GAVI Vaccine Investment Strategy

1
GAVI Vaccine Investment Strategy

• Rubella Analysis

Final October 27, 2008
2
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

3
Disease Overview
DISEASE PATHOGEN, TRANSMISSION TARGET
POPULATION1,2

• Rubella is an acute, mildly contagious viral
  disease that produces a distinctive 3-day rash
  and lymphadenopathy (a chronic abnormal
  enlargement of the lymph nodes )
• Only one serotype of rubella virus known
• Transmission
• Humans are the only known hosts for the rubella
  virus
• Rubella is transmitted through the respiratory
  route the period of communicability lasts from
  about 7 days before until 5 days after the rash
  appears
• Transplacental transmission, especially in the
  first trimester of pregnancy, can cause serious
  birth defects (Congenital Rubella Syndrome CRS)
• Geographic distribution
• Rubella has a worldwide distribution, however,
  the extent and periodicity of rubella epidemics
  is highly variable in both developed and
  developing countries (the reasons for this are
  not known)
• Disease Target Population
• Most common among children ages 5 to 9,
  adolescents, and young adults

4
Disease Overview
DISEASE IMPACT2

• Total Morbidity
• Greater than 90,000 cases of Congenital Rubella
  Syndrome (CRS) estimated annually in GAVI
  countries
• Total Mortality
• Neonatal and perinatal deaths associated with
  CRS, but not monitored routinely
• Epidemic Potential
• Both endemic and epidemic
• Worldwide in distribution, rubella flourishes
  during spring (particularly in big cities), and
  epidemics occur sporadically (every 5-9yrs)
• Disease Sequelae
• In children after an incubation period of 16-18
  days, an exanthematous, maculopapular rash erupts
  abruptly
• In adolescents and adults headache, anorexia,
  malaise, low-grade fever, coryza, lymphadenopathy
  and, sometimes, conjunctivitis are the first
  signs and symptoms.
• Complications in the fetus may include deafness,
  cataracts, congenital heart defects, mental
  retardation, microcephaly, and other problems
  miscarriage or stillbirth may also occur

5
Disease Overview
Employ Single Dose Strategy
MEASLES, MUMPS, RUBELLA VACCINATION SUMMARY
MR Measles and Rubella MMR Measles, Mumps
and Rubella MCV Measles Containing Vaccine
6
Disease Overview
DISEASE BURDEN IN GAVI-ELIGIBLE COUNTRIES
MORBIDITY
GAVI Vaccine Investment Strategy Vaccine
Landscape Analysis_Rubella_Apr08
Congenital Rubella Syndrome (CRS) morbidity only
7
Disease Overview
DISEASE BURDEN IN GAVI-ELIGIBLE COUNTRIES
MORTALITY
GAVI Vaccine Investment Strategy Vaccine
Landscape Analysis_Rubella_Apr08
8
Disease Overview
NON-VACCINE PREVENTION TREATMENT INTERVENTIONS9

• Non-Vaccine Preventions
• None
• Treatment Interventions
• Paracetamol for fever and joint pain (until the
  disease has run its course)
• Birth defects caused by CRS, e.g. congenital
  heart defects and cataracts, are treated by
  surgery, early intervention for hearing
  impairment

9
Disease Overview
INEQUITIES9

• Inequity of Poor
• Disproportionately affects the poor due to lack
  of access to better healthcare
• Gender Inequity

10
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

11
Vaccine Landscape
LICENSED MR R VACCINES
12
Vaccine Landscape
LICENSED MMR MMRV VACCINES
assumes MMR or MMRV vaccines will not be adopted
by countries wanting to vaccinate against rubella
13
Vaccine Landscape
ESTIMATED VACCINE AVAILABILITY
R-Vac (R SII) M R (MR SII) MoRu-Viraten
(MR Berna/Crucell) Meruvax II (R
Merck) Tresivac (MMR SII) M-M-R(r)II (MMR
Merck) Priorix (MMR GSK) Priorix-Tetra
(MMRVGSK) ProQuad MMRV (MMRV Merck)
Prior to 2009
2013
2012
2011
2010
2009
assumes MMR or MMRV vaccines will not be adopted
by countries wanting to vaccinate against rubella
14
Vaccine Landscape Analysis
COST EFFECTIVENESS LITERATURE SUMMARY

