Committee Report number: 2012022
Paper for Meeting on: 24 April 2012
NHC reference: Action Point from NHC meeting on 26 March 2012
The National Health Committee
Recommendation - Rotavirus Vaccination
Executive summary
i.
At the previous Committee meeting (26 March 2012) a draft of the Rotavirus assessment
report was provided to the Committee as part of the ‘stage gate’ process of determining what
further evidence the Committee requires prior to making a decision.
ii.
The Committee instructed the Executive to further investigate the impact of targeting
vaccination to patients at high risk of nosocomial rotavirus gastroenteritis on the clinical- and
cost-effectiveness of the programme. A limited ‘light’ literature search was suggested and the
findings of this search are presented in Appendix 1.
iii.
This recommendations paper summarises the key points from the draft rotavirus assessment
report presented at the last Committee meeting (see paper # 2012014) and the additional
evidence retrieved (refer para 2); detailing why the intervention was chosen for assessment,
the methods used in the assessment, and a brief discussion of the results and limitations.
iv.
The paper uses this evidence to evaluate the performance of the intervention against the
Committee’s 11 decision-making criteria, and makes a recommendation consistent with this.
v.
Finally, the circumstances under which a review of the recommendation would be triggered in
the future are described.
It is recommended that you:
a)
Agree that the Committee has sufficient information to make a decision.
Yes / No
b)
Agree to recommend to the Minister of Health that the Ministry of Health should
not fund the universal vaccination of children for rotavirus gastroenteritis.
Yes / No
b)
Consider that if an alternative recommendation is preferred, further work by the
Executive is required to determine the most acceptable and clinically- and cost
Yes / No
–effective method of implementation (as per assessment report tabled at 26
March meeting, refers to paper #2012014).
Committee Report number: 2012022
Preamble
1. Relative to other OECD countries, New Zealand has unusually high rates of infectious
diseases such as campylobacteriosis, acute rheumatic fever, childhood pneumonia,
meningococcal disease, and skin infections1.
2. A recent New Zealand study has also shown that infectious diseases make the largest
contribution to acute hospital admissions and that over the last 20 years rates have increased
more than for any other major cause2. The age-standardised rate of acute admissions for
infectious disease has also risen much more than the rate for non-infectious disease
admissions and the risk of admission is significantly higher in the most economically deprived
populations, in Maori and Pacific peoples, and in the youngest (under 5 years) and oldest age
groups (over 70 years).
3. The study found that infectious disease categories with the most acute hospital admissions
were lower respiratory tract infections, skin and soft-tissue infections, and enteric infections
(associated with the intestine). Bacterial, rather than viral are the main drivers of infections.
4. These findings support the experience and current strategies of many District Health Boards;
many of which are currently prioritising child health and in particular the prevention and
treatment of these infectious diseases.
Policy Question
5. The purpose of this paper is to recommend whether, on the basis of the NHC’s assessment
of the evidence, and awareness of competing priorities in infectious disease control and child
health, the Ministry of Health should fund the universal vaccination of infants against rotavirus
gastroenteritis.
6. It follows a recommendation by the Immunisation Technical Forum (ITF) that a two dose
rotavirus vaccine be added to the immunisation schedule. No preference for either the Merck
Sharp & Dohme (MSD) or GlaxoSmithKline (GSK) vaccines was expressed by the ITF.
Rationale for assessment
7. The estimated annual incidence of rotavirus is 1,500 per 100,000 of the population, the
incidence of hospitalisation for rotavirus is 22.5 per 100,000 of the population, and the annual
rotavirus mortality rate is approximately 0.01 per 100,000.
8. Rotavirus vaccination is recommended by the World Health Organization (WHO). The United
States, Australia, and parts of Europe (including Austria, Belgium & Finland)(World Health
Organization, 2011), have all adopted recommendations to routinely immunize children for
rotavirus. However in England it is currently felt that the public health risks posed by rotavirus
do not warrant routine vaccination3 and in Canada decisions around public funding are
awaiting the results of cost-effectiveness analyses4.
9. In New Zealand, rotavirus vaccination is recommended, but not currently funded for all infants
(the first dose must be received by age 15 weeks) and especially infants who will be regularly
attending early childhood services or where there is an immune-compromised individual living
in the household.
1
Baker, M. G., Barnard, L. T., Kvalsvig, A., Verrall, A., Zhang, J., Keall, M., et al. (2012). Increasing
incidence of serious infectious diseases and inequalities in New Zealand: a national epidemiological study.
