Abstract
Background:
In Taiwan, two rotavirus vaccines are available on the private market, but are not included in the National Immunization Program (NIP). To help assess whether to include rotavirus vaccines in the NIP, we examined the potential impact and cost-effectiveness of vaccination, from the health care system perspective alone.
Methods:
We used a Microsoft Excel-based model to assess rotavirus vaccination impact on rotavirus disease burden and the cost-effectiveness of 2-dose and 3-dose vaccination programs among a birth cohort of Taiwanese children followed for 5 years. Principal model inputs included data on rotavirus disease burden and related healthcare costs, vaccination cost and coverage rates, and vaccine efficacy. Principal model outputs included the number of health-related events and costs averted and incremental cost per disability-adjusted life year averted.
Results:
A national rotavirus vaccination program, regardless of number of doses per course, would prevent 4 deaths, >10,500 hospitalizations, and >64,000 outpatient visits due to rotavirus infection among children <5 years annually, resulting in ~80%, 90%, and 70% declines in these outcomes, respectively, and a ~$7 million decline in annual medical costs. A national 2- or 3-dose vaccination program would be cost-saving up to $13.30 per dose ($26.60 per course) or $7.98 per dose ($23.94 per course), respectively; very cost-effective up to $24.08 per dose ($48.16 per course) or $15.18 per dose ($45.54 per course), respectively; and cost-effective up to $45.65 per dose ($91.30 per course) or $29.59 per dose ($88.77 per course), respectively.
Conclusions:
A national rotavirus vaccination program could substantially reduce rotavirus disease burden among Taiwanese children and be potentially cost-effective, depending on the vaccine price.
Keywords: gastroenteritis, rotavirus, rotavirus vaccine, cost-effectiveness
INTRODUCTION
Rotavirus is the leading cause of severe gastroenteritis among young children worldwide, accounting for ~23 million outpatient visits, 2.3 million hospitalizations, and nearly half a million deaths annually among children under 5 years of age [1–3]. In Taiwan, rotavirus infection accounts for a substantial proportion of gastroenteritis hospitalizations among children under 5 years of age – approximately 25% to 43% annually, with the majority of rotavirus hospitalizations occurring by the age of 3 years [4–7]. Because of this substantial burden of disease, two orally administered, live, attenuated rotavirus vaccines, Rotarix® (2-dose vaccine; GSK Biologicals, Rixensart, Belgium) and RotaTeq® (3-dose vaccine; Merck & Co., Inc., Pennsylvania, USA), were licensed for use in Taiwan in August 2006. Neither vaccine is publically funded, so parents must pay out of pocket to vaccinate their children. Current rotavirus vaccines prices in Taiwan are ~$172 for a 2-dose course of Rotarix (i.e., ~$86 per dose) and ~$200 for a 3-dose course of RotaTeq (i.e., ~$67 per dose). An analysis of the potential cost-effectiveness of a national rotavirus vaccination program will provide policymakers with useful information to assess whether rotavirus vaccines should be included in the National Immunization Program, as has been recommended by the World Health Organization (WHO) since 2009 [8].
The objective of this study was to provide an evaluation of the impact of a rotavirus vaccination program on rotavirus disease burden and to determine the potential cost-effectiveness from the healthcare perspective of a national vaccination program using the most up-to-date data available on vaccine efficacy among Taiwanese infants and diarrhea-related medical visits in Taiwan.
METHODS
Model Overview
We used a Microsoft Excel-based model that has been used in previous rotavirus vaccine cost-effectiveness studies to assess the impact of rotavirus vaccination on rotavirus disease burden and to evaluate the cost-effectiveness of a national vaccination program following a hypothetical birth cohort of Taiwanese children until the age of five years [9–11]. Since both currently licensed rotavirus vaccines are available on the private market in Taiwan, the model was modified to create two separate analyses to assess a 2-dose vaccination program (similar to Rotarix) and a 3-dose vaccination program (similar to RotaTeq).
Principal model inputs included information on rotavirus disease burden, healthcare utilization and costs related to rotavirus disease treatment, vaccination cost and coverage rates, and vaccine effectiveness. Principal model outputs included impact of vaccination on rotavirus disease burden, expressed as the number of health-related events and costs averted, and cost-effectiveness of a national vaccination program, expressed as incremental cost per disability-adjusted life year (DALY) and incremental cost per death averted. DALYs quantify years of healthy life lost due to disability and premature mortality [12].
Model Inputs
Rotavirus disease burden
Disease burden inputs included rotavirus-related mortality, hospitalization, and outpatient visit rates. We obtained data from pre-rotavirus vaccine introduction years 2000 to 2005 on the number of diarrhea-related deaths and from 2005 on the number of diarrhea-related hospitalizations and outpatient visits, which included clinic visits and Emergency Department visits, among children under 5 years of age from the National Health Insurance Research Databases (NHIRD). The NHIRD contain health utilization and cost data for approximately 99% of the population since health care is provided through a national health insurance program. We defined a diarrhea-associated health visit as one associated with any of the following International Classification of Diseases, Ninth Edition (ICD-9) codes: 001 (cholera), 002 (typhoid and paratyphoid fever), 003 (salmonellosis), 004 (shigellosis), 005 (other bacterial food poisoning), 006 (amoebiasis), 007 (other protozoan intestinal diseases), 008 (intestinal infections due to other organisms), 009 (ill-defined intestinal infections), 558.9 (other and unspecified noninfectious gastroenteritis and colitis), and 787.91 (diarrhea). We excluded visits with the following codes: 003.2 (Localized salmonella infections), 006.3 (localized salmonella infections: amoebic liver abscess: hepatic amoebiasis), 006.4 (amoebic lung abscess), 006.5 (amoebic abscess of lung and liver), and 006.6 (amoebic skin ulceration).
