Supplemental Appendix
Accompanying the manuscript:
Comparative Evaluation of the Health and Economic Impact of Rotavirus versus
HPV Vaccination in GAVI-Eligible Countries
Sun-Young Kim
Steve Sweet
Joshua Chang
Sue J. Goldie
1
Supplemental Tables and Figures
1. Appendix Table 1: Model Validation: Comparison of outcomes of companion models with
those from more complex models
2. Appendix Table 2: Country-specific results: Health outcomes of rotavirus versus HPV
vaccination in the 72 GAVI-eligible countries (using a single cohort)
3. Appendix Table 3: Country-specific results: Cost-effectiveness of rotavirus versus HPV
vaccination in the 72 GAVI-eligible countries
4. Appendix Table 4: Impact of a 10-year (2010-2019) vaccination with rotavirus versus HPV
vaccines (aggregated across the 72 GAVI-eligible countries)
5. Appendix Figure 1: Age-distribution of averted deaths in the 72 GAVI-eligible countries
6. Appendix Figure 2: Distribution of the incremental cost-effectiveness ratios for rotavirus
versus HPV vaccines by region
2
Appendix Table 1. Model Validation: Comparison of outcomes of companion models with those from more complex models
(a) Comparison with more complex static models, using an example of Vietnam
Rotavirus
Companion model
(used in the present
study)
Key assumptions/analytic choices
Currency and base year
Base year for discounting
Year of intervention
Model type
Time horizon
Main health outcomes
Vaccine type
Strategies
Target population
Vaccination schedule
Coverage (base-case)
Vaccine efficacy (serotype-specific)
Vaccine efficacy adjusted for
serotype distribution?
Serotype distribution (for Vietnam)
HPV
Kim SY et al. [1]
Companion model
(used in the present
study)
Kim JJ et al. [2]
2005 I$
2009
2010
2004 US$
2004
2004
2005 I$
2009
2010
2000 I$
2007
2007
Static cohort model
(implicitly based on a
decision tree)
5 years (ages 0-4)
DALY averted, YLS
Rotarix® or Rotateq®
(non-distinguished)
Markov model
Static cohort model
(implicitly based on a
decision tree)
Lifetime (ages 9-99)
DALY averted, YLS
Gardasil® or Cervarix®
(non-distinguished)
Routine versus no
vaccination
Individual-based Monte
Carlo model
Routine versus no
vaccination
Infants
2,4,6 months
(3 doses)
70%
G1P[8]: 87%
G3P[8]: 90%
G4P[8]: 93%
G9P[8]: 84%
G2P[4], other
combination:71%
Yes
G1P[8]: 44.5%
Strains sharing only
P[8]: 23%
Same
DALY averted, YLS
Rotarix®
Same
Same
2 and 4 months
(2 doses)
94%(dose 1),
93%(dose 2)
G1P[8]: 91%
G3P[8]: 87%
G4P[8]: 87%
G9P[8]: 87%
G2P[4], other
combination:45%
Yes
9-year-old girls
0,1,6 months
(3 doses)
70%
Same
3
Lifetime (ages 9-death)
YLS
Gardasil® or Cervarix®
(non-distinguished)
Routine vaccination, no
vaccination, cervical
cancer screening
9-year-old girls
0,1,6 months
(3 doses)
70% (3 doses)
100% against cervical
cancer caused by HPV
16/18
100% against infection
with HPV 16 and 18
Yes
Yes
70.6%
71.9% (for cancer,
based on data from
neighboring Asian
Duration of vaccine immunity
Waning of vaccine-acquired
immunity
Natural immunity considered
Reinfection considered
Herd immunity considered
Range of costs included
Incidence (rotavirus-associated
deaths or cervical cancer)
