2000 (23)
High risk younger adults
0.021
Meier et al, 2000 (23)
Older adults
0.030
Meier et al, 2000 (23)
Children
0.002
Meier et al, 2000 (23)
Low risk younger adults
0.003
Meier et al, 2000 (23)
High risk younger adults
0.004
Meier et al, 2000 (23)
Older adults
0.012
Meier et al, 2000 (23)
Children 0-4 years
0.310
Data on file
0.025
Mills et al, 2004 (23)
Death
15
Table A3 QALY Penalties
Event
Influenza
Bronchitis
Pneumonia
Otitis media
Population
QALY penalty
Source
Children
0.010
Assumption: as low risk younger adults
Low risk younger adults
0.010
Data on file
High risk younger adults
0.013
Data on file
Older adults
0.013
Data on file
Children
0.010
Assumption: as influenza
Low risk younger adults
0.010
Assumption: as influenza
High risk younger adults
0.013
Assumption: as influenza
Older adults
0.013
Assumption: as influenza
Children
0.220
Lee et al, 2005 (25)
Low risk younger adults
0.040
Lee et al, 2005 (25)
High risk younger adults
0.040
Lee et al, 2005 (25)
Older adults
0.040
Lee et al, 2005 (25)
Children <5 years
0.250
Prosser et al, 2004 (26)
QALY=quality adjusted life year.
16
Table A4 Resource use
Resou
Event
rce
Populatio
Probability
Probability
Probability
n group
Base Case
Low
High
Source
Units
Units
Units
Base
Low
High
1
3
Source
Case
Physic
Influenza
All
0.75
0.5
1
Assumption
1.4
Assumption
ian
untreated
based on
visit
with
Cox et al,
Oseltamivi
2000 (27)
r
Influenza
All
1
1
1
Assumption
1.4
1
3
Assumption
treated
based on
with
Cox et al,
Oseltamivi
2000 (27)
r
Bronchitis
All
1
0.5
1
Assumption
2.4
1
4
Assumption
Pneumonia
All
1
0.5
1
Assumption
5.7
1
6
Cox et al,
2000 (27)
17
Hospit
Otitis
Children
media
<5 years
Influenza
Children
1
0.5
1
Assumption
3.1
0.0006
0.5 * Base
2 * Base
MMWR, 2000
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
(as influenza)
0.5 * Base
2 * Base
Loughlin et al,
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
(28)
on
Bronchitis
Pneumonia
Antibi
All
All
Otitis
Children
media
<5 years
Influenza
Children
0.0190
0.0006
0.15
0.0006
0.27
otics
Adults
Bronchitis
Children
5
Expert
opinion
alisati
Adults
1
0.28
0.63
18
Cox et al, 2000
(27)
Assumption
Cox et al, 2000
(27)
Assumption
1
2003 (29)
Cox et al, 2000
1
(27)
Loughlin et al,
2003 (29)
1
Adults
0.46
0.5 * Base
2 * Base
Case Value
Case Value
Assumption
1
based on Cox
et al, 2000 (27)
Pneumonia
Children
Adults
Otitis
Children
media
<5 years
OTC
All
medic
0.63
0.36
0.63
1
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
2 * Base
Case Value
Case Value
0.5 * Base
1
Loughlin et al,
1
2003 (29)
Cox et al, 2000
1
(27)
Loughlin et al,
1
2003 (29)
Assumption
1
Case Value
ation
Produ
Caretaker
ctivity
of ill child
Children
2 days/
episode
loss
1
5
Nettleman
et al, 2001
(30)
due to
illness
19
Ill adult
Adults
2 days/
1
5
episode
Meltzer et
al, 1999
(31)
Produ
Household
2.5 days/
ctivity
week
loss
1
5
Nettleman
et al, 2001
(30)
due to
school
closur
e
Teachers
5 days/
Nettleman
and other
week
et al, 2001
professiona
(30)
ls
OTC=over the counter.