• Life time cost estimate to treat a child with CRS
  in developing countries is 50,000-60,000/CRS
  child the average GNI in the developing
  countries is 544 (based on World Bank,
  http//ddp-ext.worldbank.org/ext/DDPQQ/showReport.
  do?methodshowReport, 19Nov07)19
• When combined with measles vaccine in countries
  with coverage gt80, the benefits of rubella
  vaccination outweigh the costs (comparable to Hib
  and Hepatitis B vaccines, which are GAVI
  approved)20
• Study by Hinman et al shows that over a 16-21yr
  period, 4M-55M can be saved in a developing
  country (in the English speaking Caribbean)20

15
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

16
Vaccination Policy Strategies
CURRENT POLICY
17
Vaccination Policy Strategies
VISP DECISION FRAMEWORK
Vaccination Strategies for Financial Planning
Purposes
GAVI VIS Decision Framework
Routine Vx Strategy
WCBA Vx Strategy
Catch-Up Vx Strategy
Immunization Objective
15-39yo females
Delayed Impact
None
1yo with MR (2nd dose through routine Vx or
campaigns every 4 yrs)
Control Rubella CRS
Offer Vaccine Financing to GAVI-Eligible Countries
1-19yo
20-29yo females
Rapid Impact
1yo with MR (2nd dose through routine Vx or
campaigns every 4 yrs)
Do Not Support in 2009 - 2013
To prevent accumulation of a pool of
rubella-susceptible persons, the actual strategy
for targeting older children, adolescents, and
women of childbearing age will be decided in each
country based on local epidemiology of
rubella/CRS in consultation with WHO and UNICEF
and in accordance with the most recent WHO
position paper2
18
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

19
Vaccine Need Adoption Forecast
GAVI-ELIGIBLE COUNTRY VACCINE NEED
Vaccine Need 72 VISP Scope 46

• Rubella occurs worldwide with the greatest burden
  of congenital rubella syndrome (CRS) occurring in
  developing countries (WHO position paper, May00)

BLUE Countries with rubella vaccine program in
place (n14) ORANGE countries not eligible based
on projected MCV coverage rates lt80 through 2020
(n12)
Source WHO
20
Vaccine Need Adoption Forecast
INTEGRATED ADOPTION FORECAST
Vaccine Need 72 VISP Scope 46
Bangladesh Bhutan Cambodia Haiti India Mongolia Ne
pal Solomon Is Tajikistan Viet Nam
Lesotho Mali Mozambique PNG Tanzania Timor-Leste Z
imbabwe
Eritrea Ghana Pakistan Rwanda São Tomé and
Principe Uganda
Benin Burkina Faso Kenya Niger Senegal Togo
Indonesia Korea, DPR Myanmar Yemen
Cameroon Congo, DR Côte d'Ivoire Gambia
Congo, Rep. Guinea Sierra Leone
Afghanistan Comoros
Malawi Zambia
Burundi
Djibouti
14 GAVI countries have already adopted rubella
12 are not expected to be eligible based on
projected MCV coverage rates lt 80 through 2020
21
Vaccine Need Adoption Forecast
VACCINE DEMAND GIVEN INTEGRATED ADOPTION FORECAST
Delayed Impact
22
Vaccine Need Adoption Forecast
VACCINE DEMAND GIVEN INTEGRATED ADOPTION FORECAST
Rapid Impact
23
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

24
Vaccine Cost Analysis
ANALYSIS INPUT SUMMARY GENERAL
25
Vaccine Cost Analysis
ANALYSIS INPUT SUMMARY STRATEGY-SPECIFIC
26
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Delayed Impact
• Rapid Impact
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

27
Delayed Impact
KEY OUTPUT SUMMARY Integrated Demand
Forecast 2009-2020
28
Delayed Impact
ANNUAL ANALYSIS RESULTS Integrated Demand
Forecast 2009-2020
29
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Delayed Impact
• Rapid Impact
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

30
Rapid Impact
KEY OUTPUT SUMMARY Integrated Demand
Forecast 2009-2020
31
Rapid Impact
ANNUAL ANALYSIS RESULTS Integrated Demand
Forecast 2009-2020
32
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

33
Implementation Associated Cost Analysis
typical IMPLEMENTATION CHALLENGES
34
Implementation Associated Cost Analysis
UNIQUE IMPLEMENTATION CHALLENGES
35
Implementation Associated Cost Analysis
POTENTIAL IMPLEMENTATION SYNERGIES
Traditional Routine EPI vaccines includes
Baccillus Calmette-Guérin (BCG),
Diphtheria-tetanus-pertussis (DTP) , measles
containing vaccines (MCV), oral polio (OPV),
Tetanus toxoid (TT)