The Lancet(DOI:10.1016/S0140-6736(11)61780-7).
2 Baker, M. G., Barnard, L. T., Kvalsvig, A., Verrall, A., Zhang, J., Keall, M., et al. (2012). Increasing
incidence of serious infectious diseases and inequalities in New Zealand: a national epidemiological study.
The Lancet(DOI:10.1016/S0140-6736(11)61780-7).
3 http://www.nhs.uk/Conditions/Rotavirus-gastroenteritis/Pages/Prevention.aspx
4 http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/10vol36/acs-4/index-eng.php
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Committee Report number: 2012022
10. In 2009, the Immunisation Technical Forum (ITF) recommended that a two dose rotavirus
vaccination programme be publicly funded for infants.
11. The ITF, appointed by the Director-General of Health, reviews the Schedule every three
years and makes recommendations on the use of current vaccines and new vaccines (or new
combinations of vaccines) to be added to the Schedule.
12. The ITF bases its advice on technical evidence on the clinical effectiveness of new vaccines,
epidemiology, availability of new types of vaccines and sector capability. Historically, a full
HTA of a vaccine has not been undertaken, and the other domains (such as value for money,
societal & ethical, and feasibility of adoption in the system) have only been considered on an
ad-hoc basis.
13. A full assessment of the addition of rotavirus to the vaccine schedule was needed to support
advice to the Minister on a budget bid in September 2012 on whether or not to add the
rotavirus vaccine to the Schedule at its next revision in 2014.
14. The rationale for the involvement of the NHC stems from the:
 Immunisation team needing to show it is taking account of value for money in vaccines
prioritisation
 NHC wanting to signal their intent to work in the area of vaccines in the future
Technology Status & commercial considerations in New Zealand
15. Both Rotarix® (manufactured by GlaxoSmithKlein) and RotaTeq® (manufactured by Merck
Sharp & Dohme Corp) vaccines are currently available in New Zealand (Table 1). The
Rotarix vaccine is given in two oral doses at the same time as the routine Schedule, while the
RotaTeq vaccine is administered as a three-dose oral course at the same time as the routine
Schedule.
16. No preference for either the Merck Sharp & Dohme (MSD) or GlaxoSmithKline (GSK)
vaccines was expressed by the ITF.
Table 1: Brands of Rotavirus vaccine approved for distribution in New Zealand
Brand
Registration situation
Advertised unit price
($NZ)
Rotarix Oral Vaccine Oral
Consent given, and approved:
$107 to $180 ($80
suspension, 1000000CCID50
26/03/2009
wholesale)
(Prescription)
Rotarix Powder with diluent for oral Not marketed, but
Currently unavailable for
suspension, 1000000CCID50
approved:11/04/2008
private purchase
(Prescription)
RotaTeq Oral suspension, 2mL
Consent given, and approved:
Currently unavailable for
(Prescription)
22/03/2007
private purchase
Source: Medsafe (http://www.medsafe.govt.nz/regulatory/ <date accessed: 28/02/12>)
17. The required annual volume of vaccine for a three dose schedule, assuming 100% uptake
would be approximately 180,000 units (an entire birth cohort). However, uptake is likely to
start lower and increase over time from around 30% (54,000 units) to hopefully reaching
about 85% (153,000 units) after five years. A two dose schedule would require slightly less
than the volumes detailed above; with 30% uptake requiring 36,000 and 85% requiring
102,000 doses).
18. Overall the introduction of the rotavirus vaccine to the schedule would mean a long term
commitment to publically funded provision of the vaccine. This commitment has important
commercial implications as it indicates to suppliers that they will have an on-going captive
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Committee Report number: 2012022
market for their vaccine. Furthermore, unlike the varicella vaccine where different brands of
the vaccine can be used for different doses in the same individual, the available rotavirus
vaccines are not interchangeable, making it more difficult to switch between competing
suppliers.
19. While most patents expire after 20 years, enabling the entry of generics into the market after
this time, vaccine manufacturers are able to develop their vaccines in a way that enables
slight changes in the formulation to be re-patented; extending the time the company has a
monopoly in the market by preventing the entry of competitors.
20. These issues mean that negotiating good prices for vaccines is incredibly difficult, particularly
after a decision has already been made to add the vaccine to the schedule.
