WHO's Immunization Policy Framework: Is it achieving its goals? : Professor Helen Rees Chairperson, WHO’s Strategic Advisory Group of Experts (SAGE) Wits Reproductive Health and HIV Institute, South Africa Global Vaccines 202X, Philadelphia, May 2011

Civil Society and Immunization Policy Who do we trust?

About the World and Vaccines Lets take a lesson from HIV Grassroots activism in developing and developed worlds Political pressure Global Pharma partnerships about costs Mobilising resources Global impact being internationally watched The Vaccine world Lacks grassroots activism Programmes been mostly top down, taken for granted Enthusiasts work with each other within the vaccine world Pharma a major player but more transparency about costing required Threatened by vaccine hesitancy and weak health services

About WHO WHO is the directing and coordinating authority for health within the United Nations system. In the 21st century, health is a shared responsibility, involving equitable access to essential care and collective defence against transnational threats. It is responsible for providing leadership on global health matters Shaping the health research agenda Setting norms and standards Articulating evidence-based policy options Providing technical support to countries Monitoring and assessing health trends.

WHO’s challenge There is no substitute for the WHO, with its progressive constitution and global legitimacy. It is not likely that the same powers would be granted to an international organization if it were created today. Consequently, while remaining true to its normative and bold vision of health for all, the WHO must adapt to a new political climate, demonstrate global leadership, and deliver results.

A critical appraisal of WHO’s immunization policy framework Can we trust them? I think so, they go to lots of meetings…

Immunization Policy Advisory Framework Countries Other WHO Technical Advisory Committees Global policy recommendations & strategies Support regional/national challenges Regional Technical Advisory Group Strategic Advisory Group of Experts (SAGE) Regional policies & strategies Identify & set regional priorities Monitor regional progress National Policies & Strategies Prioritize problems & define optimal solutions Implement national programme & monitor impact National Technical Advisory Group on Immunization Safety Standards Practice Burden assessment/ modelling

Strategic Advisory Group of Experts (SAGE)  Principal advisory group to WHO for vaccines and immunization: from research to delivery of immunization and linkages with other health interventions - all vaccines, all ages  Reports directly to WHO’s Director General and involves all relevant WHO departments  Restructured in 2005 in context of Global Immunization Vision and Strategy

Strategic Advisory Group of Experts (SAGE)  Membership -15 members  Individual capacity and broad range of expertise  Balance of professional affiliation, area of interest, geographic representation  Declarations of interest  Appointed by WHO DG upon recommendation of external selection panel  Rotation  Reappointment subject to participation/contribution and review by selection panel  Public call for nominations

Strategic Advisory Group of Experts (SAGE) Meetings and operational procedures –Two meetings a year (April and Nov) –Two preparatory teleconferences for each meeting –Only plenary sessions – transparent process –Extensive representation from key partner organizations –Experts invited as needed –Evidence-based –Background documents web and Yellow Book –Tracking sheet for follow-up on implementation of recommendations –Working groups –Agenda setting Strong links with Regional Technical Advisory Groups Report and communications

SAGE working groups Establishment and ToRs decided by WHO and SAGE members Composition –Public call for nominations –At least two SAGE members & additional experts –Declaration of interests To review evidence and address specific issues in great depth and prepare for fruitful discussions at SAGE when issue is complex Not allowed to make decisions or speak on behalf of SAGE Time limited Currently 8 active working groups

Agenda developed in consultation with SAGE members, other HQ departments, regional offices, stakeholders and countries Two year horizon Due diligence but need for sufficient evidence and preparation including working groups, other technical advisory groups or other committees Expected output For DECISION, DISCUSSION, or INFORMATION Search engine for topics previously discussed SAGE Agenda-setting process