20
Table A5 Unit costs
Resource
Oseltamivir
Population groups
All
Unit cost ($)
23.04
Unit
Course of
Source
Data on file
treatment/prophylaxis
Low-efficacy vaccine
All
Low-efficacy vaccine delivery
16.65
Dose
Red Book (32)
9.29
Person vaccinated
Assumption based on Average Medicare
Reimbursement, 2005 (33): in case of
pandemic mass vaccination at a cost of
50% of usual cost
Physician
All
93
Visit
Medicare National Average Allowance
(33)
Influenza hospitalisation
Children
3492
Hospitalisation
Assumption: as bronchitis
Low risk younger adults
3425
Hospitalisation
Assumption: as bronchitis
High risk younger adults
4694
Hospitalisation
Assumption: as bronchitis
Children
3492
Hospitalisation
DRG Handbook, 2006 (34)
Low risk younger adults
3425
Hospitalisation
DRG Handbook, 2006 (34)
and older adults
Bronchitis hospitalisation
21
High risk younger adults
4694
Hospitalisation
DRG Handbook, 2006 (34)
Children
3957
Hospitalisation
DRG Handbook, 2006 (34)
Low risk younger adults
3895
Hospitalisation
DRG Handbook, 2006 (34)
High risk younger adults
6612
Hospitalisation
DRG Handbook, 2006 (34)
and older adults
Pneumonia hospitalisation
and older adults
Otitis media hospitalisation
Children <5 years
2935
Hospitalisation
DRG Handbook, 2006 (34)
Antibiotics
Children
4.12
Course of treatment
Red Book30 (Amoxicillin 500 mg daily
for 5 days)
Adults
8.23
Course of treatment
Red Book (30) (Amoxicillin 1000 mg
daily for 5 days)
OTC medications
All
Productivity loss general
Ill working adult,
population
caretaker of ill child
Productivity loss teachers
Teachers
5.00
Episode
Assumption
923.00
Week
Bureau of Labor Statistics 2006 (35)
931.00
Week
Projections of education statistics to 2015
(36)
Productivity loss other
Other staff working at
professionals
schools
923.00
22
Week
Bureau of Labor Statistics 2006 (35)
Time and travel cost to obtain
Index case
29.00
Household
Calculated based on 20 mile roundtrip
($0.485/mile) and 45 minutes of patient’s
oseltamivir
time
Time and travel cost to obtain
Person vaccinated
14.50
Person vaccinated
vaccine
Assumption: 50% of time and travel cost
to obtain oseltamivir
OTC=over the counter.
23
Table A6 Results (ranked by expected QALYs) for R0=1.6
Illness attack
Deaths
QALYs*
Incremental
Courses
Total cost in
rate (%)
per 1000
per 1000
QALYs† per 1000
per 1000
million $ per 1000
No intervention
34
9
21 227
–
–
0.13
HTAP25
25
5
21 304
77
250
0.10
Treatment only
31
5
21 318
91
–
0.13
HTAP
21
4
21 344
117
395
0.09
HTAP50
21
4
21 345
117
394
0.09
School closure
3.5
0.89
21 407
180
–
2.56
FTAP
0.5
0.09
21 424
197
100
0.003
FTAP25
0.5
0.09
21 424
197
98
0.003
Prevaccination
0.2
0.04
21 426
198
–
0.023
HTAP25 and school closure
0.1
0.02
21 426
199
2
2.56
HTAP and school closure
0.1
0.02
21 426
199
2
2.56
HTAP50 and school closure
0.1
0.02
21 426
199
2
2.56
FTAP50 and school closure
0.05
0.01
21 426
199
4
2.56
FTAP25 and school closure
0.04
0.01
21 426
199
4
2.56
FTAP and school closure
0.04
0.01
21 426
199
4
2.56
Intervention
24
Prevaccination and school
0.02
0.00
21 426
199
–
2.59
0.5
0.09
21 706
479
101
0.006
closure
FTAP50
HTAP=household targeted antiviral prophylaxis; FTAP=full targeted antiviral prophylaxis; QALY=quality adjusted life year.