Methods
21. Health Technology Assessment is a multidisciplinary field of policy analysis that studies the
medical, economic, social and ethical implications of development, diffusion and use of health
technology. It usually involves systematic reviews of the literature, epidemiological and
financial analysis of administrative health data, economic evaluation and budget impact
analysis, and public and health sector engagement. It aims to answer a specific set of
research questions across domains in order to answer an overall policy question around
investment. The method used in the assessment of the addition of rotavirus vaccine to the
immunisation schedule is described below.
22. On the 26 September 2011 the Ministry of Health reference librarians systematically
searched the sites of key Health Technology Assessment (HTA) agencies and repositories
using the following search terms: Rotavirus. Following this initial search of HTA agencies
and repositories, Ovid MEDLINE® and Cochrane Library were searched for scientific journal
papers published between 1 January 2009 and 28 October 2011. The search terms used
were: cost-effectiveness, cost-benefit, cost-utility, economic evaluation, economic model,
decision analysis, rotavirus vaccination. Results were limited to either systematic reviews OR
studies based in the United States, Europe, Canada, Australia, or New Zealand. No
language limits were applied. A subsequent search of EMBASE for papers published
between 1 January 2009 and 11 November 2011, using the same inclusion and exclusion
criteria was also undertaken. The reference lists of identified publications were not searched.
23. Abstracts were sifted through and categorised, on the basis of their content, into one of four
domains: Economic, Clinical, Social & Ethical, and Feasibility of Adoption within the system.
All abstracts were included (regardless of position on evidence hierarchy) but only the full text
of relevant studies where further detail was required was retrieved. No formal critical
appraisal of studies was undertaken. Abstracts and full papers retrieved were used to create
a narrative summary of the issues relevant to each domain and answer the specific research
questions. If, after producing the narrative summaries for each domain the key research
questions had not been addressed, further targeted searches using Google and Google
scholar were undertaken. This strategy was used primarily to identify context-specific
information required to answer questions in the ‘societal and ethical’ and ‘feasibility of
adoption within the system’ domains and included New Zealand-specific information on
immunisation coverage, as well as an investigation of other vaccines on the horizon.
24. The results of an economic evaluation provided to the Ministry of Health’s immunisation team
on 20 January 2012 were critically appraised and used to provide contextualised answers to
the cost-effectiveness questions posed in the economic domain.
Summary of findings
Clinical Domain (includes safety & effectiveness of vaccine and workforce considerations)
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Committee Report number: 2012022
25. Overall, current evidence suggests that both rotavirus vaccines available in New Zealand
(Rotarix & RotaTeq) are safe and effective for use in most infants, alongside existing
immunisations on the schedule. While there were initial concerns around the clinical safety of
early rotavirus vaccines related to the heightened risk of intussusception (Rotashield), large
phase III pre-licensure clinical trials of Rotarix and RotaTeq vaccines have not detected an
increased risk (though post marketing surveillance indicates the possibility of a slightly
increased risk shortly after the first dose in some populations).
26. Vaccines are prescription medicines, so they can only be administrated by medical
practitioners, registered midwives, designated prescribers (including registered nurses), and
people authorised to administer the medicine in accordance with a standing order. Given that
it is proposed for the rotavirus vaccine to be given alongside existing vaccines on the
schedule, no significant workforce implications are envisaged from a delivery perspective.
However, there may be workforce implications from implementing the surveillance program
that needs to accompany the roll-out of the vaccine.
Economic Domain (value for money – ie, cost-effectiveness)
27. A three or two dose universal rotavirus vaccination program will increase health sector costs
rather than decrease them (ie, the program will not result in cost-savings). The costeffectiveness of the program to the health payer is influenced by the price of the vaccine, and
number of doses.
28. The annual medical costs incurred from rotavirus are estimated to be around $3.0 million, and
if the assumptions of the economic model are correct, spending $7.9 million on a three-dose
universal rotavirus vaccination programme for infants could save $2.3 million in medical costs
(75% of total medical costs for rotavirus).
29. It is also anticipated that the annual number of rotavirus cases will decrease by 68% (from
60,000 to 19,050), and the number of cases requiring general practice and hospital care is
expected to decrease by 78% (from 7,020 to 1,526) and 87% (from 900 to 114), respectively.
Each year, a universal rotavirus vaccination programme could also result in the gain of 116
quality adjusted life years (QALYs).
30. In the New Zealand model, a three dose universal rotavirus vaccination programme was
estimated to cost $62,000 per QALY gained.
31. In this scenario, universal rotavirus vaccination only became cost-saving to the health payer
when the price of each dose of the vaccine decreased by more than half (from $50 to $15).