The diarrhea mortality rate was estimated by averaging annual diarrhea-related death rates, defined as the number of diarrhea hospitalizations with a discharge status of “dead” divided by the annual population census, for 2000–2005. The diarrhea hospitalization rate was calculated by dividing the number of diarrhea-related hospitalizations for 2005 by the 2005 population census. To obtain rotavirus-specific mortality and hospitalization rates, we applied the mean detection proportion of rotavirus-positive gastroenteritis hospitalizations among children under 5 years of age from previously published rotavirus surveillance studies from Taiwan to the diarrhea mortality and hospitalization rates (Table 1) [4, 5, 7]. For all calculations, we took into account the age distribution for all outcomes using data from the NHIRD. Since similar rotavirus detection rates were unavailable for outpatient visits, we first calculated the diarrhea-related outpatient visit rate using data from the NHIRD and then calculated the rotavirus-specific outpatient rate using a previously published method in which the rate of rotavirus outpatient visits was estimated to be 8 times that of hospitalizations [2].
Table 1.
Principle base-case values, sensitivity ranges, and references
| Parameter | Base-case estimate | Sensitivity range | References |
|---|---|---|---|
| Disease burden (per 100,000 children <5 yrs) | |||
| Rotavirus death rate | 0.49 | 0.36–0.62 | NHIRD;[4, 5, 7] |
| Rotavirus hospitalization rate | 1,113 | 818–1407 | NHIRD;[4, 5, 7] |
| Rotavirus outpatient visit rate | 8,904 | 6,546–11,258 | NHIRD;[2, 4, 5, 7] |
| Treatment costs (2005 $) | |||
| Cost of average hospitalization | $507.98 | $380.99–$634.98 | NHIRD |
| Cost of average outpatient visit | $29.27 | $21.95–$36.59 | NHIRD |
| Vaccine performance (2-dose analysis/3-dose analysis) | |||
| Efficacy against deatha, % | 96.1/98 | 86.1–100/88–100 | [17]/[18] |
| Efficacy against hospitalization, % for <1 yr/1–2 yrs | 96.1/98 | 86.1–100/88–100 | [17]/[18] |
| Efficacy against outpatient visitb, % for <1 yr/1–2 yrs | 86/88 | 76–96/88–98 | [17]/[18] |
| Partial dose effectivenessc, % | 50/33, 66 | —— | [13–15] |
| Vaccine coverage | |||
| First dose, % | 98.1 | 88.1–100 | TW CDC NIIS |
| Second dose, % | 97.8 | 87.8–100 | TW CDC NIIS |
| Third dose, % | 96 | 86–100 | TW CDC NIIS |
NHIRD: National Health Insurance Research Databases, Taiwan
TW CDC NIIS: Taiwan CDC National Immunization Information System
Same efficacy as efficacy again hospitalization.
Efficacy 10 % points lower than efficacy against hospitalization.
Partial dose effectiveness against rotavirus-related deaths, hospitalizations, and outpatient visits by using a 1 dose estimate of 50% for the 2-dose analysis and a 1 dose estimate of 33% and 2 dose estimate 66% for the 3-dose analysis.
We also used disability adjusted life years (DALYs), which estimate the number of years lost due to premature death and number of years lived with a disability, to quantify disease burden. DALY estimates included age weights and were discounted at a rate of 3%.
Rotavirus treatment costs
We obtained average hospitalization and outpatient visit costs also from the NHIRD. All costs are presented in 2005 US dollars and were discounted at an annual rate of 3%.
Rotavirus vaccination effectiveness
Clinical trials have demonstrated varying vaccine efficacy in countries of different income levels. Therefore, for the 2-dose vaccination program analysis, we applied Rotarix vaccine efficacy data from a clinical trial conducted in Hong Kong, Singapore, and Taiwan for our rotavirus vaccine effectiveness estimates. Data from these three countries demonstrated a vaccine efficacy against severe rotavirus gastroenteritis of 96.1% [13]. Since no RotaTeq vaccine efficacy data are available from Taiwan or other similar Asian countries, we applied a vaccine efficacy against severe rotavirus gastroenteritis of 98%, as was seen in the clinical trials conducted in the US and Europe, for the 3-dose vaccination program analysis [14]. Of note, these vaccine efficacy estimates are similar to the vaccine effectiveness estimates obtained for a post-licensure study in Taiwan (unpublished data). For each analysis, we applied the same vaccine effectiveness estimate against severe rotavirus gastroenteritis to rotavirus-related deaths, and we assumed that effectiveness was 10 percentage points lower for less severe rotavirus gastroenteritis resulting in outpatient visits, similar to what was seen in the RotaTeq trial conducted in the US and Europe [14]. We accounted for partial dose effectiveness against rotavirus-related deaths, hospitalizations, and outpatient visits by using a 1 dose estimate of 50% for the 2-dose vaccination program analysis and a 1 dose estimate of 33% and 2 dose estimate 66% for the 3-dose vaccination program analysis [9–11].