Issues taken into consideration by SAGE in the development of recommendations Disease epidemiology –Disease burden including age specific mortality, morbidity, and societal impact; specific risk groups; epidemic potential; disease occurrence over time; serogroup or serotype distribution; and changes in epidemiology over time Clinical characteristics –Clinical management of disease, disease severity, primary/secondary/tertiary care implications, long term complications of disease and medical requirements Evidence-based recommendations based on GRADing system

Issues taken into consideration by SAGE in the development of recommendations Vaccine and immunization characteristics efficacy, effectiveness and population impact of vaccine; vaccine safety; indirect protective effects or safety concerns; cold chain and logistics concerns; vaccine availability; vaccine schedules; schedules social and programmatic acceptability, ability to monitor program impact Economic considerations disease, vaccine and vaccine delivery costs, potential for vaccine price reduction, vaccine cost and cost-effectiveness of immunization programmes, and affordability of immunization Health system opportunities and existence of and interaction with other existing intervention and control strategies Social impact Legal considerations Ethical considerations

Is SAGE delivering on Access, Equity & Ethics? Transparent, public appointment process Declaration of interests Regional representation on SAGE & Regional viewpoints Open plenaries & transparent decision making Public access to decisions Best evidence-based recommendations Impact: –Usefulness –Communication and access –Credibility Guided by equity, ethics and access

SAGE Agenda: April 2011 meeting SPECIFIC TOPICS Pandemic and seasonal influenza vaccines Tick-borne encephalitis Meningococcal meningitis vaccines Rubella vaccination immunization schedules Polio eradication Update of evidence-based review process and GRADing of quality of scientific evidence Cholera vaccine RUNNING ITEMS Global progress & implementation of recommendations Regional reports Reports from other Immunization Advisory Committees - Advisory Committee of the Initiative for Vaccine Research - Global Advisory Committee on Vaccines Safety Report from the GAVI Alliance

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries MeningitisSuccess of meningococcal A conjugate vaccine in African meningitis belt Need to strengthen surveillance World did not ignore disease outbreaks specific to poor countries

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries MeningitisSuccess of meningococcal A conjugate vaccine in African meningitis belt Need to strengthen surveillance World did not ignore disease outbreaks specific to poor countries Tick-borne encephalitis Acknowledge limited information on boosters but allowed endemic countries to continue with this. Need for more clinical data on boosters noting high costs

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries MeningitisSuccess of meningococcal A conjugate vaccine in African meningitis belt Need to strengthen surveillance World did not ignore disease outbreaks specific to poor countries Tick-borne encephalitis Acknowledge limited information on boosters but allowed endemic countries to continue with this. Need for more clinical data on boosters noting high costs CholeraStockpiles for emergencies and for endemic countries Who pays for stockpiles and are they used for endemic or emergency scenarios? Use of cholera in emergencies

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries MeningitisSuccess of meningococcal A conjugate vaccine in African meningitis belt Need to strengthen surveillance World did not ignore disease outbreaks specific to poor countries Tick-borne encephalitis Acknowledge limited information on boosters but allowed endemic countries to continue with this. Need for more clinical data on boosters noting high costs CholeraStockpiles for emergencies and for endemic countries Who pays for stockpiles and are they used for endemic or emergency scenarios? Use of cholera in emergencies PolioAffordable IPV vaccines for post- eradication Global eradication effortsDoes polio divert energy from routine immunization

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries MeningitisSuccess of meningococcal A conjugate vaccine in African meningitis belt Need to strengthen surveillance World did not ignore disease outbreaks specific to poor countries Tick-borne encephalitis Acknowledge limited information on boosters but allowed endemic countries to continue with this. Need for more clinical data on boosters noting high costs CholeraStockpiles for emergencies and for endemic countries Who pays for stockpiles and are they used for endemic or emergency scenarios? Use of cholera in emergencies PolioAffordable IPV vaccines for post- eradication Global eradication effortsDoes polio divert energy from routine immunization InfluenzaLimited information about epidemiology in LIC, LMIC. Stockpiles for developing countries Safety messaging to developing countries about narcolepsy Limited access to H1N1 vaccines in LIC and LMIC during pandemic response. Stockpiles.