Vaccination program costs
Medical utilization for treatment
Strains sharing only
G1: 2.6%
Strains sharing neither
antigen: 26.6%
5 years (ages 0-4)
No
No
No
No
Direct medical costs
(composite program
costs and medical
treatment costs)
5-year cumulative
number of rotavirus
deaths: 1,673 (for a
2004 cohort)
I$25 per vaccinated
individual (vaccine
price: $5 per dose)
1) Rotavirus
gastroenteritis
requiring outpatient
visit: one time
outpatient clinic visit
2) Rotavirus
gastroenteritis
requiring
hospitalization: one
time outpatient visit
plus a 3-day
admission
3) Rotavirus
gastroenteritis
leading to deaths:
one time outpatient
countries)
Same
Yes
Lifetime (ages 9-99)
No
Yes
Yes (up to four)
No
Direct medical costs
plus direct non-medical
costs
No
No
No
Direct medical costs
(composite program
costs and medical
treatment costs)
Age group-specific
(separate data for
Hanoi and Ho Chi Minh
City)
I$25 per vaccinated
individual
Same
Vaccine price: $5 per
dose
Vaccine delivery cost:
$0.7/dose
Same
4
Stage-specific
treatment costs
assume diagnostic
workup, inpatient and
outpatient visits, followup
Lifelong
No (base-case)
Sensitivity analysis:
duration of protection
10-20 years
Yes
Yes
No
Direct medical costs
plus direct non-medical
costs
Age group-specific
(separate data for
Hanoi and Ho Chi Minh
City)
I$10 per vaccinated
individual (varied up to
I$450 per vaccinated
individual)
Stage-specific
treatment costs
assume diagnostic
workup, inpatient and
outpatient visits, followup
Access to care
Cost-effectiveness results
ICERs from original base-case
analyses
visit plus a 3-day
admission
100% for the basecase
(varied in a sensitivity
analysis)
I$ 870/DALY averted
(in 2005 I$)
Same
100% for the basecase
(varied in a sensitivity
analysis)
100%
$540/DALY averted
(in 2004 US$)
I$420/DALY averted*
(in 2005 I$)
Hanoi: dominated [if
cytology is available];
I$650/YLS (in 2000 I$)
[if only HPV screening
is available]
Ho Chi Minh City:
I$30/YLS (in 2000 I$) [if
cytology is available];
I$20/YLS (in 2000 I$) [if
only HPV screening is
available]
Hanoi: I$1,810/YLS (in
2000 I$)**
Ho Chi Minh City:
I$230/YLS (in 2000
I$)**
Hanoi: I$1156/DALY
averted (in 2005 I$)
Ho Chi Minh City:
I$240/DALY averted (in
2005 I$)
ICERs after modifying key model
inputs of the companion models to
closely match the model inputs
used in the complex models
$530/DALY averted
(in 2004 US$)
$540/DALY averted
(in 2004 US$)
Hanoi: I$1,190/YLS (in
2000 I$)**
Ho Chi Minh City:
I$250/YLS (in 2000
I$)**
HPV: human papillomavirus; DALY: disability-adjusted life year; YLS: year of life saved; ICER: incremental cost-effectiveness ratio
* In the present analysis, for the base-case for Vietnam, we report a weighted average, assuming that nearly half of Vietnamese women face the same level of
disease burden as in Hanoi and the other half as in Ho Chi Minh City.
** To improve comparability, we chose to make a comparison based on estimates from sensitivity analyses of Kim JJ et al. paper [34], which includes calculations
of ICERs of vaccination compared to no vaccination (at I$25 per vaccinated girl): I$1810/YLS for Hanoi and I$230/YLS for Ho Chi Minh City.