*Expected average quality adjusted life expectancy; †Compared to no intervention.
25
Table A7. Results (ranked by expected QALYs) for R0=2.0
Total cost in
Illness attack
Deaths
QALYs*
Incremental
Courses
million $
rate (%)
per 1000
per 1000
QALYs† per 1000
per 1000
per 1000
No intervention
52
13
21 129
–
–
0.20
FTAP25
52
13
21 135
6
250
0.20
FTAP50
51
13
21 141
12
500
0.20
HTAP25
50
11
21 173
44
250
0.19
School closure
44
11
21 183
54
–
2.73
HTAP50
46
9
21 222
93
500
0.19
Treatment only
51
9
21 232
103
250
0.20
HTAP25 and school closure
39
9
21 236
107
250
2.72
Prevaccination
31
8
21 242
113
–
0.16
HTAP
42
7
21 258
129
680
0.18
FTAP
26
5
21 304
175
2958
0.14
HTAP50 and school closure
29
5
21 313
184
484
2.70
HTAP and school closure
29
5
21 313
184
483
2.70
FTAP25 and school closure
7
2
21 391
261
250
2.60
Intervention
26
FTAP and school closure
3
1
21 415
286
347
2.59
FTAP50 and school closure
3
1
21 415
286
347
2.59
0.2
0.05
21 425
296
–
2.59
Prevaccination and school closure
HTAP=household targeted antiviral prophylaxis; FTAP=full targeted antiviral prophylaxis; QALY=quality adjusted life year.
*Expected average quality adjusted life expectancy; †Compared to no intervention.
Note: QALY ranking differs from illness attack rate ranking because QALYs take into account the differences in morbidity
and mortality (life expectancy) across age groups, i.e. it is important in which age groups cases and deaths occur.
27
Table A8 Incremental cost-utility for non-eliminated strategies (pandemic occurs within 1 year) for R0=2.0
Total cost in
Incremental
million $
Incremental cost
QALYs†
Incremental
cost-utility
per 1000
per 1000* ($)
per 1000
QALYs per 1000†
ratio*
FTAP
0.14
–
21 304
–
–
FTAP50 and school closure
2.59
2.44
21 415
111
22 037
Prevaccination and school closure
2.59
2.45
21 425
121
20 241
Intervention
FTAP=full targeted antiviral prophylaxis; QALY=quality adjusted life year.
*Compared to FTAP; †Expected average quality adjusted life expectancy.
28
Table A9 Results (ranked by expected QALYs) for mortality=5%
Incremental
Total cost in
Illness attack rate
Deaths
QALYs*
QALYs†
Courses
million $
(%)
per 1000
per 1000
per 1000
per 1000
per 1000
No intervention
50
25
20 864
–
–
0.19
FTAP25
48
24
20 895
31
246
0.18
FTAP50
45
22
20 932
68
481
0.18
HTAP25
48
22
20 943
79
250
0.19
School closure
39
20
20 999
135
–
2.72
HTAP50
42
17
21 059
195
498
0.17
Treatment only
49
17
21 063
199
243
0.20
HTAP
41
14
21 108
244
651
0.17
Prevaccination
26
13
21 122
258
–
0.14
HTAP25 and school closure
31
14
21 123
259
204
2.69
FTAP25 and school closure
23
11
21 178
314
150
2.66
FTAP50 and school closure
22
11
21 197
333
279
2.66
HTAP50 and school closure
27
10
21 209
345
374
2.68
HTAP and school closure
24
9
21 237
373
395
2.67
Intervention
29
FTAP
23
9
21 246
382
2,447
0.12
FTAP and school closure
6
2
21 380
516
640
2.61
Prevaccination and school closure
4
2
21 380
516
–
2.62
HTAP=household targeted antiviral prophylaxis; FTAP=full targeted antiviral prophylaxis; QALY=quality adjusted life year.
*Expected average quality adjusted life expectancy; †Compared to no intervention.