32. No studies were retrieved during the systematic search which explored the cost-effectiveness
of reducing the number of doses, and the New Zealand evaluation did not investigate this.
However, all cost-utility analyses retrieved comparing the cost effectiveness of two dose
(Rotarix) versus three dose (RotaTeq) brands found that the 2 dose brand was more costeffective than the three dose brand.
33. The cost-effectiveness of the program to the health sector may also be improved if the costs
of nosocomial5 infection were included in the analysis. However, results are still unlikely to be
cost-saving to the health payer.
34. Some work has occurred in Canada suggesting that an immunisation strategy that targets
patients at high risk of nosocomial rotavirus (such as infants with congenital pathology and
low birth weight) may be more cost-effective than universal vaccination. The authors
suggested that countries yet to introduce universal vaccination should assess targeted
5
A nosocomial infection is one acquired in hospital. No data on the incidence of nosocomial rotavirus infection in New Zealand was
readily available, but if rates are similar to Canada, the incidence may be around 0.30 per 100 hospital admissions (see Verhagen P,
Moore D, Manges A, Quach C. Nosocomial rotavirus gastroenteritis in a Canadian paediatric hospital: Incidence, disease burden and
patients affected. Journal of Hospital Infection 2011;79 (1):59-63)
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Committee Report number: 2012022
vaccination. However, the authors stopped this work after most Canadian provinces and
territories implemented a universal vaccination strategy. No other studies looking at targeted
rotavirus vaccination could be identified (Appendix 1).
35. While rotavirus vaccination appears to be the preferred prevention method for nosocomial
rotavirus infection, there are other effective prevention methods and the relative costeffectiveness of a vaccination strategy should be compared with these, particularly given their
potential to reduce other hospital infections. For instance, breastfeeding (symptoms are less
severe in breast fed infants), passive immunisation with antibodies, changes to hospital
infection control interventions, and the use of probiotics, including administration of
Lactobacillus GG (LGG) (Appendix 1).
36. If rotavirus vaccination was going to be used specifically to address nosocomial infections,
the cost-effectiveness of this prevention method should be compared with other prevention
methods first which would be the subject of a separate assessment.
Societal & Ethical Domain (including acceptability and equity)
37. There is insufficient qualitative research to determine how New Zealand health practitioners
and the public would prioritise a universal rotavirus vaccination programme in New Zealand.
Further sociological research into public perceptions and prioritisation of vaccines, and new
interventions generally in New Zealand, is necessary for this domain do be addressed
adequately.
38. However, evidence from overseas and the coverage rates for existing vaccines on the New
Zealand schedule suggest that rotavirus vaccination may not be perceived as a high priority
for public funding-– particularly in the context of disparities in coverage for existing publiclyfunded immunisations and the high incidence of other infectious diseases.
39. Internationally, rotavirus vaccination is prioritised lower than other vaccines by health
practitioners (including the chickenpox vaccine) and continues to have lower uptake than
vaccines currently on the schedule.
40. It has also been suggested that the addition of yet another vaccine in this age-group may not
be acceptable to the public. However, as it is delivered orally, it may be more feasible and
acceptable to parents than vaccines that require an injection (eg, varicella).
41. Similar issues and examples discussed in the varicella recommendations paper are also
relevant here (NHC paper # 2012021 refers).
Financial Domain (includes feasibility of adoption and budget impact)
42. There are significant costs in implementing a vaccination program, not all of which were
captured in the economic model, and many of which are difficult to estimate – hindering a
determination of whether the vaccine is affordable and feasible to adopt.
43. In addition to the annual cost of the vaccine and administration/delivery costs (considered in
the economic model), there are also costs associated with education and promotion, and
compliance and surveillance, as well as additional one-off set-up costs associated with the
supply chain (which were not considered in the economic model). Estimates of some of
these costs are provided in Table 2.
Table 2: Estimated annual costs of delivering a universal rotavirus vaccination programme with
100% uptake.
Item
Rotavirus vaccine (wholesale – excl
GST & freight)
National Health Committee April 2012
Cost
Cost per Cost per
Source
per
person
cohort
dose
$50.00 $150.00 $9,000,000.00 Manufacturers
(2012)
Page 6 of 16
Committee Report number: 2012022
Administration/delivery costs
(2007/08)
$25.67
Surveillance and service audit, and
research and evaluation6
n/a
Promotion & advertising7
n/a
Total
$75.67
$77.01 $4,620,600.00 Immunisation
Advisory
Centre1
n/a
$500,000.00 Health Report
number:
20110143
n/a
$100,000.00 Health Report
number:
20110143
$227.01
$14,220,600
Note: Items highlighted grey are confidential and not for public dissemination.
