Global C-19 Vaccination Strategy – SAGE Extraordinary Meeting

Global C-19 Vaccination Strategy – SAGE Extraordinary meeting

June 29, 2021

Tania Cernuschi Kate O’Brien Sarah Pallas June 29, 2021 Global C-19 Vaccination Strategy SAGE Extraordinary meeting

Objectives Critical appraisal from SAGE will be sought for:

 The Conceptual Goal Framework , built along health and socio-economic dimensions, and the identification of the levels of scientific uncertainty associated with the different steps in the framework

 The Goal Synthesis based on scenario analysis as a means to inform a global strategy

 The lay out of the three potential options for a Global Strategy for 2021-2022

2 June 29, 2021

Agenda

Global C-19 1. Context and proposed goal framework – Kate Vaccination Strategy O’Brien (10’) SAGE Extraordinary 2. Health impact and uncertainties – Sarah Pallas meeting (10’)

3.Goal synthesis and feasibility assessment – Tania Cernuschi (10’)

4. Options for an updated global strategy – Kate O’Brien (10’)

3 June 29, 2021 Over one year since the start of the pandemic, we have a renewed need for collective action

Pandemic status in 2021 Rationale for Updated Goals and Strategy  Epidemiology is dynamic and uneven  Ambitious vaccination coverage targets are being set , however the preconditions, benefits,  Death toll continues to increase risks, and resources needed are not explicit  High transmission is leading to the emergence of new  Uncoordinated approach is further exacerbating variants of concern inequities, and consequent impacts on virus and  We now have the tools to end the acute phase of the disease pandemic, with several vaccines authorized and  Major financial, donor, and political institutions are available in increasing quantities making investment decisions and require strategic global guidance  Manufacturers need enhanced clarity on required supply

“We need to work together. (…) To end the pandemic everywhere, we need a global vaccination plan ” – UN 1. https://iccwbo.org/media-wall/news-speeches/study-shows-vaccine-nationalism-could-cost-rich-countries- Secretary General Antonio Guterres us4-5-trillion/

4 1 Inform the decisions countries are making Updating the Global regarding their vaccination goals and targets Vaccination Strategy for 2022 and beyond

2 Promote an equitable approach to COVID-19 vaccination globally , as part of the broader pandemic control strategy

3 Update global vaccination goals for 2022 , based on specific changes in the global context and in light of key uncertainties

4 Inform global policymaking and access efforts , investment decisions by financial and donor institutions, R&D groups and vaccine manufacturers as well as country planning and programmatic work

5 June 29, 2021 Conceptual goal framework: Socio-economic goals and vaccination Countries are setting health 2022 goals development 1 Priority group vaccination targets defined and socio-economic goals of according to SAGE Roadmap increasing aspiration across a Low Medium High Very continuum high To reach these goals, and hence sustainably lift PHSM, different levels of vaccination ambition are necessary to avoid death Reduce COVID- 3 19 mortality and and suffering 2021 2021 Goal protect health workers 3 For instance, to reduce C-19 Stringent PHSM Less stringent PHSM, Test-Trace-Isolate- TTIQ only, fully leading to lockdown some limitations to Quarantine (TTIQ) and resumed economic mortality and protecting health socio-economic activity travel restrictions only and social activity workers, countries need to and travel increase their vaccination targets, if lifting PHSM PHSM decreasing stringency As they increase their vaccination

Lockdowns Resumed economic and social activity targets, countries can follow the SAGE Roadmap to prioritize Lower Socio-economic goal aspiration level Higher populations

1. Indicative framework as other countries have achieved same goals with different combinations (e.g., China); 3. Maps to SPRP 2021 strategic goals of “Protecting the vulnerable” and “Reducing mortality and Morbidity from all causes”

6 June 29, 2021 Conceptual goal framework: Health dimension Priority group vaccination targets defined according to SAGE Roadmap 2022 goals development 1 Low Medium High Very high Similarly, for each level of

Elimination … PHSM, countries may also Higher Reduce viral wish to increase their transmission 2 health goal aspiration level ,

Reduce COVID- from mortality reduction and 19 disease health system protection to years burden and limit Next 1-2 Next health system reducing viral transmission, impact for instance to reduce Reduce COVID- 3 19 mortality and emergence and transmission 2021 2021 Health goal aspiration level aspiration goal Health Goal protect health of VoCs workers 3 Stringent PHSM Less stringent PHSM, Test-Trace-Isolate- TTIQ only, fully leading to lockdown some limitations to Quarantine (TTIQ) and resumed economic socio-economic activity travel restrictions only and social activity and travel

PHSM decreasing stringency

Lockdowns Resumed economic and social activity

Lower Socio-economic goal aspiration level Higher

1. Indicative framework as other countries have achieved same goals with different combinations (e.g., China); 2. Maps to SPRP 2021 "Suppress transmission" strategic goal; 3. Maps to SPRP 2021 strategic goals of “Protecting the vulnerable” and “Reducing mortality and Morbidity from all causes”

7 June 29, 2021 Conceptual goal framework Priority group vaccination targets defined according to SAGE Roadmap 2022 goals development 1 The framework is intended to help Low Medium High Very high countries move away from setting coverage targets as goal Elimination … Higher in themselves and rather Reduce viral transmission 2 defining explicit health and socio-economic goals and Reduce COVID- working towards equitable 19 disease outcomes for all, both within and years burden and limit Next 1-2 Next health system amongst countries. impact Reduce COVID- 3 19 mortality and The framework is not meant to 2021 2021 Health goal aspiration level aspiration goal Health Goal protect health endorse any specific workers 3 Lower combination of goals and Stringent PHSM Less stringent PHSM, Test-Trace-Isolate- TTIQ only, fully leading to lockdown some limitations to Quarantine (TTIQ) and resumed economic vaccination targets, but rather socio-economic activity travel restrictions only and social activity lay out all the possible options and travel for individual countries and the international community as a

PHSM decreasing stringency whole.