Rotavirus vaccination coverage and timing
Assuming a 2-dose rotavirus vaccine course administered on time and on the same schedule of 2 and 4 months of age as the first two doses of diphtheria, tetanus, and pertussis (DTP) vaccine and a 3-dose rotavirus vaccine course administered on time and on the same schedule of 2, 4, and 6 months of age as the first three doses of DTP vaccine, we used 2005 vaccination coverage rates of 98.1%, 97.8%, and 96% for DTP doses 1, 2, and 3, respectively, to approximate rotavirus vaccination coverage.
Rotavirus vaccination cost
Rotavirus vaccination cost includes cost of vaccine, administration costs, and wastage. Currently in Taiwan, the price of a 2-dose course of Rotarix is ~$172 (i.e., ~$86 per dose), while the price of a 3-dose course of RotaTeq is ~$200 (i.e., ~$67 per dose). Since the exact administration cost of rotavirus vaccine in current use was not known, we assumed it to be $3 per dose according to the outpatient clinic registration fees. We also applied a vaccine wastage rate of 10%.
Model Outputs
Model outputs related to vaccination output and cost-effectiveness were assessed in the same manner for each analysis (i.e., 2-dose vaccination program and 3-dose vaccination program).
Vaccination impact
We examined rotavirus vaccination impact on rotavirus disease burden by determining the number of rotavirus-related deaths, hospitalizations, and outpatient visits and related costs averted annually.
Cost-effectiveness
We examined the potential cost-effectiveness of a rotavirus vaccination program by calculating the incremental cost-effectiveness ratio (ICER) in 2005 US dollars ($). For this, we calculated both the incremental cost per DALY averted and the incremental cost per death averted; all costs and savings focused on direct medical treatment costs. According to the WHO, an intervention is “very cost-effective” if the ICER is below the per capita gross domestic product (GDP) of a country and “cost-effective” if the ICER is below three times the per capita GDP. In Taiwan, the 2005 per capita GDP was $16,449.
Sensitivity Analyses
We performed one-way sensitivity analyses to determine lower and upper range estimates for the incremental cost per DALY averted and the incremental cost per death averted. To do this, we individually varied each base-case model input and noted the effect on the cost-effectiveness measurements (Table 4). We varied mortality, hospitalization, and outpatient rates using the lower (25%, 25%, and 14%, respectively) and upper (43%, 43%, and 24%, respectively) ranges for rotavirus detection among hospitalized children from prior rotavirus surveillance studies and varied hospitalization costs, outpatient visit costs, administration costs by ±25%.
Table 4.
Taiwan rotavirus vaccine cost-effectiveness analysis – sensitivity analysis for 2-dose programa
| $10 per dose | $20 per dose | $40 per dose | ||||||
|---|---|---|---|---|---|---|---|---|
| Input | Value | Change, % | $ per DALY averted | Change in ICER | $ per DALY averted | Change in ICER | $ per DALY averted | Change in ICER |
| Proportion of diarrhea deaths, hospitalizations, outpatient visits due to rotavirus | ||||||||
| Low | 25, 25, 14 | −26 | 1,949 | −139% | 22,691 | 122% | 64,174 | 58% |
| Base case | 34, 34, 19 | −5,039 | 10,212 | 40,715 | ||||
| High | 43, 43, 24 | 26 | −9,102 | 81% | 2,957 | −71% | 27,076 | −33% |
| Rotavirus death rate per 100,000 | ||||||||
| Low | 0.36 | −26 | −5,719 | 13% | 11,737 | 15% | 46,793 | 15% |
| Base case | 0.49 | −5,039 | 10,212 | 40,715 | ||||
| High | 0.62 | 26 | −4,460 | −11% | 9,038 | −11% | 36,034 | −11% |
| Rotavirus hospitalization rate per 100,000 | ||||||||
| Low | 818 | −26 | −432 | −91% | 14,865 | 46% | 45,458 | 12% |
| Base case | 1,113 | −5,039 | 10,212 | 40,715 | ||||
| High | 1,407 | 26 | −9,619 | 91% | 5,587 | −45% | 36,000 | −12% |
| Rotavirus outpatient rate per 100,000 | ||||||||
| Low | 6,546 | −26 | −3,658 | −27% | 13,910 | 36% | 49,045 | 20% |
| Base case | 8,904 | −5,039 | 10,212 | 40,715 | ||||
| High | 11,258 | 26 | −6,098 | 21% | 7,376 | −28% | 34,326 | −16% |
| Hospitalization cost per child, $ | ||||||||
| Low | 380.99 | −25 | −687 | −86% | 14,565 | 43% | 45,067 | 11% |
| Base case | 507.98 | −5,039 | 10,212 | 40,715 | ||||
| High | 634.98 | 25 | −9,392 | 86% | 5,860 | −43% | 36,362 | −11% |
| Outpatient cost per child, $ | ||||||||
| Low | 21.95 | −25 | −3,279 | −35% | 11,972 | 17% | 42,475 | 4% |
| Base case | 29.27 | −5,039 | 10,212 | 40,715 | ||||
| High | 36.59 | 25 | −6,799 | 35% | 8,452 | −17% | 38,955 | −4% |
| Vaccine efficacy against death, % | ||||||||
| Low | 86.1 | −10 | −5,310 | 5% | 10,762 | 5% | 42,906 | 5% |
| Base case | 96.1 | −5,039 | 10,212 | 40,715 | ||||
| High | 100 | 10 | −4,941 | −2% | 10,013 | −2% | 39,920 | −2% |
| Vaccine efficacy against hospitalization, % | ||||||||
| Low | 86.1 | −10 | −3,251 | −35% | 12,113 | 19% | 42,843 | 5% |
| Base case | 96.1 | −5,039 | 10,212 | 40,715 | ||||
| High | 100 | 10 | −5,279 | 14% | 9,478 | −7% | 39,893 | −2% |
| Vaccine efficacy against outpatient, % | ||||||||
| Low | 76.1 | −10 | −4,448 | −12% | 11,621 | 14% | 43,760 | 7% |
| Base case | 86.1 | −5,039 | 10,212 | 40,715 | ||||
| High | 96.1 | 10 | −5,573 | 11% | 8,940 | −12% | 37,964 | −7% |
| Administration cost per dose, $ | ||||||||
| Low | 2.25 | −25 | −6,079 | 21% | 9,172 | −10% | 39,675 | −3% |
| Base case | 3.00 | −5,039 | 10,212 | 40,715 | ||||
| High | 3.75 | 25 | −3,999 | −21% | 11,252 | 10% | 41,755 | 3% |
Analysis for changes in coverage rates now shown since % change was <1 in all cases
For vaccine effectiveness inputs, we varied effectiveness against deaths, hospitalizations, outpatient visits by ±10 percentage points (maximum effectiveness 100%). For vaccine coverage rates, we varied DTP dose coverage by ±10 percentage points (maximum coverage 100%).