44. Prior to implementation a comprehensive surveillance system will need to be established to
monitor waning immunity, changing dominance of specific rotavirus strains and the risk of
intussusception. The costs to, and burden on, the health sector of setting up a new system,
or making rotavirus a notifiable diseases under the existing system have not been included in
the current evaluation of cost-effectiveness. Once these costs are included, the costeffectiveness of universal vaccination is likely to further decrease from the perspective of the
health payer, and place additional pressure on District Health Boards (DHBs) and labs.
45. DHBs also experience costs associated with ensuring adequate uptake through the use of
out-reach services, which are estimated to cost between $250 and $1000 per hard to reach
child. As the rotavirus vaccine would be delivered at the same time as existing vaccines, outreach costs would not increase. However, the failure to factor these costs into initial
decisions about the addition of existing vaccines on the immunisation schedule may mean
DHBs are currently resourcing activities they are not being adequately reimbursed for.
46. Currently, information on the costs associated with the supply chain for vaccines (including
rotavirus) are unknown and often these costs are identified after a decision to add a vaccine
to the schedule has been made. In the future all the costs associated with delivering a new
vaccine program need to be identified prior to undertaking an economic evaluation of its costeffectiveness so that its funding can be prioritised accurately.
47. The exclusion of these costs from the economic evaluation and prioritisation of vaccines is
not a shortcoming unique to New Zealand – these costs are often not identified in
assessments overseas. However, in order to adequately assess whether different parts of
the system have sufficient slack to absorb the addition of subsequent vaccines, a framework
that accounts for these costs and adjusts accordingly, is required.
48. Furthermore, it will be important for future economic evaluations of vaccines in New Zealand
to use a standard model that adequately reflects the impact of herd immunity and
transmission dynamics of infectious diseases which can influence the cost-effectiveness of
vaccines.
49. The whole process of assessing, prioritising and procuring new vaccines in New Zealand is
currently the subject of a policy paper being developed in the Policy Business Unit of the
Ministry of Health so the actual procurement process at this stage is uncertain.
6
7
This is based on an estimate for the rheumatic fever programme. More accurate data should be
located.
This is based on an estimate for the rheumatic fever programme. More accurate data should be
located.
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Committee Report number: 2012022
Social economic benefit
50. The cost-effectiveness of a universal rotavirus vaccination program is greater from a societal
perspective than a health payers perspective but is still not cost saving. From a societal
perspective, the programme would return $0.97 in productivity savings for every dollar spent.
51. Each year, rotavirus costs the New Zealand economy approximately $8.3 million through lost
productivity as a result of parental time spent caring for sick children instead of working, and
loss of future earnings through death.
52. If the assumptions of the model are correct, spending $7.9 million on a universal rotavirus
vaccination programme for infants could save $6 million in lost productivity (72% of total
productivity costs).
Limitations and uncertainty
53. The conclusions drawn in the societal and ethical domain were not informed through
engaging directly with New Zealand health practitioners and public but were based on
coverage rates for existing vaccines and evidence from overseas.
54. The economic evaluation was not informed by a systematic review and critical appraisal of
the evidence on clinical safety and effectiveness, but was based on the expertise of the
Immunisation Technical Forum (ITF).
55. The economic evaluation did not include all costs associated with implementation – including
surveillance and promotion/education and the coverage parameters for vaccination may have
been optimistic. It is also unclear how sensitive the results are to a reduction in the number
of doses (from three to two).
56. It is unclear how ‘real’ the societal savings are, and if they do exist, whether it is appropriate
for Vote: Health to fund the costs of the program when the majority of the benefits accrue
elsewhere.
57. The actual price of the vaccine is unknown until a decision is made to adopt the universal
vaccination program and negotiations commence.
Prioritisation
58. An additional consideration is whether a universal rotavirus vaccination programme would be
the best use of public money when compared with other potential spending in the space of
vaccines, infectious diseases and child health more broadly which may generate greater
health gains and result in cost-savings to the health system.
59. A three dose rotavirus vaccination programme is less cost-effective (ie, it would return lower
health gains for the money spent) than a two dose varicella vaccination programme. While
the crude incidence and mortality rate for rotavirus is less than varicella, the hospitalisation
rate is nearly five times higher.