Lockdowns Resumed economic and social activity The framework focuses on vaccination, however must be Lower Socio-economic goal aspiration level Higher considered within the broader Goals (global and countries) to be revisited as the pandemic unfolds and new epi data/information Strategic Preparedness becomes available Response Plan 1. Indicative framework as other countries have achieved same goals with different combinations (e.g., China); 2. Maps to SPRP 2021 "Suppress transmission" strategic goal; 3. Maps to SPRP 2021 strategic goals of “Protecting the vulnerable” and “Reducing mortality and Morbidity from all causes”

8 June 29, 2021 Simplifications adopted for the conceptual framework and analytics

Within their chosen vaccination ambition, countries are encouraged to prioritize priority populations leveraging the SAGE Roadmap

Low=Older adults Medium=All High=Adults + Very high=Include and high-risk groups adults adolescents children

For simplification, we are Age is most consistent risk factor for severe Expanding coverage down to considering age- disease and death across countries and children is a necessary descending prioritization hence chosen as simplifying assumption; implication of reduced in this work age-descending strategy consistent with SAGE transmission goal, or Prioritization Roadmap socioeconomic reopening goal

9 June 29, 2021 Rationale for age cutoffs for global strategy analyses: short answers

Goal Vaccination Age cut-off Short answer ambition adapted for analysis Reduce mortality Low=Older adults 50+  Substantially greater mortality risk above 50 years and high-risk  Lower “older adult” 50+ threshold will (i) capture most adults with groups comorbidities and (ii) be more appropriate cross-country accounting for IFR variability 65+ (e.g., care homes in HICs) and younger demographic structure in LMICs/LICs Reduce disease Medium=All adults 30+  Hospitalization data from a few HIC settings show higher risk and number burden and limit of hospitalizations for those 30+ health system impact Reduce viral High=Adults + 12+  Direct benefit in reducing symptomatic cases, long COVID, and MIS-C transmission adolescents  10-29 years have some of highest pre-pandemic contact rates  12+ cutoff based on vaccines with current/anticipated adolescent indications based on clinical trial ages  Separates decision to vaccinate adolescents vs. younger children Reduce viral Very high=Include 0+  Lifting PHSM increases Rt transmission while children  With higher Rt, it is necessary to vaccinate a larger share of the total lifting PHSM population to achieve viral transmission reduction  Implies expansion to children, especially in LMICs/LICs with younger demographic structures

10 June 29, 2021

Agenda

1. Context and proposed goal framework – Kate Global C-19 Vax O’Brien (10’) Strategy SAGE 2. Health impact and uncertainties – Sarah Pallas Extraordinary meeting (10’)

3.Goal synthesis and feasibility assessment – Tania Cernuschi (10’)

4. Options for an updated global strategy – Kate O’Brien (10’)

11 June 29, 2021 Incremental benefit of vaccination across the health dimension Incremental health benefits with Target population vaccinated over 4 months with PHSM in place (Rt=1.2), gradually lifted thereafter (Rt=3.5) increasing vaccination targets Vaccine efficacy 63% vs infection; 80% vs severe disease; 45% vs transmission to younger ages (assuming Trajectories with and without Deaths averted per Deaths averted per vaccine effective against infection, vaccine population 100 FVP transmission) Deaths per million per day Deaths averted per million total Deaths averted per 100FVP Period population Period 2 (2022-23) Income group: HIC Income group: HIC Distribution of incremental HIC Period 1 (2021-22) +8% benefits reflects demographics 10,000 +20% +7% 3 7,500 2 Age coverage (older populations in HICs, 5,000 target, years 1 2,500 younger populations in LICs), 50+ 0 0 30+ contact patterns, and health Income group: UMIC Income group: UMIC 10+ system strength across countries UMIC 7,500 3 +19% 0+ +14% 5,000 +20% 2 Demonstrates efficiency of 2,500 1 Intervention targeting the oldest age groups 0 0 None in terms of deaths and Vaccine Income group: LMIC Income group: LMIC 7,500 +17% 4 hospitalisations averted LMIC +15% +33% 3 5,000 2 Even a vaccine with “sub-optimal” 2,500 1 efficacy can have substantial 0 0 public health impact Income group: LIC Income group: LIC 7,500 4 +27% +12% 3 LIC 5,000 +41% 2 2,500 1 0 0 50+ 30+ 10+ 0+ 50+ 30+ 10+ 0+ Time, days Age coverage target, years Age coverage target, years

12 Source: Imperial College London, MRC Centre for Global Infectious Disease Analysis, Alexandra Hogan, Peter Winskill, Oliver Watson, Azra Ghani June 29, 2021 Modelled impact of coverage targets by age: LMIC setting

Period Period 1 (2021-22) Period 2 (2022-23) Age coverage target (years) 50+ 30+ 10+ 0+ Vaccinating those <30 years old is an efficient strategy mainly Event: Deaths Event: Hospitalizations Event: Infections