Note: QALY ranking differs from illness attack rate ranking because QALYs take into account the differences in morbidity and mortality
(life expectancy) across age groups, i.e. it is important in which age groups cases and deaths occur.
30
Table A10 Results (ranked by expected QALYs) for work loss for teachers and other staff due to school closure=50%
Incremental
Total cost in
Illness attack rate
Deaths
QALYs*
QALYs†
Courses
million $
(%)
per 1000
per 1000
per 1000
per 1000
per 1000
No intervention
50
13
21 141
–
–
0.19
FTAP25
48
12
21 157
16
246
0.18
FTAP50
45
11
21 175
34
481
0.18
HTAP25
48
11
21 181
40
250
0.19
School closure
39
10
21 210
69
–
2.06
HTAP50
42
8
21 239
98
498
0.17
Treatment only
49
8
21 241
100
243
0.19
HTAP
41
7
21 264
123
651
0.17
Prevaccination
26
6
21 271
130
–
0.14
HTAP25 and school closure
31
7
21 273
132
204
2.04
FTAP25 and school closure
23
6
21 300
159
150
2.00
FTAP50 and school closure
22
5
21 310
169
279
2.00
HTAP50 and school closure
27
5
21 316
175
374
2.02
HTAP and school closure
24
4
21 330
189
395
2.02
Intervention
31
FTAP
23
5
21 351
210
2447
0.12
FTAP and school closure
6
1
21 403
262
640
2.24
Prevaccination and school closure
4
1
21 403
262
–
2.26
HTAP=household targeted antiviral prophylaxis; FTAP=full targeted antiviral prophylaxis; QALY=quality adjusted life year.
*Expected average quality adjusted life expectancy; †Compared to no intervention.
Note: QALY ranking differs from illness attack rate ranking because QALYs take into account the differences in morbidity and mortality
(life expectancy) across age groups, i.e. it is important in which age groups cases and deaths occur.
32
Table A11 Results (ranked by expected QALYs) for low resource use scenario
Incremental
Total cost
Illness attack
Deaths
QALYs*
QALYs†
Courses
in million $
rate (%)
per 1000
per 1000
per 1000
per 1000
per 1000
No intervention
50
13
21 141
–
–
0.09
FTAP25
48
12
21 157
16
246
0.09
FTAP50
45
11
21 175
34
481
0.09
HTAP25
48
11
21 181
40
250
0.10
School closure
39
10
21 210
69
–
1.53
HTAP50
42
8
21 239
98
498
0.10
Treatment only
49
8
21 241
100
243
0.11
HTAP
41
7
21 264
123
651
0.10
Prevaccination
26
6
21 271
130
–
0.08
HTAP25 and school closure
31
7
21 273
132
204
1.53
FTAP25 and school closure
23
6
21 300
159
150
1.51
Intervention
33
FTAP50 and school closure
22
5
21 310
169
279
1.51
HTAP50 and school closure
27
5
21 316
175
374
1.52
HTAP and school closure
24
4
21 330
189
395
1.52
FTAP
23
5
21 351
210
2447
0.08
FTAP and school closure
6
1
21 403
262
640
1.49
4
1
21 403
262
–
1.51
Prevaccination and school
closure
34
Table A12 Results (ranked by expected QALYs) for high resource use scenario
Incremental
Total cost
Illness attack
Deaths
QALYs*
QALYs†
Courses
in million $
rate (%)
per 1000
per 1000
per 1000
per 1000
per 1000
No intervention
50
13
21 141
–
–
0.48
FTAP25
48
12
21 157
16
246
0.46
FTAP50
45
11
21 175
34
481
0.43
HTAP25
48
11
21 181
40
250
0.46
School closure
39
10
21 210
69
–
4.79
HTAP50
42
8
21 239
98
498
0.41
Treatment only
49
8
21 241
100
243
0.46
HTAP
41
7
21 264
123
651
0.39