60. Rather than funding the addition of either vaccine to the schedule the money may be better
spent on increasing coverage rates for existing vaccines on the schedule (including among
‘hard to reach’ population groups), saved to fund other, potentially more beneficial vaccines
on the horizon, or spent in other areas of child health which are likely to produce greater
health gains.
Performance against criteria
61. Overall, the public funding of universal rotavirus vaccination of children does not perform well
when evaluated against the Committee’s decision-making criteria. Of the eleven criteria, the
intervention only met ‘well’ or ‘very well’ the criteria for clinical safety and effectiveness and
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Committee Report number: 2012022
‘risk’. It ‘somewhat’ met the criteria of health and independence gain, but did not meet very
well the criteria of materiality, feasibility, policy congruence, equity, acceptability, costeffectiveness or affordability (Figure 1).
Figure 1: Evaluation of universal rotavirus vaccination against decision-making criteria with
respect to the Vote: Health budget
How well does the proposal fit the NHC's criteria?
Criteria
Not at all
Not very well Somewhat
Well
Very Well
Clinical Safety and Effectiveness
Health and Independence Gain
Materiality
Feasibility
Policy Congruence
Equity
Acceptability
Cost Effectiveness (Value for Money)
Affordability
Risk
Other Criteria as the NHC thinks fit.
Explanation
The available vaccines are clinically safe &
effective in most cases.
There is a health gain, but rotavirus is usually a
relatively mild disease so the health gain is
low er than for other interventions.
There are productivity gains, but the gains to
the health system are small.
Increased surveillance burden on health sector
and potential difficulties in achieving required
coverage.
Potential to distract from a focus on increasing
immunisation coverage.
Disease experienced similarly by different subgroups of the population but uptake of
intervention, and thus benefits likely to be
unequally distributed.
Rotavirus is view ed as moderately severe and
oral delivery (rather than injection) may appeal,
but another vaccination in childhood may not
be acceptable to the public particularly given
overseas experience w ith Rotashield.
Estimated to cost the health payer $62k/QALY
gained and result in societal savings (from
reducing parental time off w ork) of approx $6
million.
Given other competing priorities this vaccine
may not be affordable in the long-term.
The risk of introducing the intervention is not
more significant than the risk of not introducing
the intervention.
N/A
Recommendation
As the intervention does not perform well or very well against over half of the Committee’s
criteria, it is suggested that they recommend that the Ministry of Health does not fund the
universal vaccination of infants for rotavirus gastroenteritis. The net avoided costs from this
recommendation would be $5.6 million per annum8, but the opportunity for a gain of 116 QALYs
and savings of $6 million in lost productivity would be foregone. Note that the estimated net
avoided costs are based on the economic evaluation which did not consider all the costs of the
programme. This means that the net avoided costs are a conservative estimate and that the
actual costs avoided are much higher.
Criteria for review
Every recommendation made by the NHC is subject to review if the evidence upon which the
assessment and recommendations are based changes. The recommendation not to publicly
fund a universal rotavirus vaccination programme for infants will be reviewed if the:
8

price of the vaccines reduce to less than $15.00 per dose or

the severity of disease experience significantly increases or

health care costs associated with rotavirus significantly increase or
= Cost of vaccine ($7.9 million) – Cost of medical costs saved through vaccination ($2.3 million)
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
public demand for the vaccine increases and

coverage for existing vaccines on the schedule reaches recommended levels (ie, there is
evidence that the vaccine is acceptable and a high priority to the public and the risk of a
new vaccine affecting coverage for existing vaccines declines).

END.
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Appendix 1: Summary of additional evidence requested
1. At the previous Committee meeting (26 March 2012) a draft of the Rotavirus assessment
report was provided to the Committee as part of the ‘stage gate’ process of determining what
further evidence the Committee requires prior to making a decision.
2. The Committee instructed the Executive to further investigate the impact of targeting
vaccination to patients at high risk of nosocomial rotavirus gastroenteritis on the clinical- and
cost-effectiveness of the programme. A limited ‘light’ literature search was suggested and the
methods used for, and findings of this search are presented below.
3. On the 30 March 2012 the Ministry of Health reference librarians systematically searched
Ovid MEDLINE® and Cochrane Library for all scientific journal papers published using the
following search terms (and variations thereof): Rotavirus, vaccine, targeting, nosocomial
infection, systematic review, health technology assessment, cost-effectiveness, vulnerable
children. The full search strategy is provided in Appendix 2.