+17% +47% towards the goal of reducing Events averted 7,500 30,000 +15% per population: +33% 100,000 +114% viral transmission LMIC setting 5,000 20,000 75,000 +22% +64% 50,000 +133% 2,500 10,000 +10% Vaccinating younger cohorts 25,000 0 0 0 provides some indirect 50+ 30+ 10+ 0+ 50+ 30+ 10+ 0+ 50+ 30+ 10+ 0+ protection to avert deaths and Events averted 3 8 200 +35% hospitalisations in older age -50% +29% per 100 FVP 6 150 2 -33% -47% +2% cohorts, but efficiency depends on 0% 4 100 -10% +6% 1 vaccine characteristics 2 50

0 0 0 50+ 30+ 10+ 0+ 50+ 30+ 10+ 0+ 50+ 30+ 10+ 0+ Default scenario shown assumes Age Deaths 3,000 same infectiousness of <10 years group in 2,000 and that health system constraints which increase IFR in LMICs/LICs when events 1,000 averted health system is overwhelmed 0

Infec- 3,000 tions 2,000

1,000

0 40-50 60-70 20-30 50-60 80+ 30-40 70-80 80+ 0-10 10-20 20-30 30-40 40-50 50-60 60-70 70-80 80+ 0-10 10-20 20-30 30-40 40-50 50-60 60-70 70-80 80+ 0-10 10-20 30-40 40-50 60-70 70-80 0-10 10-20 20-30 50-60

13 Source: Imperial College London, MRC Centre for Global Infectious Disease Analysis, Alexandra Hogan, Peter Winskill, Oliver Watson, Azra Ghani PHSM lifted at Timing of vaccination 120 days relative to lifting PHSM: LMIC example Prioritization of vaccination, along with an integrated strategy of PHSM use during vaccine • Coloured bars show the total rollout, important to optimize deaths averted if vaccination impact across multiple health begins at that time point dimensions

• Each coloured bar represents Rapid vaccination rollout an increment of around 2 weeks important to minimize economic • The black line shows the costs of PHSM counterfactual epidemic Vaccination needs to happen well in advance of surges to • Only one epidemic wave shown maximize vaccination impact – there would be additional (limited impact of surge response impact on subsequent waves vaccination due to lag in detection and response times)

Still some longer-term benefit to vaccinating “past the peak” for protection against future waves/ waning

14 Source: Imperial College London, MRC Centre for Global Infectious Disease Analysis, Alexandra Hogan, Peter Winskill, Oliver Watson, Azra Ghani Sensitivity analyses: Strategy implications qualitatively similar (LMIC setting example)

Scenario: Default Scenario: Disease-blocking vaccine only Scenario: Default Scenario: Disease-blocking vaccine only

Scenario: Health system unconstrained Scenario: <10 years less infectious Scenario: Health Scenario: <10 years system unconstrained less infectious

Consider changes in timing of epidemic peaks relative to period over which impacts measured

15 Source: Imperial College London, MRC Centre for Global Infectious Disease Analysis, Alexandra Hogan, Peter Winskill, Oliver Watson, Azra Ghani Sensitivity analysis: Potential impacts of VOCs (LMIC setting example)

Default efficacy Lower VOC efficacy Default efficacy Lower VOC efficacy Default Default transmission Default Default transmission High High VOC transmission High High VOC transmission

Default: Vaccine efficacy 63% vs infection; 80% vs severe disease; 45% vs transmission; Rt=3.5 VOC: Vaccine efficacy 40% vs infection; 60% vs severe disease; 33% vs transmission; Rt=4.5

16 Source: Imperial College London, MRC Centre for Global Infectious Disease Analysis, Alexandra Hogan, Peter Winskill, Oliver Watson, Azra Ghani June 29, 2021 Key uncertainties tied to the conceptual framework Priority group vaccination targets defined according to SAGE Roadmap 1 Clinical impact of infection 2022 goals development 1 Low Medium High Very high and disease (e.g., long Elimination … COVID) Higher Reduce viral transmission 2 7 3 2 1 6 7 5 4 3 2 1 6 2 Emergence of VoC Reduce COVID- 19 disease

years burden and limit 1 6 1 6 Next 1-2 Next 3 Vaccine performance in health system impact reducing transmission Reduce COVID- 3 19 mortality and 6 6 4 Safety/efficacy under 12 2021 2021 Health goal aspiration level aspiration goal Health Goal protect health 3 Lower workers years Stringent PHSM Less stringent PHSM, Test-Trace-Isolate- TTIQ only, fully leading to lockdown some limitations to Quarantine (TTIQ) and resumed economic socio-economic activity travel restrictions only and social activity 5 Endemic disease and travel circulation

PHSM decreasing stringency 6 Duration of protection (dealt with through the Lockdowns Resumed economic and social activity scenarios)

Lower Socio-economic goal aspiration level Higher 7 % of population to reduce Goals (global and countries) to be revisited as the pandemic unfolds and new epi data/information becomes available viral transmission 1. Indicative framework as other countries have achieved same goals with different combinations (e.g., China); 2. Maps to SPRP 2021 "Suppress transmission" strategic goal; 3. Maps to SPRP 2021 strategic goals of “Protecting the vulnerable” and “Reducing mortality and Morbidity from all causes”

17 Uncertainty about transmission reduction

• More transmissible VOCs make vaccination-induced “herd immunity threshold” harder to R0=2.7 R0=4.5 achieve

• “Herd immunity threshold ” harder to achieve in younger demographic settings without (i) high proportion of naturally acquired immunity, or (ii) vaccination of younger cohorts

• Uncertainties: • Vaccine effectiveness against infection and transmission across VOCs