(b) Comparison with dynamic models, using examples of Kyrgyzstan (Rotavirus) and Brazil (HPV)
Rotavirus
Companion model
(used in the present
study)
Key assumptions/analytic choices
Study setting
GAVI countries
(Kyrgyzstan)
HPV
De Balsio et al. [3]
Kyrgyzstan
5
Companion model
[4]
LAC countries (Brazil)
Kim JJ et al. [5]
Brazil
Currency and base year
Base year for discounting
Year of intervention
2005 I$
2009
2010
NA
2009
2010
2005 I$
2007
2007
2000 I$
2007
2007
Model type
Static cohort model
(implicitly based on a
decision tree)
5 years (ages 0-4)
Dynamic transmission
model
Static cohort model
(implicitly based on a
decision tree)
Lifetime (ages 9-death)
DALY averted, YLS
Rotarix® or Rotateq®
(non-distinguished)
Routine versus no
vaccination
Infants
Case averted
Rotarix® or Rotateq®
(non-distinguished)
Same
2,4,6 months
(3 doses)
70%
2 or 3 doses
Dynamic transmission
model of HPV 16 and
18 infection
Lifetime (ages 12death)
YLS
Gardasil® or Cervarix®
(non-distinguished)
Routine vaccination, no
vaccination
12-year-old girls only
Girls and boys
0,1,6 months
(3 doses)
75%
G1P[8]: 87%
G3P[8]: 90%
G4P[8]: 93%
G9P[8]: 84%
G2P[4], other
combination:71%
Yes
54% against severe
rotavirus infections
100% against cervical
cancer caused by HPV
16/18
100% against infection
with HPV 16 and 18
No
Yes
Yes
NA
68.8%
Not reported
2 months
Yes
Lifetime (ages 9-99)
No
Lifelong
No (base-case)
Sensitivity analysis:
duration of protection
Time horizon
Main health outcomes
Vaccine type
Strategies
Target population
Vaccination schedule
Coverage (base-case)
Vaccine efficacy (serotype-specific)
Vaccine efficacy adjusted for
serotype distribution?
Serotype distribution
Duration of vaccine immunity
Waning of vaccine-acquired
immunity
G1P[8]: 32%
G3P[8]: 4%
G4P[8]: 18%
G9P[8]: 20%
G2P[4], other
combination:26%
5 years (ages 0-4)
No
5 years
Same
95%
6
DALY averted, YLS
Gardasil® or Cervarix®
(non-distinguished)
Routine versus no
vaccination
9-year-old girls
0,1,6 months
(3 doses)
70%
Natural immunity considered
Reinfection considered
Herd immunity considered
Range of costs included
Incidence (rotavirus-associated
deaths or cervical cancer)
Vaccination program costs
Medical utilization
(or medical treatment costs)
Cost-effectiveness results
ICERs from original base-case
analyses
No
No
No
Direct medical costs
(composite program
costs and medical
treatment costs)
5-year cumulative
number of rotavirus
deaths: 465 (for 2004)
I$25 per vaccinated
individual (vaccine
price: $5 per dose)
1)Rotavirus
gastroenteritis
requiring outpatient
visit: one time
outpatient clinic visit
2)Rotavirus
gastroenteritis
requiring
hospitalization: one
time outpatient visit
plus a 3-day
admission
3)Rotavirus
gastroenteritis
leading to deaths:
one time outpatient
visit plus a 3-day
admission
I$ 230/DALY averted
(in 2005 I$)
Yes
Yes
Yes
NA
221 deaths among
children aged <5 years
(for 2009)
NA
No
No
No
Direct medical costs
(composite program
costs and medical
treatment costs)
Age group-specific
I$10-I$50 per
vaccinated individual
NA
Stage-specific
treatment costs
assume diagnostic
workup, inpatient and
outpatient visits, followup
- Stage I: I$3,834
- Stages II-IV:I$3,229
(Health benefits only)
Over 3 years
Deaths averted: 329
Hospitalizations
averted: 5,750
7
(in 2005 I$)
I$10/vaccinated girl
: cost-saving
I$25/vaccinated girl
: I$90/DALY averted
10-20 years
Yes
Yes
Yes
Direct medical costs
plus direct non-medical
costs
Age group-specific
I$25-I$400 per
vaccinated individual
Stage-specific
treatment costs
assume diagnostic
workup, inpatient and
outpatient visits, followup
- Local invasive cancer:
I$5,145
- Regional and
Distance invasive
cancer: I$4,318
(in 2000 I$)
I$25/vaccinated girl
: cost-saving
I$50/vaccinated girl
: I$130/YLS
ICERs after modifying key model
inputs of the companion models to
closely match the model inputs
used in the complex models
(Health benefits only)
Over 3 years
Deaths averted: 283
Hospitalizations
averted: 5,290
Outpatient visits
averted: 31,000
Outpatient visits
averted: 34,000
I$50/vaccinated girl
: I$400/DALY averted
(Health benefits only)
Over 3 years
Deaths averted: 329
Hospitalizations
averted: 5,750
Outpatient visits
averted: 34,000
(in 2000 I$)
I$25/vaccinated girl
: cost-saving
I$50/vaccinated girl
: I$260/YLS
I$100/vaccinated girl
: I$820/YLS
I$400/vaccinated girl
: I$4,190/YLS
I$100/vaccinated girl
: I$740/YLS
I$400/vaccinated girl
: I$3940/YLS
(in 2000 I$)
I$25/vaccinated girl
: cost-saving
I$50/vaccinated girl
: I$130/YLS
I$100/vaccinated girl
: I$740/YLS
I$400/vaccinated girl
: I$3,940/YLS
HPV: human papillomavirus; LAC: Latin America and the Caribbean; DALY: disability-adjusted life year; QALY: quality-adjusted life year; YLS: year of life saved;
ICER: incremental cost-effectiveness ratio.