• Vaccine-Specific Synergies
• Leverages traditional EPI systems for routine
  vaccination component
• Avoid incremental cold chain investment given
  switch from measles to MR or MMR
• Expect minimum incremental training costs given
  switch from measles to MR or MMR
• Potential to enhance measles 2nd dose compliance
• Other Synergies
• Potential to integrate with measles disease
  surveillance networks
• Potential to integrate with reproductive and
  maternal health programs
• Potential to integrate with gender-based
  initiatives
• Potential to integrate surveillance for adverse
  events
• Potential to integrate vaccine coverage
  surveillance since they are in the same syringe

36
Implementation Associated Cost Analysis
RELATIVE Cost Assessment
37
Implementation-Associated Cost Analysis
Quantitative Cost Assessment DELAYED impact
WHO GIVS Study Wolfson LJ, Gasse F, et.al.,
WHO, Estimating the costs of achieving the
WHO-UNICEF Global Immunization Vision and
Strategy, 2006-2015, BLT (2008) 86(1)
38
Implementation-Associated Cost Analysis
Quantitative Cost Assessment RAPID impact
WHO GIVS Study Wolfson LJ, Gasse F, et.al.,
WHO, Estimating the costs of achieving the
WHO-UNICEF Global Immunization Vision and
Strategy, 2006-2015, BLT (2008) 86(1)
39
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

40
Analysis Summary
KEY METRIC SUMMARY
41
Rubella
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

42
Key Resources
RUBELLA

• Vaccine Experts
• Peter Strebel, WHO
• Susan Reef, Medical Epidemiologist, CDC
• Maya van den Ent, UNICEF Supply Division
• Yalda Momeni, Contract Officer, UNICEF
• Ed Hoekstra, Senior Health Specialist, Global
  Measles Program Health Emergencies, UNICEF
• Osman Mansoor, Public Health Physician Senior
  Adviser, UNICEF

43
Appendix
REFERENCES (I)

• Plotkin, S, Orenstein, W, Offit, P. Vaccines,
  5th edition, 2008, Chapter 29.
• WHO, Weekly epidemiological record, No. 20, 2000,
  75, 161172.
• WHO, UNICEF 2007 Immunization Summary,
  www.unicef.org/publications/index_38256.html
• Annual WHO/UNICEF Joint Reporting Form and WHO
  Regional offices reports, updated Dec07 (also,
  Personal communication with WHO
  www.who.int/immunization_monitoring/routine/immuni
  zation_coverage/en/index4.html
• Morbiditynumber of new cases of rubella in a
  given year
• http//web.gideononline.com (EBM Evidence Based
  Medicine database, sources from WHO, PubMED,
  ProMED, etc)
• Morbidity Rate Morbidity / (Total Population)
  x 100,000 where Total Population sourced from
  (UN Population Division, World Population
  Prospects The 2006 revision population
  database, esa.un.org/unpp/index.asp?panel2, 2005
  Total Population)
• Mortality Rate Mortality / (Total Population) x
  1,000,000
• Plotkin, S, Orenstein, W, Offit, P. Vaccines,
  5th edition, 2008, Chapter 29.
• www.seruminstitute.com/content/products/product_me
  asles_rubella.htm
• www.seruminstitute.com/content/products/product_rv
  ac.htm

44
Appendix
REFERENCES (IV)

• www.rxmed.com/b.main/b2.pharmaceutical/b2.prescrib
  e.html and www.novaccine.com/specific-vaccines/vac
  cine.asp?v_id34
• www.fda.gov/cber/products/meruvax.htm (SII makes
  a similar vaccine under the brand name R-VAC)
• Merck, www.merckvaccines.com/srv/gw/home/desktop.j
  sp?frame1 (Per letter 07Mar08 ProQuad is
  unavailable due to manufacturing issue and is
  unrelated to postmarketing analyses or any safety
  or efficacy issue with the vaccine. Expects to
  bring ProQuad back to US market in early 2009)
• www.spmsd.co.uk/upload/public/Files/8/Current-MMRI
  I_API-UK-05-2007.pdf www.merckvaccines.com/mmrPr
  oductPage_frmst.html
• www.gsk.com.au/products_vaccines_detail.aspx?view
  31
• www.clinicaltrials.gov (NCT00353288)
• www.seruminstitute.com/content/products/product_tr
  esivac.htm personal communication with S. Reef
  (CDC)
• Hinman et al, Bull WHO, 2002, 80264-270
  (www.who.int/bulletin/archives/80(4)264.pdf)
• WHO, Weekly epidemiological report, No. 20, 2000,
  75, 161172 Hinman et al, Bull WHO, 2002,
  80264-270