• Duration of protection

• Relevance of theoretical “herd immunity threshold” as policy/ • Curves show estimated vaccination coverage required to reach herd immunity threshold for programmatic guide different levels of vaccine effectiveness and naturally-acquired immunity

Source: Figure 2. Hodgson David, Flasche Stefan, Jit Mark, Kucharski Adam J, CMMID COVID-19 Working Group. Euro Surveill. 2021;26(20):pii=2100428. https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428

18 June 29, 2021

Agenda

1. Context and proposed goal framework – Kate Global C-19 Vax O’Brien (10’)

Strategy SAGE 2. Health impact and uncertainties – Sarah Pallas Extraordinary meeting (10’)

3.Goal synthesis and feasibility assessment – Tania Cernuschi (10’)

4. Options for an updated global strategy – Kate O’Brien (10’)

19 June 29, 2021

A Identify countries’ vaccination ambition relative to the framework and progress to date

B Identify barriers on the trajectory towards different goals Goal-synthesis C Perform incremental benefit analysis for moving to higher ambition goals

D Calibrate expectations with respect to global goals

20 June 29, 2021 A. Current country targets mapped against the goal framework Increasing vaccination target xx Country publicly-stated vaccination target as % of total population Countries have been setting goals HICs UMICs LICs/LMICs Low Medium High Very high beyond 20% total pop: goals are Highe Elimination … clustered between 50-75% of total r Reduce viral 12yrs + transmission Desirable direction (implies increasing vax target) 99% 100% population range

Feasible direction (at currently targeted vax level) These translate into very different 80% 80% 90% target ages, with LICs and LMICs 30yrs + 10yrs + having high ambition and targeting 60% Reduce 70% youth

Healthgoal aspiration level 70% COVID-19 35yrs + 73% 79% disease 80% 80% burden and 80% 80% Most countries are probably targeting limit health 40yrs + 64% Next Next 1-2years system 66% resumed socio-economic activity 67% 15yrs + impact 67% 45yrs + 68% while reducing disease burden, but 70% 79% possibly with lack of clarity on how 20yrs + 50yrs + to achieve these Reduce COVID-19 40% mortality and 64% The framework shows how countries’ 69% protect health workers desire to lift PHSM may be 42% 25yrs + 2021Goal 50% constrained by their vaccination 20% 50% 30% 47% 60% target Lower Stringent PHSM leading to lockdown Softer PHSM, some limitations to socio- Test-Trace-Isolate-Quarantine (TTIQ) and TTIQ only, fully resumed economic and economic activity and travel travel restrictions only social activity Higher income countries are PHSM decreasing stringency advancing at much faster pace Lockdowns Resumed economic and social activity towards goals Lower Socio-economic goal aspiration level Higher

21 June 29, 2021 B. Three scenarios for global dose requirements

Disclaimer: It is important to specify that scenarios used in Dose schedule scenario Primary series Booster the analysis were designed to ‘No booster scenario’ Two-dose course primary vaccination No booster explore possible trajectories for HICs and UMICs and one-dose and the resilience of the course primary vaccination for proposed strategy to different LMICs/LICs* types of uncertainty. They do not constitute forecasts by ‘High-risk booster scenario’ Two-dose course primary vaccination Annual one-dose for all countries booster for those WHO or any participating 50+ years only. partners as to the likely Booster every two trajectory of the pandemic nor years for other of any anticipated vaccine populations performance, regulatory or policy decisions. Neither do ‘Yearly booster scenario’ Two-dose course primary vaccination Annual one-dose these scenarios represent for all countries booster for all target populations any judgement by WHO or participating partners about

WHO currently recommends a two-dose course for all vaccines except for J&J, which their relative desirability . requires only one dose. Eventual booster needs have not yet been established

*Low resource requirement scenario requested by African Union for exploratory purposes. 22 June 29, 2021 B. Global programmatic dose requirements per goal and scenario

Aggregate global dose requirement for 2021 and 2022 (bn doses) LICs & Target Scenario HICs UMICs LMICs China India Total Demand considerations 50+ 1,2 1,2 There is a large variance Older adults and Yearly 0,9 in programmatic dose 0,8 0,7 2.8-4.9bn high-risk groups booster requirement across goals 0.8 No booster 0.8 0.6 and scenarios 0,3 0,2 As expected dose 2,3 2,0 1,9 2,1 requirement is 1,6 All adults Yearly 5.4-9.8bn increasing with level of booster goal ambition and 1.3 1.3 1.5 No booster 0.7 0.5 boosters Considerable drop in 3,3 3,0 2,5 2,6 dose requirements in Adults and Yearly 2,3 7.8-13.8bn year 3 in all scenarios . 0+ adolescents booster In no-booster scenario, No booster 1.7 1.9 1.3 2.0 0.9 requirements approach annual birth cohort size 4,3 with important 3,1 3,3 Include children Yearly 2,8 2,7 9.6-16.2bn considerations on booster likelihood of market 2.4 2.3 No booster 2.0 1.8 1.1 investments

Requirements range from 2.8 to 16.2 bn doses

23 Source: COVAX Global Market Assessment June 29, 2021 B. Potential supply - dose requirement for low supply scenario for 2021 and 2022 Incorporating key distribution assumptions based on manufacturing capacity, existing deals, and dose sharing excess supply >20% of demand excess supply between 10-15% of demand excess supply <10% of demand