References
1. Kim S, Goldie SJ, Salomon JA. Cost-effectiveness of rotavirus vaccination in Vietnam. BMC Public Health 2009;9:29.
2. Kim JJ, Kobus KE, Diaz M, O'Shea M, Van Minh H, Goldie SJ. Exploring the cost-effectiveness of HPV vaccination in Vietnam:
insights for evidence-based cervical cancer prevention policy. Vaccine. 2008;26(32):4015-24
3. de Blasio BF, Kasymbekova K, Flem E. Dynamic model of rotavirus transmission and the impact of rotavirus vaccination in
Kyrgyzstan. Vaccine 2010;28:7923-7932.
4. Goldie SJ, Diaz M, Constenla D, Alvis N, Andrus JK, Kim SY. Mathematical models of cervical cancer prevention in Latin
America and the Caribbean. Vaccine. 2008;26(S11):L59-72
5. Kim JJ, Andres-Beck B, Goldie SJ. The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in
a low-resource setting. Br J Cancer 2007;97(9):1322–8.
8
Appendix Table 2. Country-specific results: Health outcomes of rotavirus versus HPV
vaccination in the 72 GAVI-eligible countries (using a single cohort)
Country
AFR D
Angola
Benin
Burkina Faso
Cameroon
Chad
Comoros
Ghana
Guinea
Guinea-Bissau
Liberia
Madagascar
Mali
Mauritania
Niger
Nigeria
Sao Thome
Senegal
Sierra Leone
The Gambia
Togo
AFR E
Burundi
Central African Republic
Congo
Cote d'Ivoire
Democratic Republic of
the Congo
Eritrea
Ethiopia
Kenya
Lesotho
Malawi
Mozambique
Rwanda
Tanzania
Uganda
Zambia
Zimbabwe
AMR A, B, D
Cuba
Guyana
Rotavirus
HPV
Number
of
rotaviru
s deaths
averted
(r=0%)
Rotavirus
deaths
averted
(per 1000
vaccinate
d
children)
DALYs
averted
(r=3%)
Number of
cervical
cancer
deaths
averted
(r=0%)
Cervical
cancer deaths
averted (per
1000
vaccinated
children)
DALYs
averted
(r=3%)
7,384
1,633
3,719
2,636
3,105
45
1,699
1,675
535
1,557
2,541
4,456
386
6,746
29,376
16
1,690
2,639
157
791
14.2
6.7
8.6
6.6
9.8
2.4
3.7
6.9
9.5
12.1
5.2
11.1
5.7
14.4
7.7
4.7
5.8
15.9
4.0
5.0
176,385
42,644
92,836
67,042
76,358
1,245
44,965
43,736
13,602
38,173
68,520
110,369
10,359
160,612
733,421
430
45,473
62,305
4,250
21,192
1,388
1,260
1,061
1,773
1,036
199
2,107
1,394
254
402
4,671
1,327
333
975
8,280
15
613
472
130
660
8
14
7
10
9
24
10
15
14
9
23
10
12
6
6
10
5
8
8
10
6,938
6,023
6,892
8,433
4,194
1,021
9,973
8,562
1,414