Prevaccination
26
6
21 271
130
–
0.25
HTAP25 and school closure
31
7
21 273
132
204
4.72
FTAP25 and school closure
23
6
21 300
159
150
4.64
Intervention
35
FTAP50 and school closure
22
5
21 310
169
279
4.63
HTAP50 and school closure
27
5
21 316
175
374
4.68
HTAP and school closure
24
4
21 330
189
395
4.65
FTAP
23
5
21 351
210
2447
0.24
FTAP and school closure
6
1
21 403
262
640
4.48
4
1
21 403
262
–
4.49
Prevaccination and school
closure
36
Table A13 Incremental cost-utility for non-eliminated strategies (pandemic occurs within 33 years)
Total cost in
Incremental
million $
Incremental cost in
QALYs
Incremental QALYs
cost-utility
per 1000
million $ per 1000
per 1000
per 1000
ratio ($)
No Intervention
0.12
–
13 566
–
–
Prevaccination
0.15
0.03
13 649
83
333
FTAP
0.31
0.16
13 700
52
3160
FTAP and school closure
1.80
1.49
13 733
33
45 234
Prevaccination and school closure
1.71
1.39
13 733
33
42 279
Intervention
FTAP=full targeted antiviral prophylaxis; QALY=quality adjusted life year.
37
Table A14 Detailed base case results (ranked by expected QALYs)
QALYs*
Scenario
per 1000
Cost Intervention ($)
Cost Treatment ($)
Cost total ($)
Direct
Indirect
Total
Direct
Indirect
Total
Direct
Indirect
Total
Baseline
21 141
0
0
0
79 352
107 565
186 918
79 352
107 565
186 918
FTAP25
21 157
3 351
575
3 926
75 840
102 941
178 781
79 191
103 516
182 707
FTAP50
21 175
6 612
1 154
7 766
71 139
97 243
168 381
77 751
98 396
176 147
HTAP25
21 181
5 439
2 028
7 467
75 968
104 143
180 111
81 407
106 171
187 578
School Closure
21 210
0
2 563 285
2 563 285
63 908
88 292
152 200
63 908
2 651 577
2 715 485
HTAP50
21 239
10 837
4 158
14 995
66 492
91 902
158 394
77 330
96 059
173 389
Treatment Only
21 241
5 337
7 021
12 358
77 128
105 238
182 365
82 464
112 259
194 723
HTAP
21 264
14 166
5 601
19 767
63 359
87 721
151 079
77 525
93 321
170 846
Vaccination
21 271
22 323
20 214
42 537
39 161
54 462
93 623
61 484
74 676
136 160
HTAP25 and School Closure
21 273
4 469
2 565 097
2 569 566
51 010
71 724
122 733
55 479
2 636 821
2 692 300
FTAP25 and School Closure
21 300
3 380
2 563 918
2 567 298
37 861
51 796
89 656
41 240
2 615 714
2 656 954
38
FTAP50 and School Closure
21 310
6 295
2 564 482
2 570 777
35 489
48 711
84 199
41 784
2 613 193
2 654 976
HTAP50 and School Closure
21 316
8 169
2 566 617
2 574 786
43 158
62 054
105 212
51 327
2 628 671
2 679 998
HTAP and School Closure
21 330
8 632
2 566 815
2 575 447
39 571
57 046
96 617
48 203
2 623 861
2 672 064
FTAP
21 351
35 407
6 944
42 350
33 837
48 127
81 964
69 244
55 071
124 315
FTAP and School Closure
21 403
14 412
2 565 881
2 580 294
9 932
14 691
24 623
24 344
2 580 572
2 604 917
Vaccination and School Closure
21 403
22 323
2 583 500
2 605 823
6 964
10 051
17 015
29 287
2 593 551
2 622 838
HCP=health care payer; FTAP=full targeted antiviral prophylaxis; HTAP=household targeted antiviral prophylaxis, QALY=quality
adjusted life year.
39
Figures
Figure A1 Overview of the disease transmission simulator
40
Figure A2 Schematic representation of social contact structure for one community
41