Scenario HICs UMICs LICs/ LMICs China India Total Target Supply considerations Yearly/high-risk booster – 50+ yrs Older Potential production ranges Global supply may No boooster – adults from 6.5 to 9 bn doses in be adequate over 50+ yrs 2021 and 9 to 17 in 2022 the course of the Yearly booster – No supply constraints for 2021-2022 30+ yrs the ‘older adults + high- biennium, but it will High-risk booster – All risk’ and ‘all adults’ goals require (i) important 30+ yrs adults redistribution in the No booster – For the more ambitious next months as it 30+ yrs goals of ‘adults and builds up and (ii) Yearly booster – adolescents’ and ‘include clear market 12+ yrs children’, all countries signaling for 2022 Adults & High-risk booster – except for HICs face adolesc to sustain the 12+ yrs supply constraints in at ents manufacturing No booster – least one scenario. capacity expansion 12+ yrs There is ~1.5-4.5 bn of (iii) active Yearly booster – currently unreserved management to 0+ yrs manufacturing capacity balance demand and High-risk booster – Include that could be further supply 0+ yrs children secured to address gaps No booster – 0+ yrs

Assumes 2 year programmatic dose requirements are needed by end of 2022, likely over-estimating gaps in supply. ‘No booster scenario’ assumes 1 dose for LICs and LMICs. 24 Source: COVAX Global Market Assessment June 29, 2021 B. Indicative cost to reach different vaccination targets in LICs and LMICs over a two-year period

HW Surge Delivery Procurement Core scenarios Given the wide range of Indicative COVID Vx costs 2021-2022 period LIC/LMIC, USD bn dose requirement scenarios, there is a similarly wide range of costs up to ~60 59 USD bn in 2021-22 8 3 Primary course and booster scenarios are an important driver of cost difference and 31 have long term implications 4 2 47 18 Delivery and HW costs will 2 1 represent ~ 1/4 of overall cost 11 25 1 4 1 15 These costs are only indicative 0 1 8 3 and are under discussion at Scenario: No Scenario: No Scenario: No Scenario: Yearly Scenario: Yearly COVAX CR&D Task Team booster; 50+ years booster; 30+ years booster; 12+ years booster; 30+ years booster; 0+ years

Currently assumes following costs per dose : 6.7 USD for procurement, 0.5 to ~1 USD for delivery costs , decreasing with increasing number of doses, thanks to economies of scale; ~0.9 to ~1.2 USD for HW surge costs , increasing with the number of doses supplied

25 June 29, 2021 B. Important investments have already been made towards ambition vaccination targets

HW Surge Delivery Procurement Core scenarios Important investments have already been made to date Indicative COVID Vx costs2021-2022 period LIC/LMIC, USD bn Categories of investments by COVAX, MDBs, earmarking for bilateral and regional deals, commitments to dose donation Dose donation 59 The commitments already 8 3 Multilateral place LICs and LMICs on a Development good trajectory towards 31 Banks achievement of ambitious 4 targets (12+ and 30+) 2 47 18 2 Sunk cost on Additional funds are 11 1 deals 25 available from MDBs and 1 1 15 8 more ODA could be mobilized, COVAX 2021 Scenario: No Scenario: No Scenario: Scenario: as well as return on booster; 30+ booster; 12+ Yearly Yearly investments from years years booster; 30+ booster; 0+ years years immunization Source: COVAX Country Readiness and Delivery Task Team on global delivery costs for COVID-19 vaccine

26 B. Number of countries and population with potential financial & system challenges by scenario

# countries meeting at # countries meeting at UMIC LMIC LIC XX lest one of the HW or XXX X lest one of three criteria DTP3 criteria

Population, Bn Indicators used to identify countries # countries 1) the cost of vaccinating x% of the population 13 15 28 41 58 is over 1% of 2021-2022 General Government Expenditure* for countries where expected 13 13 15 21 43 government revenue per person vaccinated is less than the cost per person vaccinated 3,0 0 AND/OR 2) the extra HW for vaccinating the target 2,3 population is larger than 10% of existing HW in 1,3 1 countries where the number of physicians/1000 0,9 0 pop is lower than 0.2. 0 0,6 0,5 0,5 0,3 0,2 0,6 0,6 0,7 AND/OR 0,2 0,3 Scenario: Scenario: Scenario: Scenario: Scenario: 3) countries are not able to reach DTP3 No booster; No booster; No booster; Yearly booster; Yearly booster; coverage above 60%** 50+ years 30+ years 12+ years 30+ years 0+ years

*(IMF WEO April 2021 data) 27 ** (WUENIC estimates extracted from WIISE, June 2021) (assumed applicable to 30yrs and 0yrs goals) June 29, 2021 C. Incremental benefits and trade- offs of ambitious vaccination target in LICs and LMICs National considerations Global considerations

Lower/slower vaccination roll out in L(M)ICs could Benefit result in limited control over VOC and lead to  Biggest incremental health benefit of moving to economic losses (due to trade, financial and younger age strata as a result of demographics, consumption patterns) globally mixing patterns and health system constraints  Incremental economic benefits in the form of “Vaccinating 40% globally by end 2021 and GDP losses averted i f vaccination rollout is 60% by first half of 2021 translates into $9 rapid , allowing earlier lifting of economically costly trillion benefits by 2025, with over 40% of PHSM 1 this gain going to advanced economies”

Risk • Inefficient use of scarce resources poses risk to “Our estimates suggest that up to 53% of sustainability of immunization outcomes and new the global economic costs of the pandemic investments across many other diseases of in 2021 [ $1.5-9trillion ] are borne by the considerable burden advanced economies even if they achieve • Risk of increase in cases and IFR universal vaccination in their own countries”