2,232
23,881
6,587
1,529
5,574
32,451
65
2,997
2,273
879
3,280
2,689
790
275
3,272
9.3
7.7
3.2
7.6
67,442
19,559
7,180
85,210
1,880
298
384
1,602
22
7
10
9
8,816
1,321
1,739
8,197
21,539
410
16,692
5,088
35
3,245
3,552
2,954
5,808
6,108
2,372
923
10.3
3.1
7.8
5.0
0.9
8.6
6.8
9.9
5.5
6.0
7.8
3.6
541,455
11,263
443,905
132,053
838
81,905
90,101
75,890
146,305
153,907
56,160
21,407
4,853
1,131
16,188
4,885
243
2,798
2,079
2,344
11,287
6,594
2,242
2,365
7
23
19
13
13
18
9
25
27
19
18
20
18,729
5,844
90,553
18,931
1,185
15,106
10,190
10,314
57,742
32,912
11,165
8,287
2
35
0.0
4.8
63
969
570
69
12
12
2,400
455
9
Honduras
Bolivia
Haiti
Nicaragua
EMR D
Afghanistan
Djibouti
Pakistan
Somalia
Sudan
Yemen
EUR B&C
Armenia
Azerbaijan
Georgia
Kyrgyzstan
Tajikistan
Uzbekistan
Moldova
Ukraine
SEAR B&D
Indonesia
Korea, Democratic
Republic R
Sri Lanka
Timor Leste
Bangladesh
Bhutan
India
Myanmar
Nepal
WPR B
Cambodia
Kiribati
Lao People Democratic
Republic
Mongolia
Papua New Guinea
Solomon Islands
Viet Nam
235
456
961
118
1.7
2.6
5.2
1.2
6,710
12,692
26,275
3,384
818
1,275
2,896
1,023
13
16
36
22
3,907
6,754
15,569
5,075
10,785
84
11,479
2,990
2,432
2,469
12.5
5.4
3.5
12.1
2.9
4.0
254,469
2,234
315,915
78,642
65,913
67,530
820
180
5,983
1,885
2,747
996
3
25
5
21
8
4
4,512
873
24,929
9,802
11,668
3,940
32
510
52
284
880
1,472
6
21
1.1
4.7
1.7
3.3
7.1
3.6
0.2
0.1
907
14,086
1,471
7,922
24,217
41,188
159
590
115
204
141
331
280
1,161
141
1,181
11
6
9
10
5
6
10
9
658
1,131
1,018
1,332
1,861
7,105
934
7,257
6,718
2.3
187,993
15,730
11
81,479
464
119
159
8,482
31
64,776
2,894
1,936
2.1
0.6
4.3
3.4
3.8
3.6
4.9
3.5
12,982
3,424
4,470
231,585
858
1,777,110
79,028
52,750
1,316
1,240
108
20,104
84
114,792
4,614
3,735
11
12
9
16
19
14
16
15
6,282
4,995
598
94,762
384
481,097
20,434
17,966
2,295
4
8.6
4.9
63,250
118
2,763
5
25
6
11,324
25
520
83
602
18
910
4.6
2.6
5.0
1.7
0.8
14,067
2,316
16,493
493
26,089
439
170
1,256
111
7,112
9
11
21
25
13
2,227
780
6,776
596
27,291
AFR = African Region; EMR = Eastern Mediterranean Region; EUR = European Region; AMR = Region of the
Americas; WPR = Western Pacific Region; SEAR = South-East Asian Region. DALY = Disability-adjusted life
year.