4. As this search only identified 20 papers, of which the only relevant one was the Canadian
study that was identified previously during the main search, the authors of the Canadian
study were approached to determine what further work they had undertaken and whether
they were aware of any other studies. They had not completed any further work and were
unaware of other studies (email correspondence supplied in Appendix 2).
5. On the 2 April 2012 the Ministry of Health reference librarians systematically searched Ovid
MEDLINE® and Cochrane Library for all commercial journal papers published using similar
search terms as above but widening the search to include the most clinically and costeffective method for the prevention of nosocomial infections in hospitals.
6. While none of the 77 studies identified were comparative studies that definitively stated which
was the most clinically or cost-effective method, abstracts of some of these papers suggest
that there are a number of clinically effective alternatives for the prevention of nosocomial
infections that may be more cost-effective than universal rotavirus vaccination.
7. Alternatives to rotavirus vaccination for the prevention of nosocomial rotavirus infection
include:
a. Changes to hospital infection control interventions, including hand washing, gloves,
isolation etc2-5
a. Breast milk and promotion of breast feeding (symptoms are less severe in breast fed
infants) 5-8
b. Passive immunisation with antibodies including bovine colostrum and gammaglobulin5,9,10
c. The use of probiotics, including administration of Lactobacillus GG (LGG)5,11-14
d. Increased awareness of undiagnosed transmissible diseases15,16
8. Mrukowicz et al5 (2008) summarised the evidence on the non-vaccine options available for
the prevention of Rotavirus infection. They concluded that improvements in sanitation and
hand-washing were shown to have limited benefit and that while passive immunisation had
been used successfully for rotavirus gastroenteritis (RVGE) prevention in hospitals, no
commercial preparations were available. They also concluded that while probiotics had
shown promise, cost-effectiveness analyses were still required, and that while breast feeding
is recommended, it appears to postpone rather than prevent RVGE.
Next steps
9. To determine which method is most cost-effective would require another/separate economic
evaluation and additional HTAs in order to assess these interventions against the
Committee’s other domains and decision-making criteria (including clinical effectiveness and
feasibility of adoption).
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10. Prior to doing this it would also be necessary to determine whether the epidemiological and
financial burden of nosocomial rotavirus infection in New Zealand was significant enough to
dedicate assessment resources to – this may require primary data analysis due to the
absence of this data in the literature.
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Committee Report number: 2012022
Appendix 2: Search strategies, email correspondence and references relating to
additional evidence.
SEARCH STRATEGIES
1. Search Run on 30-March-2012
Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
<1946 to Present>
Search Strategy:
-------------------------------------------------------------------------------1 rotavirus OR rotarix OR rotateq.mp OR ("rix4414" or rix4414).mp OR "wc-3".mp
2 exp rotavirus/
3 exp rotavirus infections/
4 exp rotavirus vaccines/
5 1 or 2 or 3 or 4
6 exp vaccines/
7 vaccin*.mp.
8 5 and (6 or 7)
9 target*.mp.
10 Vulnerable Populations/
11 (vulnerabl* adj3 (child* or infant* or toddler or baby or babies)).mp. [mp=title, abstract,
original title, name of substance word, subject heading word, protocol supplementary concept,
rare disease supplementary concept, unique identifier]
12 8 and (9 or 10 or 11)
13 5 and target*.mp. and universal*.mp. [mp=title, abstract, original title, name of substance
word, subject heading word, protocol supplementary concept, rare disease supplementary
concept, unique identifier]
14 12 or 13
15 economic evaluation*.mp.
16 Cost-Benefit Analysis/
17 cost effectiveness analys*.mp.
18 cost utility.mp.
19 Models, Economic/
20 decision analys*.mp.
21 "Costs and Cost Analysis"/
22 systematic review*.mp.
23 health technol*.mp.