1. Ferranna, Cadarette, Bloom (2021) Harvard School of Public Health

28 June 29, 2021

Agenda

1. Context and proposed goal framework – Kate Global C-19 Vax O’Brien (10’)

Strategy SAGE 2. Health impact and uncertainties – Sarah Pallas Extraordinary meeting (10’)

3.Goal synthesis and feasibility assessment – Tania Cernuschi (10’)

4. Options for an updated global strategy – Kate O’Brien (10’)

29 D. Countries and public health agencies have been setting immunization targets as share of total population

Priority Group Population by Age Strata, mn

Vaccination target mapped to % of total population XX% XX% XX% XX% with priority group coverage assumption XXX 100% %%

Vaccination target mapped to % of total XXX% % XXX% XX XX% X XXX XX% %% 71.8% population w/ 100% coverage assumption X79.5% X 5,594 57.3% 485 51.7% 4,464 465 180 269 37.9% 428 25.4% 413 2,951 403 410 19.4% 369 333 1,512 326 303 266 220 110 614

HW 3 65+ 60-64 55-59 50-54 50+ 45-49 40-44 35-39 30-34 30+ 25-29 20-24 15-19 12-14 12+ 10-11 5-9 0-4 0+ years years years years

Within Priority Group Coverage Assumptions 85% 70% 70% 70% 70% 87% 1

70% 2

1. HICs; 2. UMICs and L(M)ICs 3. Explicitly calculated and subsequently subtracted from their corresponding age group to avoid double-counting

30 Source: UN population estimates, https://population.un.org/wpp/ June 29, 2021 D. Step-wise approach along the trajectory of potential global goals

The path to full global Include recovery advances through Target pop children several goals in a step wise 1 Adults and Global % 70-80% approach adolescents 60% All adults Step 4 Mitigating future health 40% risks (e.g., VoC) for full Older adults Step 3 global recovery and high-risk 2 Minimizing disease burden, 20% directly and indirectly Step 2 advances countries towards Minimizing mortality and resumption of socio- severe disease puts economic activity Step 1 countries on trajectory toward Goal Reducing highest risk of resuming socio-economic description mortality and protecting activity health system limits most severe PHSM needed for crisis response

1. The % population targets include coverage assumptions within the prioritized population: HCW and 65yrs+: 85% coverage, 5-65yrs: 70% coverage, 31 0-4yrs: coverage ranging from 70% to 87% 2. Including all HW June 29, 2021 D. Step-wise approach along the trajectory of potential global goals

The path to full global Include recovery advances through Target pop children several goals in a step wise 1 2 Adults and Global % (range ) 70-80% approach adolescents 60% (47%-64%) Country specific targets need All adults Step 4 to account for local Mitigating future health circumstances , including 40% (22%-50%) risks (e.g., VoC) for full demographic and priority Older adults Step 3 global recovery populations distribution and high-risk 3 Minimizing disease burden, 20% (8%-31%) directly and indirectly Step 2 advances countries towards Minimizing mortality and resumption of socio- severe disease puts economic activity Step 1 countries on trajectory toward Goal Reducing highest risk of resuming socio-economic description mortality and protecting activity health system limits most severe PHSM needed for crisis response

1. The % population targets include coverage assumptions within the prioritized population: HCW and 65yrs+: 85% coverage, 5-65yrs: 70% coverage, 32 0-4yrs: coverage ranging from 70% to 87% 2. Including all HW June 29, 2021 D. Step-wise approach along the trajectory of potential global goals

The path to full global Include recovery advances through Target pop children several goals in a step wise 1 2 Adults and Global % (range ) 70-80% approach from reducing adolescents highest risk of mortality and protecting health systems 60% (47%-64%) limiting most sever PHSM All adults Step 4 needed for crisis response to mitigating future health risks 40% (22%-50%) for full global recovery Older adults Step 3 Unknown impact of VoC and high-risk 3 (vaccine performance, Country specific targets need to account for local 20% (8%-31%) pace of resurgence) Step 2 circumstances , including Target already implemented Unknown trades off of in some UMICs and HICs demographic and priority natural versus vaccine populations distribution Required to resume socio- Unknowns around benefits induced immunity Step 1 Vaccination targets should economic activity of vaccinating adolescents Inadequate be driven by considerations on: Considerations Clear political will to move Requires substantially understanding of mild • Incremental benefits Already established global in this direction, important greater financial and disease, vx safety goal sunk investments programme investment to evidence • Feasibility • Future risks Unfinished agenda well Could be feasible for achieve and requires Requires substantially underway majority of countries with important trade-offs at high greater financial and dose requirement (2 dose + Feasible in all countries external support for programme investment to L(M)ICs at low dose boosters) achieve and requires requirement (1 or 2 dose important trade offs no booster) particularly at high dose requirement

1. The % population targets include coverage assumptions within the prioritized population: HCW and 2. Range refers to the % population in the age strata across HIC, UMIC, LMIC and LIC 33 65yrs+: 85% coverage, 5-65yrs: 70% coverage, 3. Including all HW 0-4yrs: coverage ranging from 70% to 87% June 29, 2021 Options for a Global Strategy for 2021-2022

Global Strategy 3 Older adults (2022)

All adults + Global Strategy 2 risk mitigation (2022)

Global Strategy 1 All (2022)

Include Target pop children 1 2 Adults and Global % (range ) 70-80% adolescents 60% (47%-64%) All adults Step 4 40% (22%-50%) Older adults Step 3 and high-risk 3 20% (8%-31%) Step 2