TopicAccessEquityEthics RubellaPiggy back on measles elimination efforts Noted the stark difference between Africa and other regions in rollout. Modelling allowed recommendations to cater for poorest functioning EPI programmes 42 years later rubella vaccine still not available in Africa and other developing countries MeningitisSuccess of meningococcal A conjugate vaccine in African meningitis belt Need to strengthen surveillance World did not ignore disease outbreaks specific to poor countries Tick-borne encephalitis Acknowledge limited information on boosters but allowed endemic countries to continue with this. Need for more clinical data on boosters noting high costs CholeraStockpiles for emergencies and for endemic countries Who pays for stockpiles and are they used for endemic or emergency scenarios? Use of cholera in emergencies PolioAffordable IPV vaccines for post- eradication Global eradication effortsDoes polio divert energy from routine immunization InfluenzaLimited information about epidemiology in LIC, LMIC. Stockpiles for developing countries Safety messaging to developing countries about narcolepsy Limited access to H1N1 vaccines in LIC and LMIC during pandemic response

Access, Equity, Ethics in new SAGE agenda items AccessEquityEthics Use of vaccines in humanitarian emergencies Strengthening surveillance networks Accessibility to affordable vaccines Vaccine-hesitant populations Use of vaccines in immunocompromised populations

AccessEquityEthics Optimizing immunization schedules Impact of introduction of new vaccines on immunization and health systems Maternal immunization to enhance the protection of mothers and infants Involvement of the private sector The unimmunized and partially immunized child Strengthening health services

Immunization Policy Advisory Framework Countries Other WHO Technical Advisory Committees Global policy recommendations & strategies Support regional/national challenges Regional Technical Advisory Group Strategic Advisory Group of Experts (SAGE) Regional policies & strategies Identify & set regional priorities Monitor regional progress National Policies & Strategies Prioritize problems & define optimal solutions Implement national programme & monitor impact National Technical Advisory Group on Immunization Safety Standards Practice Burden assessment/ modelling

Regional Technical Advisory Group Critically important to adapt SAGE recommendations Depends on high calibre staff and TAG appointees Depends on good understanding and coordination between regional TAGS & regional offices TAG and office staff should be selected on technical merit not on other criteria Need the ‘ear’ of health ministers Limited resources (human and financial) to fulfil tasks Regional policies & strategies Identify & set regional priorities Monitor regional progress Have a lot of autonomy

National Immunization Technical Advisory Groups (NITAGS) National Policies and Strategies Prioritize problems and define optimal solutions Implement national programme and monitor impact Have a lot of autonomy

National Immunization Technical Advisory Groups (NITAGS) Scarce skilled human resources in many countries, CoIs Advisory and lack teeth unless empowered by health minister Need local budgets Not seen as priority to support EPI in many countries Important to interpret SAGE recommendations at local level May not be possible to have meaningful NITAGS in all countries making regional role important National Policies and Strategies Prioritize problems and define optimal solutions Implement national programme and monitor impact Have a lot of autonomy

SAGE Challenges Continuous evaluation & adjustments Declaration of interests Heavy work burden for members Increased credibility and visibility  increased demands and pressure Processes quite cumbersome Funding for SAGE core activities Understaffed and dependent on few excellent staff

Thank you With thanks to Phil Duclos, IVB

WHO vaccine position papers Position papers = Key reference documents Available in all official languages Convergence of other WHO documents (International Travel and Health, Essential Drugs List, …) Developmental and review process (SAGE, extensive peer review, evidence-base, periodic updating) Format Weekly Epidemiological Record Current structure (Intro, background (Disease epidemiology, the pathogen, disease), info on vaccines (composition, safety, immune response, efficacy and effectiveness, cost effectiveness and any other relevant issue), WHO position on vaccine use) Additional posting of information on the web: GRADing tables, references, summaries (one pager and PowerPoint presentation)