24 Technology Assessment, Biomedical/ or assessment.mp
25 Risk Factors/ or Risk/ or Risk Assessment/
26 14 and (15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25)
***************************
Cochrane Library
Current Search History
ID Search Hits Edit Delete
#1 MeSH descriptor Rotavirus explode all trees
#2 MeSH descriptor Rotavirus Infections explode all trees
#3 MeSH descriptor Rotavirus Vaccines explode all trees
#4 (rotavirus):ti,ab,kw 429
National Health Committee April 2012
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Committee Report number: 2012022
#5 (target*):ti,ab,kw or (vulnerable):ti,ab,kw
#6 (#1 OR #2 OR #3 OR #4) 429
#7 (#5 AND #6) 2
2. Search Run on 2 April 2011
Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)
<1946 to Present>
Search Strategy:
-------------------------------------------------------------------------------1 exp Gastroenteritis/pc (4723)
2 Rotavirus Infections/pc [Prevention & Control] (1262)
3 child/ or child, preschool/ or infant/ (1587987)
4 Cross Infection/ (41380)
5 (nosocomial adj2 infection*).ab,ti. (9599)
6 (hospital adj2 acquired).ab,ti. (4473)
7 (1 or 2) and 3 and (4 or 5 or 6) (72)
***************************
Cochrane Library
#1 MeSH descriptor Gastroenteritis explode all trees with qualifier: PC 406
#2 MeSH descriptor Rotavirus Infections explode all trees with qualifier: PC 178
#3 (#1 OR #2) 522
#4 MeSH descriptor Cross Infection explode all trees 1104
#5 (nosocomial infection*):ti,ab,kw or (hospital acquired):ti,ab,kw 972
#6 (#4 OR #5) 1783
#7 (#3 AND #6) 26
#8 (child*):ti,ab,kw or (infant*):ti,ab,kw or (newborn*):ti,ab,kw or (toddler*):ti,ab,kw or
(bab*):ti,ab,kw 78159
#9 (#7 AND #8) 16
EMAIL CORRESPONDENCE
I haven't come across anyone else looking at targeted RV immunization.
The only country that may be looking at different strategies is The Netherlands. My graduate student at the
time, Patricia Verhagen (now Bruijning) is now back at Utrecht University and is continuing the work... that
we are not able to do anymore in Canada, as most provinces and territories have now implemented
universal RV vaccination using RV1.
In the Province of Quebec, where we tend to look at different strategies, we were actually planning a RCT
to determine the vaccine effectiveness of a 1-dose rotavirus vaccination program (vs. placebo) and were
ready to submit to science and ethics when GSK came in a bid in the next door province (Ontario) with a
price below what we had calculated to be cost-neutral. As we were able to use the federal purchasing
service and get the vaccine at the same price as Ontario, it was decided to put the study on hold and take
the full-dose RV program using RV1. And there went all our research possibilities. The universal
vaccination program was launched in Quebec on November 1st, 2011 and the uptake seems excellent.
The current RV season has been quite mild so far (and that's using active surveillance!).
Patricia Verhagen's email is: p.bruijning@umcutrecht.nl<mailto:p.bruijning@umcutrecht.nl>
National Health Committee April 2012
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Committee Report number: 2012022
Best of luck in your decisions. Do not hesitate to contact me if I can be of further assistance.
Regards,
Caroline
_________________________________
Caroline Quach, MD MSc FRCPC
Pediatric Infectious Diseases and Medical Microbiologist | The Montreal Children's Hospital
Associate Professor of Pediatrics | McGill University
P +1-514-934-1934 ext. 22620
F +1-514-412-4494
Email: caroline.quach@mcgill.ca<mailto:caroline.quach@mcgill.ca>
On 2012-04-01, at 8:03 PM,
Dear Caroline,
I have recently read with interest an abstract of a paper your co-authored titled " Nosocomial rotavirus
gastroenteritis: Possible impact of a targeted immunization strategy" (2010) in which you suggest that a
targeted rotavirus vaccination program (for specific high risk patients), may be a cost-effective alternative
to universal vaccination.
Following this paper you published another paper in 2011 which concluded that " A rotavirus immunisation
programme targeted at vulnerable patients, such as infants with congenital pathology and low birth weight,
requires assessment in Canada and other countries that have not introduced universal rotavirus
immunisation".
New Zealand is one such country that is yet to implement universal rotavirus vaccination, and I was
wondering whether you were aware of any papers in progress that are assessing a targeted vs universal
approach overseas? We have conducted a fairly comprehensive literature search for papers comparing a
targeted versus universal approach to rotavirus vaccination, but your two papers are the only ones
retrieved that were relevant (and only an abstract was publicly available for the 2010 paper).
Any information (including full text for the 2010 abstract), would be much appreciated.
Kind regards,
National Health Committee
Ministry of Health (New Zealand)
DDI: 04 816 4415
National Health Committee April 2012
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Committee Report number: 2012022
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4.
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6.
7.
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