Step 1

1. The % population targets include coverage assumptions within the prioritized population: HCW and 2. Range refers to the % population in the age strata across HIC, UMIC, 34 65yrs+: 85% coverage, 5-65yrs: 70% coverage, LMIC and LIC 0-4yrs: coverage ranging from 70% to 87% 3. Including all HW June 29, 2021 Key features of the three potential global strategies

Global Strategy 3: Older Global Strategy 2: All adult global Global Strategy 1: Universal global adult global vaccination vaccination with risk mitigation vaccination

• Reduce highest risk of mortality and • Aim to reduce disease burden and putting  Aim to mitigate future health risks for protecting health systems limiting most countries on trajectory toward resuming full global recovery sever PHSM needed for crisis response socio-economic activity Goals

 Focus only on highest risk groups and  Prioritise highest risk groups where incremental  Prioritize older adults and highest risk older adults where incremental benefits benefits are highest, and encourage and groups , but encourage and support all are most certain support countries to all adult populations countries to quickly move to include Age children vaccination

 Reinforce and build on the current • Leverage clear political will and already  Leverage recent ambitious calls for unfinished agenda ongoing in investments, and could be feasible actions and establish equitable  Encourage all countries to await for for majority of countries with external opportunities Alignment support with political further evidence on need/desirability of context further ambitions

• Ensure efficient and effective use of scarce • Promote efficient use of resources in face of • May require massive investments , resources for more feasible and impactful many scientific uncertainties on feasibility and including of external technical support, targets desirability of adolescent and children vaccination to support externally drive, campaign- Requirements • Risk leaving us unprepared in potential • Call for important at-risk investments in type approach to timely immunization in and resource- need for more ambitious vaccination vaccine supply and systems to ensure context of high scientific uncertainty handling targets as more data and knowledge is readiness to implement future steps once scientific • Proposes concomitant investment in collected on scientific uncertainties. uncertainty is cleared other immunization activities and primary care

35 June 29, 2021 Acknowledgements

Members of the Global COVID-19 Vaccination Task Team : Simon Allan, Sunil Kumar Bahl, Mathieu Boniol, Tania Cernuschi, Peter Cowley, Emily Dansereau, Siddhartha Sankar Datta, Isabel de la Mata, Ulla Griffiths, Shanelle Hall, Quamrul Hasan, Joachim Hombach, Hannah Kettler, Olivier Le Polain, Chris Lewis, Richard Mihigo, Nicaise Ndembi, Canice Nolan, Kate O'Brien, Saad Omer, Ahmed Ogwell Ouma, Sarah Pallas, Cuauhtemoc Ruiz-Matus, Yoshihiro Takashima, Nathalie Van de Maele, Charlotte Watts, Yin Zundong Contributing panels and working groups (in no specific order): Global COVID-19 Vaccination Ad-hoc Strategy Group, COVAX global market assessment working group, SAGE Working Group on COVID-19 Vaccines, Imperial College London (MRC Centre for Global Infectious Disease Analysis, WHO Collaborating Centre for Infectious Disease Modelling), Harvard School of Public Health (Value of Vaccination Research Network Secretariat), Country Readiness and Delivery Task Team for Global Delivery Costs, COVAX Workstream Convenors and RSSE

36 June 29, 2021 Global C-19 Vaccination Strategy SAGE Extraordinary meeting

Objectives Critical appraisal from SAGE will be sought for:

 The Goal Synthesis based on scenario analysis as a means to inform a global strategy

 The lay out of the three potential options for a Global Strategy for 2021-2022

37 Appendix: Conceptual goal framework

38 Rationale for age cutoffs for global strategy analyses

Reduce viral Modeling finding: Q3 transmission Maintaining NPIs during vaccination rollout Reduce COVID- minimizes health losses 19 disease burden and limit Q2 Q4 health system Implication: impact Vaccination at each stage of PHSM is Reduce COVID- 19 mortality and Q1 preparatory for next stage of lifting PHSM protect health workers

Stringent PHSM Less stringent PHSM, Test, trace, isolate, TTIQ only, fully leading to lockdown some limitations to quarantine (TTIQ) and resumed economic socio-economic activity travel restrictions only and social activity and travel

Increasing Rt in absence of vaccination

Goal framework key assumption: countries’ primary objective is to “return to normal” (move along horizontal axis) while mitigating health losses No country aims to stay at “stringent PHSM” forever.

39 Age groups vary in their population coverage across income groups

Total Pop Proportion (%) accounted for by Health Goal & Country Income Group (low socioeconomic goal/high PHSM example) • For the first two goals, Average HICs/UMICs would require across higher % total population income Global coverage than LMICs/LICs GOAL HIC UMIC LMIC LIC groups Total due to their older demographic structure Older adults and high-risk groups 31% 23% 14% 8% 19% 19%

All adults 50% 43% 32% 22% 37% 38% Add coverage assumptions we have Adults and adolescents 64% 60% 54% 47% 56% 57% used that get us to this shares Include children 74% 72% 71% 71% 72% 72%

40 Appendix: Health impact modelling

41 June 29, 2021 Timeline to complete Global vaccination work – including consultations

Consultation period

End July Beginning of July Final document Draft available for public 5 June 29 consultation 6 6 6 SAGE review of Early-mid July initial draft 9 June 18 Member State 5 Ad-hoc Strategy consultation Group meeting June 17 SAGE COVID- 19 WG meeting

6 June 10 Member State briefing

42 Modelled impact of coverage targets by age, across income settings (incl. 20+)

Trajectories with and without vaccine Deaths averted per population Deaths averted per 100 FVP

HIC

UMIC

LMIC

LIC

43 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Deaths averted Hospitalisations averted Infections averted Events averted per million population Notes • There is always additional health benefit in vaccinating additional age HIC groups. • Incremental benefit of vaccinating 0+ group highest in lower-income settings due to demography and contact patterns. • Health system constraints are assumed to the present, which is UMIC reflected in the impact in LMIC and LIC settings.