10
Appendix Table 3. Country-specific results: Cost-effectiveness of rotavirus versus HPV
vaccination in the 72 GAVI-eligible countries
Rotavirus
Country
AFR D
Angola
Benin
Burkina Faso
Cameroon
Chad
Comoros
Ghana
Guinea
Guinea-Bissau
Liberia
Madagascar
Mali
Mauritania
Niger
Nigeria
Sao Thome
Senegal
Sierra Leone
The Gambia
Togo
AFR E
Burundi
Central African Republic
Congo
Cote d'Ivoire
Democratic Republic of
the Congo
Eritrea
Ethiopia
Kenya
Lesotho
Malawi
Mozambique
Rwanda
Tanzania
Uganda
Zambia
Zimbabwe
AMR A, B, D
Cuba
Guyana
Honduras
Bolivia
Haiti
Nicaragua
HPV
ICER
(I$/DALY
averted)
ICER
(I$/DALY
averted)
ICER
(I$/DALY
averted)
ICER
(I$/DALY
averted)
I$10 per
vaccinated child
I$25 per
vaccinated child
I$10 per
vaccinated girl
I$25 per
vaccinated girl
saving
41
25
36
22
132
79
28
14
20
53
17
40
15
31
57
44
6
73
54
40
124
93
122
82
354
228
109
75
69
157
70
136
57
106
169
137
45
209
164
55
46
120
4
178
saving
1
saving
45
82
7
127
saving
217
343
85
233
213
19
43
430
265
445
309
578
99
300
74
236
361
129
424
269
623
1,007
424
816
574
289
339
30
30
96
26
93
106
273
99
63
180
104
47
202
651
416
370
27
102
37
47
413
33
38
12
54
38
33
87
84
273
107
161
1077
100
122
69
159
133
112
259
299
saving
24
71
saving
70
125
saving
44
saving
38
saving
829
115
160
358
153
218
446
103
150
116
203
51
11365
28
146
97
44
247
28477
137
447
296
146
676
70
saving
90
58
13
saving
349
176
324
233
89
120
11
EMR D
Afghanistan
Djibouti
Pakistan
Somalia
Sudan
Yemen
EUR B&C
Armenia
Azerbaijan
Georgia
Kyrgyzstan
Tajikistan
Uzbekistan
Moldova
Ukraine
SEAR B&D
Indonesia
Korea, Democratic
Republic
Sri Lanka
Timor Leste
Bangladesh
Bhutan
India
Myanmar
Nepal
WPR B
Cambodia
Kiribati
Lao People Democratic
Republic
Mongolia
Papua New Guinea
Solomon Islands
Viet Nam
15
42
65
12
94
58
64
143
215
58
276
192
590
saving
383
50
192
497
1,523
92
1,126
185
637
1,344
265
30
163
74
24
5
1795
4847
723
141
461
230
99
150
4528
12192
66
221
82
170
265
194
119
70
301
699
308
543
715
580
348
338
101
323
87
350
138
501
58
73
58
65
43
76
383
1318
178
232
196
212
152
229
101
88
152
56
47
43
37
70
381
384
436
247
216
293
241
266
3
40
64
147
45
284
189
766
43
94
21
168
264
160
292
128
469
870
175
152
19
27
133
497
439
147
136
420
I$ = International dollars; DALY = Disability-adjusted life year; ICER = Incremental cost-effectiveness ratio; AFR
= African Region; EMR = Eastern Mediterranean Region; EUR = European Region; AMR = Region of the
Americas; WPR = Western Pacific Region; SEAR = South-East Asian Region. Incremental cost-effectiveness ratios
are for a strategy of vaccinating 70% of a single birth cohort born in 2010 assuming a vaccination program cost of
I$10 and I$25 per vaccinated child or girl compared to no vaccination.
12
Appendix Table 4. Impact of a 10-year (2010-2019) vaccination with rotavirus versus HPV
vaccines (aggregated across the 72 GAVI-eligible countries)
Target
population
Rotavirus
Number
vaccinated
Year
(million)
(million)
2010
75.8
53.0
2011
76.1
53.3
2012
76.4
53.5
2013
76.6
53.6
2014
76.8
53.8
2015
77.0
53.9
2016
77.1
54.0
2017
77.1
54.0
2018
77.1
54.0
2019
77.1
54.0
Total
767.2
537.0
* Assumed a flat coverage of 70%.
Financial
costs
(2005 US$,
million)
1,108
1,113
1,117
1,121
1,124
1,126
1,128
1,128
1,129
1,128
11,222
13
Target
population
HPV
Number
vaccinated
(million)
32.5
32.8
33.1
33.4
33.7
34.0
34.3
34.6
34.9
35.1
338.3
(million)
22.7
23.0
23.2
23.4
23.6
23.8
24.0
24.2
24.4
24.6
236.8
Financial
Costs
(2005 US$,
million)
466
471
475
480
484
488
493
497
501
505
4,860
Appendix Figure 1: Age-distribution of averted deaths in the 72 GAVI-eligible countries
14
Appendix Figure 2: Distribution of the incremental cost-effectiveness ratios for rotavirus versus HPV vaccines by region
15