RESULTS
Rotavirus Disease Burden and Treatment Costs
Rotavirus-related deaths occurred at a rate of approximately 0.49 per 100,000 children under 5 years of age. Rotavirus-related hospitalizations and outpatient visits occurred at rates of approximately 1,113 and 8,904 per 100,000 children under 5 years of age, respectively (Table 1). Based on 2005 data, we calculated average costs of $507.98 for each rotavirus-related hospitalization (average length of stay: ~5 days) and $29.27 for each rotavirus-related outpatient visit (Table 1).
Rotavirus Vaccination Impact
Based on the 2005 birth cohort of 205,854 Taiwanese children and the estimated mortality, hospitalization, and outpatient visit rates attributable to rotavirus infection, we estimate that a national 2-dose rotavirus vaccination program would prevent 4 deaths, 10,571 hospitalizations, and 65,228 outpatient visits due to rotavirus-related diarrhea among children under 5 years of age annually, resulting in 291 DALYs averted (Table 2). This translates to 83%, 92%, and 72% declines in rotavirus-related deaths, hospitalizations, and outpatient visits, respectively. A national 3-dose rotavirus vaccination program would prevent 4 deaths, 10,534 hospitalizations, and 64,938 outpatient visits, resulting in 290 DALYs averted and translating to 81%, 92%, and 71% declines in rotavirus-related deaths, hospitalizations, and outpatient visits, respectively.
Table 2.
Rotavirus-related events in children <5 years of age and associated medical treatment costs, with, without, and averted by a 2- or 3-dose rotavirus vaccination program, Taiwan 2005
| Variable | Without vaccine | 2-dose vaccination program | 3-dose vaccination program | ||
|---|---|---|---|---|---|
| With vaccine | Annual averted events or costs (%) | With vaccine | Annual averted events or costs (%) | ||
| Number of events | |||||
| Deaths | 5 | 1 | 4(83) | 1 | 4(81) |
| Hospitalizations | 11,465 | 894 | 10,571(92) | 931 | 10,534(92) |
| Outpatient visits | 90,891 | 25,663 | 65,228(72) | 26,052 | 64,938(71) |
| DALYs lost | 351 | 60 | 291(83) | 61 | 290(81) |
| Medical treatment costs, in millions, $ | |||||
| Hospitalization | 5.5 | 0.4 | 5.1(92) | 0.6 | 4.9(90) |
| Outpatient | 2.5 | 0.5 | 2.0(81) | 0.5 | 2.0(79) |
| Total | 8.0 | 0.9 | 7.1(89) | 1.1 | 6.9(87) |
Regarding rotavirus treatment costs, a national 2-dose rotavirus vaccination program has the potential to reduce annual medical costs related to hospitalization and outpatient care by $5.1 million and $2 million, respectively, for a total reduction of $7.1 million (Table 2). This translates to an 89% reduction in medical treatment costs related to rotavirus infection. A national 3-dose rotavirus vaccination program has the potential to reduce annual medical costs related to hospitalization and outpatient care by $4.9 million and $2 million, respectively, for a total reduction of $6.9 million, resulting in an 87% reduction in medical treatment costs related to rotavirus infection.
Rotavirus Vaccination Cost-Effectiveness
The medical breakeven price of a national 2-dose rotavirus vaccination program is $13.30 per dose ($26.60 per course) (Table 3). A 2-dose vaccination program would be very cost-effective according to WHO standards up to $24.08 per dose ($48.16 per course) at a program cost of $11.9 million and cost-effective up to $45.65 per dose ($91.30 per course) at a program cost of $21.5 million.
Table 3.
