Global Issues in Comparing Vaccination Strategies Dr Lara Wolfson Vaccine Assessment & Monitoring Department of Immunization, Vaccines & Biologicals.
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Global Issues in Comparing Vaccination Strategies Dr Lara Wolfson Vaccine Assessment & Monitoring Department of Immunization, Vaccines & Biologicals Vaccination Strategies: WHO • Overview of work at WHO • Examples of current work • Unmet needs Measuring Mortality and Morbidity 1. 2. 3. 4. Estimates of current disease burden for vaccinepreventable diseases Forecasts of future disease burden & cost-effectiveness under different vaccination scenarios Methods and Materials to assist RO’s and countries in estimation and forecasting of disease burden, introduction of new vaccines, costeffectiveness assessments Support to users of burden of disease data, technical assistance for costeffectiveness Innovation Accelerated Disease Control Immunization Systems Estimating (Total) Mortality at WHO Complete vital registration Age-specific mortality rates DHS and other surveys No recent data UN estimates Incomplete vital registration Sample registration system Censuses Independent studies / reports / models 5q0 45q15 Life tables UN population estimates All-cause mortality envelope by age and sex Epidemiological data from studies, verbal autopsies, WHO programme estimates (child, maternal, injuries, noncommunicable, TB, HIV/AIDS) Cause-specific mortality patterns Country level age, sex and cause specific mortality estimates Vaccine-Preventable Diseases: 24% PertussisTetanus Diphtheria 0.52% 0.37% 0.01% Mening A/C 0.05% Polio JE 0.00%0.02% YF 0.05% Hib 0.68% Rotavirus 0.79% Hepatitis B 1.05% Measles 1.07% Malaria 2.23% Diarrhoea (other) TB 2.37% 2.75% Pneumococcal 2.83% ALRI (Other) 3.56% Other 76.77% HIV 4.87% Causes of 4.1 M Child Deaths, 2002 YF, Diphtheria, Polio, Hepatitis B 0% Malaria 29% Tetanus 5% Pertussis 7% Hib 9% HIV 9% Measles 13% TB 1% Meningococcal A/C, JE <1% Rotavirus 10% Pneumococcal 17% Proportional Mortality Approaches Overall mortality Noninfectious Infectious Diarrhoea ARI Croup Acute bronchitis Pneumonia Viral RSV Bacterial Influenza S. pneumoniae Hib Natural History Approaches Population Susceptible Exposed Infected Hib Unexposed Non infected No access to health care Access to health care Untreated pneumonia Treated pneumonia Bacterial Viral S. pneumoniae Non susceptible Looking at all the sources of data Method 1 Best estimate Method 2 Method 3 Sensitivity analysis General Approach • Get best data/information (literature/grey literature review) • Primary data • Secondary data • Seek expert advise/opinion • natural history of the disease • methods/models • context • Develop consultative process with ROs/countries • Develop best methods/models • Use best assumptions/probabilities • Conduct sensitivity analysis • Validate/check consistency & coherence • Document (explicit & transparent) • Subject to in-house review, then expert review Expected Outputs • Burden of Disease Estimates – By country, age group, sex, year – With estimates of uncertainty, document methods – Country consultation, continuous update of inputs (?!?) • "Scenarios" (aka Comparing Strategies) – Recommendations for best practice – Tools for use at country level – Provide support to advocacy efforts • Cost-Effectiveness – Tools and guidelines, training, support HQ produces burden of disease estimates Publish methods, database Of results, inputs Country clearance Simultaneous Develop scenario models And database of inputs Publish tools Country Requests CEA assistance Develop costing tools and guidelines IF! Targeted Country for Field-testing or Evaluation Collaborate with country On CEA Update annually Publish tools GAVI and the Vaccine Fund • 75 out of 192 member states with GNI <$1000 eligible for support • Immunization Systems Strengthening (ISS) support –performance/reward based system • New Vaccine Support (NVS) – vaccine provided for 1st five years • "Next Window" – 2005-2009 • ICF (Investment Case Framework) The ADIP Paradigm The Example: Measles • Need to develop a method for estimating measles mortality and morbidity • Measure progress towards Measles Mortality Reduction Goal (50% reduction in measles deaths from 1999-2005) • Evaluate the impact of supplemental immunization activities (SIA’s) and routine coverage • Develop a tool for countries to use to estimate their own disease burden and monitor progress "Current" Burden of Measles 1 (1 VE1 MCV1 ) (1 VE1 MCV2 ) Protected Year i = (1 VE1 100% SIAi ) (1 VE1 90% SIAi 1 ) (1 VE1 80% SIAi 2 ) CasesAll Ages Births (1 Protected Year i ) Year i CasesAge Group j Year i DeathsAge Group j Year i Protected <80% Protected >80% Age Group 12% 12% <1 Ages CasesAll Year i 65% 47% 1 to 4 = 18% 25% 5 to 9 4% 11% 10 to 14 1% 5% 15 to 19 CasesAge j CFRAge Group j Year i CFR Literature Review Summary Data (with confidence intervals): 12 to 23 Age Group C ou ntr y ( N ) Ke ny a N =2 Th aila nd N =1 Ethiop ia N =1 Gha na N =1 Guine a- Bis s au N =6 N ig er N =2 Zimba bw e N =1 Se ne ga l N =7 Gamb ia N =6 Malaw i N =2 C ha d N =1 Bu r un di N =1 Ph illipine s N =1 D R C o ng o N =1 My a nma r N =3 N ig er ia N =1 Pe r u N =2 In dia N =3 3 Pa k is tan N =1 Ba ng la de s h N =6 So malia N =1 Za mbia N =1 Mar s ha ll Is la nd s N =1 Sr i L an k a N =2 N ew Ze aland N =1 0 10 20 30 C FR 40 50 869,000 in 1999 to 610,000 in 2002 2.5 2.0 1.5 1.0 0.5 0.0 19 80 19 82 19 84 19 86 19 88 19 90 19 92 19 94 19 96 19 98 20 00 20 02 Millions of Deaths 3.0 Deaths Averted Measles: Comparing Vaccination Strategies in 35 African Countries, 2005-2015 Annual Deaths (thousands) (Thousands) 700 600 500 400 300 200 100 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Constant Routine Constant Routine + 2nd Opportunity Best Estimates Routine Best Estimates Routine + 2nd Opportunity (Project) Reaching 90% Routine Reaching 90% Routine + 2nd Oppportunity SIR Model for 192 Member States dS dS da dt dI dI da dt dR dR da dt where (a, t ) 1 p (a, t ) (a, t ) S (a, t ) (a, t ) S (a, t ) (1 p (a, t )) S (a, t ) (a, t ) S (a, t ) (a, t ) I (a, t ) (a, t ) I (a, t ) (a, t ) I (a, t ) (a, t ) R (a, t ) (1 p (a, t )) S (a, t ) ( a, t ) ( a, t ) The "birth rate" (increase in population) of age a at time t p ( a, t ) The immunization rate of age group a at time t The force of infection for age group a at time t (a, t ) The "death rate" (decrease in population) of age a at time t (a, t ) The death rate (due to all causes) among those infected with measles of age a at time t ( a, t ) The recovery rate for age group a at time t How to calculate R0? t R0,t 1 Popt Casest Immigrant Infections where R0,t R0,t 1 Density t .3 Density t-1 Looking at Scenarios Disease/syndrome Measles - static model Lit review Data extracte d Model develop ed Current Estimat es Estimat es Deaths/ Cases Averted WHO Clearan ce Expert review Methods written partial partial complet ed complet ed complet ed complet ed complet ed completed complet ed complet ed complet ed complet ed complet ed yes NA NA complet ed complet ed Country review process complet ed Manuscript submitted complet ed Measles - SIR model Measles - prop model Pertussis Polio Neonatal tetanus NA completed complet ed Q1 2004 Maternal tetanus Q2 2004 Q2 2004 Q4 2004 Q2 2004 Q2 2004 Q4 2004 Q2 2004 Q2 2004 Q2 2004 Total tetanus Hepatitis B Q1 2004 Q1 2004 Hib meningitis Q3 2004 Hib pneumonia Q1 2004 Q1 2004 Q1 2004 Q3 2004 Q1 2004 Publish ed Q3 2004 Work that is needed (urgently!!) High Priority/Some Work Started • Pneumococcal Disease (Meningitis, Pneumonia) • Rotavirus • Yellow Fever • Rubella/CRS • Diphtheria Lower Priority/Not Started • • • • • • • • • • • • Meningoccocus A/C Japanese Encephalitis Mumps Dengue Typhoid Cholera ETEC Papillomavirus RSV Shigella Streptococcus group A Infant TB CEA Disease Costing Tools Costing studies completed Costing studies in progress Measles Yes Burkina Faso, Kenya, Tanzania, Laos, Zambia, Rwanda Sudan, Nepal, Philippines, Afghanistan, Kazakhstan, Turkey, Kosovo Pakistan Indonesia Neonatal Tetanus Hepatitis B Yes Hib Yes Moscow, Albania, Thailand Rubella In progress Oman, Fiji, Tonga Pneumococcal Yes South Africa, Kenya Polio Rotavirus Mozambique, Mongolia South Africa In progress Ghana Data Collected by the Global Monitoring System (VAM) Incidence and Coverage 1980-2001 (5 yr MA) Complete Incidence Reporting Only Coverage Incide nce 80 10 0 12 0 14 0 16 0 18 0 20 0 100% 90% 80% 70% 60% 50% 40% 60 30% 40 20% 0 20 10% 0% 19 84 19 85 19 86 19 87 19 88 19 89 19 90 19 91 19 92 19 93 19 94 19 95 Incidence per 100,000 Population Aged 0-19 19 96 19 97 19 98 Coverage 19 99 20 00 20 01 Mixed Bag of Needs • Simple tools for use in country to make policy decisions – but validated compared to complex methods. • Valid assessments of current burden of disease (MDG!!) • Guidance on plugging "data holes" • Introduction of new vaccines