Pathways for WHO recommendations on vaccine use SAGE Relevant existing technical advisory committee Background Paper Global Advisory Committee on Vaccine Safety Expert committee on Biological Standardization Regional TAGS & NITAGS Regional consultations WHO Position Paper WHO DG Secretariat SAGE working group Input Request for review of evidence Country Decision making Recommendations Other relevant non immunization related WHO policy recommendation making body Quantitative Immunization and Vaccines related Research Advisory Committee Industry and other partners Immunization Practices Advisory Committee

Priority topics for SAGE meetings identified through a survey of SAGE members Use of vaccines in humanitarian emergencies Strengthening surveillance networks Accessibility to affordable vaccines Communication with vaccine-hesitant populations Validation of coverage Use of vaccines in immunocompromised populations

Optimizing immunization schedules Impact of introduction of new vaccines on immunization and health systems Maternal immunization to enhance the protection of mothers and infants Involvement of the private sector Strengthening of national technical advisory groups on immunization (NITAGs). Priority topics for SAGE meetings identified through a survey of SAGE members

Challenges Continuous evaluation & adjustments Declaration of interests Heavy work burden for members Increased credibility and visibility  increased demands and pressure Processes quite cumbersome Funding for SAGE core activities Technical contribution and coordination

Challenges Importance of regional offices and Advisory Committees in the adaptation of the SAGE recommendations Weakness of NITAGS Advisory nature of NITAGS means that recommendations can be ignored Financial sustainability for countries to implement Weakness of health services Vaccine hesitancy

Resources requirements Staff Core Senior health officer Technical assistant (currently missing) Administrative assistant Web assistant, documentalist, clerk, and communication officer (part time) Specific technical contribution Resources excluding salaries US$ 700K +

Quality of evidenceQuality starting factor is first assigned base on Study Design Quality score is lowered 1 ifQuality score is raised 1 if We are very confident that the true effect lies close to that of the estimate of effect on health outcome (4) Randomised trials1)Limitation of design: 2 -1 Serious -2 Very serious 2)Inconsistency: -1 Serious -2 Very serious 3)Indirectness: 2 -1 Serious -2 Very serious 4)Imprecision: -1 Serious -2 Very serious 5)Publication Bias: -1 Likely -2 Very likely 1)Large effect: +1 RR or OR>2 (or <0.5) in 2+ studies +2 RR or OR >5 (or <0.2) in 2+ studies 2)Dose response (population based): +1 Evidence of decreased risk with increased vaccine coverage including evidence of reversal at population level (disease returns when vaccine coverage is decreased) population based dose response +2 Very strong evidence of decreased risk with increased coverage 3)Antagonistic bias and confounding: +1 All major confounders would have reduced the effect or +1 Ability of design to control for confounding and avoid biases +2 If in addition to design, consistency across different settings, different investigators, and possibly different designs We are moderately confident in the estimate of effect on health outcome: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different (3) Our confidence in the estimate of the effect on the health outcome is limited: The true effect may be substantially different from the estimate of the effect (2) Observational studies, disease surveillance and post market safety surveillance data We have very little confidence in the estimate of the effect on the health outcome. The true effect is likely to be substantially different from the estimate of effect (1) 1 1= move up or down one grade (for example from high to intermediate), 2= move up or down two grades (for example from low to high) 2 Should be commensurate with study design

SAGE: Drivers? Best evidence-based recommendations Impact Usefulness Communication and access Credibility Continuous enhancement of processes as a result of feed-back and external reviews

Declaration of interests Prior to appointment on committee and updating before each meeting Discussion with Chair Public disclosure of DOI and short biography posted on web Additional guidelines on assessing SAGE members' DOI and framework on how to write public disclosure Lot of work for secretariat DOI one element only of credibility and process to avoid conflicts of interest