Cost-effectiveness of a 2- or 3-dose rotavirus vaccination program at varying vaccine dose prices, Taiwan
| Vaccine price per dose | Cost of program in millions, $ | Net cost in millions, $ | Incremental cost per DALY averted, $ | Incremental cost per death averted, $ |
|---|---|---|---|---|
| 2-dose program | ||||
| $10.00a | 5.6 | −1.5 | −5039 | −350,131 |
| $13.30b | 7.1 | 0 | 0 | 0 |
| $20.00c | 10.1 | 3.0 | 10,212 | 709,588 |
| $40.00d | 19.0 | 11.8 | 40,715 | 2,829,025 |
| $60.00 | 27.8 | 20.7 | 71,217 | 4,948,463 |
| 3-dose program | ||||
| $7.98b | 7.1 | 0 | 0 | 0 |
| $10.00c | 8.4 | 1.3 | 4,614 | 320,273 |
| $20.00d | 15.0 | 7.9 | 27,443 | 1,904,769 |
| $40.00 | 28.2 | 21.2 | 73,102 | 5,073,859 |
| $60.00 | 41.5 | 34.4 | 118,761 | 8,242,949 |
Vaccination program cost-saving and very cost-effective
Break-even price; vaccination program very cost-effective
Vaccination program very-cost effective
Vaccination program cost-effective
The medical breakeven price of a national 3-dose rotavirus vaccination program is $7.98 per dose ($23.94 per course) (Table 3). A 3-dose vaccination program would be very cost-effective according to WHO standards up to $15.18 per dose ($45.54 per course) at a program cost of $11.8 million and cost-effective up to $29.59 per dose ($88.77 per course) at a program cost of $21.4 million.
At current market prices of $86 per dose for a 2-dose vaccine and $67 per dose for a 3-dose vaccine, a vaccination program would not be cost effective.
Sensitivity Analyses
For both 2-dose and 3-dose vaccination program analyses, the ICER was most sensitive to changes in rotavirus disease burden estimates and hospitalization costs (Tables 4 and 5). At $10 per vaccine dose, both vaccination programs remained very cost-effective despite large fluctuations in the ICER with the upper and lower limits of disease burden estimates and hospitalization costs. With changes in all inputs at $20 per vaccine dose, the 2-dose vaccination program remained very cost-effective (except with the lower limits of rotavirus detection in diarrheal deaths, hospitalizations, and outpatient visits for which the vaccination program became cost-effective) (Table 4) and the 3-dose vaccination program remained cost-effective (Table 5). With changes in all inputs at $40 per vaccine dose, the 2-dose vaccination program, which was originally cost-effective, was no longer cost-effective when the lower limits of rotavirus detection were examined, while the 3-dose vaccination program remained not cost-effective.
Table 5.
Taiwan rotavirus vaccine cost-effectiveness analysis – sensitivity analysis for 3-dose programa
| $10 per dose | $20 per dose | $40 per dose | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Input | Value | Change, % | $ per DALY averted | Change in ICER | $ per DALY averted | Change in ICER | $ per DALY averted | Change in ICER | ||||
| Proportion of diarrhea deaths, hospitalizations, outpatient visits due to rotavirus | ||||||||||||
| Low | 25, 25, 14 | −26 | 15,704 | 240% | 46,122 | 68% | 108,218 | 48% | ||||
| Base case | 34, 34, 19 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 43, 43, 24 | 26 | −1,468 | −132% | 16,583 | −40% | 52,686 | −28% | ||||
| Rotavirus death rate per 100,000 | ||||||||||||
| Low | 0.36 | −26 | 5,303 | 15% | 31,545 | 15% | 84,028 | 15% | ||||
| Base case | 0.49 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 0.62 | 26 | 4,083 | −12% | 24,285 | −12% | 64,690 | −12% | ||||
| Rotavirus hospitalization rate per 100,000 | ||||||||||||
| Low | 818 | −26 | 9,251 | 100% | 32,148 | 17% | 77,941 | 7% | ||||
| Base case | 1,113 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 1,407 | 26 | 3 | −100% | 22,766 | −17% | 68,292 | −7% | ||||
| Rotavirus outpatient rate per 100,000 | ||||||||||||
| Low | 6,546 | −26 | 7,456 | 62% | 33,749 | 23% | 86,336 | 18% | ||||
| Base case | 8,904 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 11,258 | 26 | 2,433 | −47% | 22,605 | −18% | 62,949 | −14% | ||||
| Hospitalization cost per child, $ | ||||||||||||
| Low | 380.99 | −25 | 8,968 | 94% | 31,797 | 16% | 77,456 | 6% | ||||
| Base case | 507.98 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 634.98 | 25 | 260 | −94% | 23,089 | −16% | 68,748 | −6% | ||||
| Outpatient cost per child, $ | ||||||||||||
| Low | 21.95 | −25 | 6,370 | 38% | 29,200 | 6% | 74,859 | 2% | ||||
| Base case | 29.27 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 36.59 | 25 | 2,857 | −38% | 25,687 | −6% | 71,346 | −2% | ||||
| Vaccine efficacy against death, % | ||||||||||||
| Low | 86.1 | −10 | 4,857 | 5% | 28,891 | 5% | 76,960 | 5% | ||||
| Base case | 96.1 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 100 | 10 | 4,568 | −1% | 27,171 | −1% | 72,377 | −1% | ||||
| Vaccine efficacy against hospitalization, % | ||||||||||||
| Low | 86.1 | −10 | 6,438 | 40% | 29,434 | 7% | 75,427 | 3% | ||||
| Base case | 96.1 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 100 | 10 | 3,634 | −8% | 27,048 | −1% | 72,641 | −1% | ||||
| Vaccine efficacy against outpatient, % | ||||||||||||
| Low | 76.1 | −10 | 5,695 | 23% | 29,720 | 8% | 77,768 | 6% | ||||
| Base case | 86.1 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 96.1 | 10 | 3,634 | −21% | 25,382 | −8% | 68,878 | −6% | ||||
| Administration cost per dose, $ | ||||||||||||
| Low | 2.25 | −25 | 3,057 | −34% | 25,887 | −6% | 71,546 | −2% | ||||
| Base case | 3.00 | 4,614 | 27,443 | 73,102 | ||||||||
| High | 3.75 | 25 | 6,170 | 34% | 29,000 | 6% | 74,659 | 2% | ||||
Analysis for changes in coverage rates now shown since % change was <1 in all cases
DISCUSSION
Our analysis demonstrates that a national rotavirus vaccination program in Taiwan, regardless of a 2-dose or 3-dose course, has the potential to avert a substantial number of rotavirus-related deaths, hospitalizations, and outpatient visits annually among Taiwanese children under 5 years of age and to result in ~$7 million in annual medical treatment costs savings.