LMIC

LIC

44 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Deaths averted Hospitalisations averted Infections averted Events averted per Notes • Demonstrates efficiency in 100 FVP terms of deaths and HIC hospitalisations averted of targeting the oldest age groups. • Benefit of averting infections shown in vaccinating youngest age groups – particularly in LMIC and UMIC settings UMIC

LMIC

LIC

45 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Interpreting drivers of impact across income settings: deaths with and without vaccine, by age group HIC UMIC LMIC LIC

Pale blue bars: Health System deaths without vaccine Constraints Absent

Health System Constraints Present (default)

Notes • Time period selected such that each bar represents one epidemic wave for comparability • Top row shows health constraints absent : deaths in younger ages in LMICs and LICs are being driven by assumption about health system constraints

46 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Interpreting drivers of impact across income settings: infections with and without vaccine, by age group

HIC UMIC LMIC LIC

Pale blue bars: infections without vaccine

Notes • Time period selected such that each bar represents one epidemic wave for comparability

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London “Matrix” of VOC impact – conceptualised as impact on transmission and impact on vaccine efficacy LMIC setting shown

• Important to consider timing of epidemic peaks and window over which impact is measure (makes it hard to compare)

Default efficacy Lower VOC efficacy Default efficacy Lower VOC efficacy Default Default transmission Default Default transmission High High VOC transmission High High VOC transmission

Default: Vaccine efficacy 63% vs infection; 90% vs severe disease; 45% vs transmission; Rt=3.5 VOC: Vaccine efficacy 40% vs infection; 90% vs severe disease; 33% vs transmission; Rt=4.5

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London “Matrix” of VOC impact – conceptualised as impact on transmission and impact on vaccine efficacy

• Important to consider timing of epidemic peaks and window over which impact is measure (makes it hard to compare)

Default efficacy Lower VOC efficacy Default efficacy Lower VOC efficacy Default Default transmission Default Default transmission High High VOC transmission High High VOC transmission

Default: Vaccine efficacy 63% vs infection; 90% vs severe disease; 45% vs transmission; Rt=3.5 VOC: Vaccine efficacy 40% vs infection; 90% vs severe disease; 33% vs transmission; Rt=4.5

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Sensitivity analyses (shown for LMIC setting with 20+): Deaths averted per million population

Scenario: Default Scenario: Disease-blocking vaccine only Scenario: Default Scenario: Disease-blocking vaccine only

Scenario: Health system unconstrained Scenario: <10 years less infectious Scenario: Health Scenario: <10 years less system infectious unconstrained

• Timing of epidemic peaks shifts with different assumptions • Vaccine that is disease-blocking only (with some reduction in infectiousness for breakthrough infections): few lives saved vaccinating individuals <30 years; slightly higher deaths averted 50+ which is artefact of earlier epidemic and waning immunity • If no constraints on health system, then fewer deaths to avert but similar pattern of incremental gains • If <10 years less infectious, smaller overall incremental impact of vaccinating <10 years.

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Sensitivity analyses (shown for LMIC setting with 20+): Deaths averted per 100 FVP

Scenario: Default Scenario: Disease-blocking vaccine only Scenario: Default Scenario: Disease-blocking vaccine only

Scenario: Health system unconstrained Scenario: <10 years less infectious Scenario: Health Scenario: <10 years less system infectious unconstrained

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Sensitivity to assumptions about take-up within age groups: deaths averted

Optimistic elderly + Pessimistic elderly + Scenario: Default Optimistic elderly pessimistic young younger Notes • Demonstrates importance of maintaining high take-up in the HIC most at-risk populations

UMIC

LMIC

Within priority group 65+ <65 coverage scenario years years Default 85% 70% LIC Optimistic elderly 95% 70% Optimistic elderly + 95% 50% pessimistic younger Pessimistic elderly + 70% 50% pessimistic younger

52 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Sensitivity to assumptions about take-up within age groups: hospitalisations averted

Optimistic elderly + Pessimistic elderly + Scenario: Default Optimistic elderly pessimistic young younger

HIC

UMIC

LMIC

53 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Sensitivity to assumptions about take-up within age groups: infections averted Optimistic elderly + Pessimistic elderly + Scenario: Default Optimistic elderly pessimistic young younger

HIC

UMIC

LMIC

54 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Timing of window of vaccination relative to epidemic peak

Waning immunity following infection (default) Lifelong immunity following infection

Yellow = vaccinated later

Blue/Purple = vaccinated earlier

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London “Matrix” of VOC impact – conceptualised as impact on transmission and impact on vaccine efficacy

Default efficacy Lower VOC efficacy Default Default transmission High High VOC transmission

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London “Matrix” of VOC impact – conceptualised as impact on transmission and impact on vaccine efficacy

Default efficacy Lower VOC efficacy Default Default transmission High High VOC transmission

Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Age groups in which hospitalisations averted for each age coverage targeting strategy Notes Deaths and hospitalisations primarily averted in oldest age groups (where largest severe disease and mortality HIC observed)

UMIC

LMIC

LIC

58 Source: Hogan, Winskill, Watson, Ghani, 2021, Imperial College London Sensitivity analyses (shown for HIC setting): Disease blocking vaccine only Scenario: Default Scenario: Disease-blocking vaccine only