According to our estimates, without a rotavirus vaccination program, approximately 1 in 20 children will be hospitalized and 1 in 2 children will require an outpatient visit for rotavirus gastroenteritis by the age of 5 years. These estimates are much greater than those for the United States where, prior to introduction of rotavirus vaccination, approximately 1 in 70 children were hospitalization with rotavirus gastroenteritis and 1 in 7 children required outpatient care by the age of 5 years [15, 16]. With a rotavirus vaccination program, we estimate that the number of rotavirus-related hospitalizations and outpatient visits would decrease substantially by ~90% and ~70%, respectively.
Such large declines in hospitalizations and outpatients visits not only would impact medical treatment costs, but also non-medical and societal costs usually incurred when a child becomes ill, such as food and transportation costs and wages lost by parents due to time off from work to care for their ill child. Prior studies conducted in Taiwan have demonstrated non-medical and societal costs of greater than ~$150 per hospitalization [17–20], and preliminary data from a rotavirus hospitalization cost study conducted from 2009–2011 by the Taiwan Centers for Disease Control, the Taiwan National Health Research Institutes, and three sentinel surveillance hospitals (the Chang Gung Memorial Hospital in Linkou, the Changhua Christian Hospital in Taichung and the Chang Gung Memorial Hospital in Kaohsiung) indicate that non-medical and indirect costs related to rotavirus hospitalization treatment may be greater than $130 per hospital stay (unpublished data). Therefore, there are likely to be substantial non-medical and societal cost savings that our study has not included, resulting in an underestimation of the potential cost savings of a national vaccination program.
Our study also was limited by the fact that we could not account for potential indirect benefits of rotavirus vaccination among older age groups, as has been suggested to occur by previously published vaccine impact studies [21–27]. Any potential indirect benefits of rotavirus vaccination would result in even greater declines in medical visits and additional cost-savings. Our analyses also may have underestimated the effectiveness of partial series vaccination as there is evidence from other countries that partial dose effectiveness of both vaccines may be higher than what was assumed [28–31]. However, given the high vaccine coverage, the low burden of disease in young age groups, and that most children complete the full series, the higher partial effectiveness has little impact on the overall cost effectiveness.
One final limitation of our study is that our estimate of $3 for rotavirus vaccine administration costs is lower than what has been used in previous cost-effectiveness analyses for countries with developed economies (range $3.50-$10.70) [32]. Although this was the best estimate we could obtain due to lack of available costing data, an underestimation of the true administration costs could result in an overestimation of the cost-effectiveness of rotavirus vaccination. However, the impact of this may be temporized by the likely underestimation of potential cost savings mentioned in the previous sections.
Previous studies have documented a substantial economic burden associated with treating rotavirus disease in young children in Taiwan and the potential benefits of a national rotavirus vaccination program [6, 17, 19]. Additional rotavirus vaccine cost-effectiveness studies have found that a national rotavirus vaccination program may be cost saving up to $27 per dose ($54 per course) and $20 to $25 per dose ($60 to $75 per course) for 2-dose and 3-dose rotavirus vaccination programs, respectively [18, 20]. While our study found lower breakeven prices of $13.30 per dose ($26.60 per course) and $7.98 per dose ($23.94 per course) for 2-dose and 3-dose vaccination programs, respectively, we did estimate prevention of a similar proportion of deaths, hospitalizations, and outpatient visits due to rotavirus as these other studies.
Several factors related to data sources and model inputs may have contributed to the lower break even prices and more conservative cost-effectiveness thresholds seen in our study. For example, the study of a 3-dose national vaccination program used diarrheal disease burden data from sentinel hospital surveillance sites from one area in Taiwan (and also included emergency department visits) and relied on 2010 cost data that were aggregated from rotavirus cases enrolled at these surveillance sites, which may not be generalizable to the country [18]. Another study of 2-dose and 3-dose vaccination programs used data from the NHIRD, but differed from our study in that 2006 data (vs. 2005 data) were used and a database sampling method was applied to obtain estimates of diarrheal disease burden rather than querying all relevant visits, which could have resulted in overestimates of disease burden [20]. Finally, both studies used a higher estimate for the proportion of diarrhea hospitalizations due to rotavirus rather than a mean of a range of estimates. A great strength of our study is the use of quality, nationally representative data for model inputs. With the exception of estimating the rotavirus-specific outpatient rate using a previously published method due to lack of rotavirus detection rate data in outpatient settings, we were able to obtain nationally representative healthcare utilization data directly from the NHIRD and DTP coverage data directly from the Taiwan Centers for Disease Control. In addition, we were able to use vaccine efficacy data from clinical trials conducted in Taiwan and two other similar Asian countries for one of the analyses [13].
Since financial barriers may play a large role in whether Taiwan will adopt rotavirus vaccines into the National Immunization Program, such data and post-marketing vaccine impact data should be used to inform policymakers about the potential costs and benefits of a national rotavirus vaccination program. Even though a vaccination program using the current market prices of $86 per dose of Rotarix and $67 per dose of RotaTeq would not be cost-effective, efforts could be made to acquire vaccine at prices that would be cost-effective and, in turn, would provide maximal public health benefits to the children of Taiwan.
CONCLUSIONS
Our findings suggest that a national rotavirus vaccination program using either of the currently licensed rotavirus vaccines may substantially reduce the burden of rotavirus disease among Taiwanese children and be a potentially cost-effective program if lower vaccines prices could be obtained. These data, in conjunction with other data regarding vaccine impact, cost-effectiveness, and finances and operations, should help inform policymakers in Taiwan when deciding whether to include rotavirus vaccines in the National Immunization Program.
Highlights.
Rotavirus vaccines are on the Taiwan private market, but not in the National Immunization Program.
We examined vaccination impact and cost-effectiveness from the health care system perspective.
A national rotavirus vaccination program could reduce greatly rotavirus disease burden.
A national rotavirus vaccination program could be cost-effective, depending on vaccine dose price.
ACKNOWLEDGEMENTS
We would like to thank Dr. Umesh Parashar (US CDC) for his advice and comments regarding the study design and manuscript; Ms. Hui-Tzu Yu and Ms. Han-Ying Lin (National Health Research Institutes, Taiwan) for assistance in collecting non-medical and indirect costs related to rotavirus hospitalization treatment; Ms. Ching-Yi Wu (National Health Research Institutes, Taiwan) for assistance in performing rotavirus RT-PCR testing; and Ms. Shiau-Mei Tsai (Changhua Christian Hospital, Taiwan), the Chang Gung Memorial Hospital Team (Taoyuan, Taiwan) and Wen-Ling Chuang (Kaohsiung Chang Gung Memorial Hospital, Taiwan) for their work at the sentinel surveillance sites.
FUNDING
This study was financially supported by the following research grant: “Technology Project for Surveillance and Prevalence of Gastroenteritis in Taiwan” from Centers for Disease Control, Department of Health, Execute Yuan, Taiwan (supported grant: DOH98-DC-1005).
Footnotes
Conflicts of interest: The authors have indicated that they have no conflicts of interest relevant to this article to disclose.
Disclaimer: The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention.
REFERENCES
- 1.Parashar UD, Burton A, Lanata C, et al. Global mortality associated with rotavirus disease among children in 2004. The Journal of infectious diseases 2009. Nov 1;200 Suppl 1:S9–S15. [DOI] [PubMed] [Google Scholar]
- 2.Parashar UD, Gibson CJ, Bresse JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerging infectious diseases 2006. Feb;12(2):304–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Tate JE, Burton AH, Boschi-Pinto C, et al. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. The Lancet infectious diseases 2012. Feb;12(2):136–41. [DOI] [PubMed] [Google Scholar]
- 4.Chen KT, Chen PY, Tang RB, et al. Sentinel hospital surveillance for rotavirus diarrhea in Taiwan, 2001–2003. The Journal of infectious diseases 2005. Sep 1;192 Suppl 1:S44–8. [DOI] [PubMed] [Google Scholar]
- 5.Chen SY, Chang YC, Lee YS, et al. Molecular epidemiology and clinical manifestations of viral gastroenteritis in hospitalized pediatric patients in Northern Taiwan. Journal of clinical microbiology 2007. Jun;45(6):2054–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lu CY, Lauderdale TL, Fang YH, et al. Disease burden and related medical costs of rotavirus infections in Taiwan. BMC infectious diseases 2006;6:176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wu FT, Liang SY, Tsao KC, et al. Hospital-based surveillance and molecular epidemiology of rotavirus infection in Taiwan, 2005–2007. Vaccine 2009. Nov 20;27 Suppl 5:F50–4. [DOI] [PubMed] [Google Scholar]
- 8.Rotavirus vaccines:an update. Releve epidemiologique hebdomadaire / Section d’hygiene du Secretariat de la Societe des Nations = Weekly epidemiological record / Health Section of the Secretariat of the League of Nations 2009. Dec 18;84(50):533–40. [PubMed] [Google Scholar]
- 9.Esposito DH, Tate JE, Kang G, Parashar UD. Projected impact and cost-effectiveness of a rotavirus vaccination program in India, 2008. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2011. Jan 15;52(2):171–7. [DOI] [PubMed] [Google Scholar]
- 10.Rheingans RD, Antil L, Dreibelbis R, Podewils LJ, Bresee JS, Parashar UD. Economic costs of rotavirus gastroenteritis and cost-effectiveness of vaccination in developing countries. The Journal of infectious diseases 2009. Nov 1;200 Suppl 1:S16–27. [DOI] [PubMed] [Google Scholar]
- 11.Tate JE, Rheingans RD, O’Reilly CE, et al. Rotavirus disease burden and impact and cost-effectiveness of a rotavirus vaccination program in kenya. The Journal of infectious diseases 2009. Nov 1;200 Suppl 1:S76–84. [DOI] [PubMed] [Google Scholar]
- 12.Organization WH. Generalized cost-effectiveness analysis: a guide. Geneva: World Health Organization, 2002. [Google Scholar]
- 13.Phua KB, Lim FS, Lau YL, et al. Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study. Vaccine 2009. Oct 9;27(43):5936–41. [DOI] [PubMed] [Google Scholar]
- 14.Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. The New England journal of medicine 2006. Jan 5;354(1):23–33. [DOI] [PubMed] [Google Scholar]
- 15.Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. The Journal of infectious diseases 1996. Sep;174 Suppl 1:S5–11. [DOI] [PubMed] [Google Scholar]
- 16.Parashar UD, Holman RC, Clarke MJ, Bresee JS, Glass RI. Hospitalizations associated with rotavirus diarrhea in the United States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus-specific diagnostic code. The Journal of infectious diseases 1998. Jan;177(1):13–7. [DOI] [PubMed] [Google Scholar]
- 17.Chen KT, Fan SF, Tang RB, et al. Hospital-based study of the economic burden associated with rotavirus diarrhea in Taiwan. Vaccine 2007. May 22;25(21):4266–72. [DOI] [PubMed] [Google Scholar]
- 18.Itzler RF, Chen PY, Lac C, El Khoury AC, Cook JR. Cost-effectiveness of a pentavalent human-bovine reassortant rotavirus vaccine for children </=5 years of age in Taiwan. Journal of medical economics 2011;14(6):748–58. [DOI] [PubMed] [Google Scholar]
- 19.Mast TC, Chen PY, Lu KC, et al. Epidemiology and economic burden of rotavirus gastroenteritis in hospitals and paediatric clinics in Taiwan, 2005–2006. Vaccine 2010. Apr 9;28(17):3008–13. [DOI] [PubMed] [Google Scholar]
- 20.Wu CL, Yang YC, Huang LM, Chen KT. Cost-effectiveness of childhood rotavirus vaccination in Taiwan. Vaccine 2009. Mar 4;27(10):1492–9. [DOI] [PubMed] [Google Scholar]
- 21.Cortese MM, Tate JE, Simonsen L, Edelman L, Parashar UD. Reduction in gastroenteritis in United States children and correlation with early rotavirus vaccine uptake from national medical claims databases. The Pediatric infectious disease journal 2010. Jun;29(6):489–94. [DOI] [PubMed] [Google Scholar]
- 22.Curns AT, Steiner CA, Barrett M, Hunter K, Wilson E, Parashar UD. Reduction in Acute Gastroenteritis Hospitalizations in US Children After Introduction of Rotavirus Vaccine - Analysis of Hospital Discharge Data from 18 States. The Journal of infectious diseases 2010;In press. [DOI] [PubMed] [Google Scholar]
- 23.Field EJ, Vally H, Grimwood K, Lambert SB. Pentavalent rotavirus vaccine and prevention of gastroenteritis hospitalizations in Australia. Pediatrics 2010. Sep;126(3):e506–12. [DOI] [PubMed] [Google Scholar]
- 24.Lopman BA, Curns AT, Yen C, Parashar UD. Infant rotavirus vaccination may provide indirect protection to older children and adults in the United States. The Journal of infectious diseases 2011. Oct 1;204(7):980–6. [DOI] [PubMed] [Google Scholar]
- 25.Paulke-Korinek M, Kundi M, Rendi-Wagner P, et al. Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria. Vaccine 2011. Mar 24;29(15):2791–6. [DOI] [PubMed] [Google Scholar]
- 26.Yen C, Armero Guardado JA, Alberto P, et al. Decline in Rotavirus Hospitalizations and Health Care Visits for Childhood Diarrhea Following Rotavirus Vaccination in El Salvador. The Pediatric infectious disease journal Nov 2. [DOI] [PubMed] [Google Scholar]
- 27.Yen C, Tate JE, Wenk JD, Harris JM, Parashar u. Diarrhea-associated hospitalizations among US children over 2 rotavirus seasons after vaccine introduction. Pediatrics 2011;127(1):In press. [DOI] [PubMed] [Google Scholar]
- 28.Braeckman T, Van Herck K, Meyer N, et al. Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study. Bmj 2012;345:e4752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Cortese MM, Leblanc J, White KE, et al. Leveraging state immunization information systems to measure the effectiveness of rotavirus vaccine. Pediatrics 2011. Dec;128(6):e1474–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Martinon-Torres F, Bouzon Alejandro M, Redondo Collazo L, et al. Effectiveness of rotavirus vaccination in Spain. Human vaccines 2011. Jul;7(7):757–61. [DOI] [PubMed] [Google Scholar]
- 31.Staat MA, Payne DC, Donauer S, et al. Effectiveness of pentavalent rotavirus vaccine against severe disease. Pediatrics 2011. Aug;128(2):e267–75. [DOI] [PubMed] [Google Scholar]
- 32.De la Hoz-Restrepo F, Castañeda-Orjuela C, Paternina A, Alvis-Guzman N. Systematic review of incremental non-vaccine cost estimates used in cost-effectiveness analysis on the introduction of rotavirus and pneumococcal vaccines. [DOI] [PubMed]