Title: NIHR Global Health Research Group on Evidence to Policy pathway to Immunisation in China (NIHR EPIC), London School of Hygiene & Tropical Medicine
Funder: Department of Health and Social Care

Abstract: 1) Institutional environment LSHTM hosts the largest group of epidemiologists in Europe. It has been one of the main academic providers of research to inform UK vaccination policy for decades, and was awarded a £4m 5-yr grant to run the NIHR HPRU in Immunisation with PHE. LSHTM’s Vaccine Centre has >100 staff working on all aspects of vaccine research. PHE collects and analyses surveillance data on vaccination in England, evaluates the programme’s outcomes and hosts the Secretariat of the Joint Committee on Vaccination and Immunisation (JCVI), the UK’s expert committee on vaccination. Many named EPIC applicants (Jit, Ramsay, Scott, Edmunds, Baguelin) are members and/or regular presenters on JCVI and its subgroups. Although LSHTM and PHE have tremendous strengths in UK vaccine research, they have developed links with China more recently, principally with China CDC and Fudan. These personal links are now sufficiently well-established to propose a collaborative platform to build capacity for evidence-based decision-making on immunisation. China CDC is responsible for infectious disease surveillance, implementing vaccination programmes, conducting research, developing evidence-based guidelines for infectious disease control, and providing scientific evidence to inform immunisation policy by China’s National Health and Family Planning Commission (NHFPC). Fudan is one of China’s top 5 universities, hosts the Laboratory of Public Health Safety of the Ministry of Education and is a main academic provider of applied health and health economics research to inform evidence-based policy. Both organisations seek to strengthen capacity in China for the evidence-to-policy pathway for immunisation. 2) Broad research programme and fit with global health agenda Access to new and underutilised vaccines in low-income countries has dramatically improved since Gavi, the Vaccine Alliance, was launched in 2000. Uptake in middle-income countries has lagged behind because they are mostly not eligible for Gavi support. The prime example is China, where vaccines with universal access in many low-income countries (eg. pneumococcal, influenza and human papillomavirus vaccines) are paid for by users out-of-pocket, leading to inequity in uptake (Hou et al., 2014). The rapid growth of China’s middle class in coastal cities hides huge socioeconomic and health disparities; 150m people live on <$2/day and 180,000 children <5y die each year. These people are underserved by the current vaccine financing policy despite having the highest health burden (Cortez et al., 2014). Licensed vaccines in China are divided into Category I (publicly funded nationwide) and Category II (licensed but not publicly funded). China is considering moving some Category II vaccines to Category I, to maximise health impact particularly for socioeconomically vulnerable people who cannot afford Category II vaccines. Such moves will vastly increase the financial and manufacturing resources needed to supply the large Chinese population. Hence a pre-requisite for funding is evidence of the potential health benefits, budget impact and cost-effectiveness of broader vaccine uptake. In addition, sufficient and reliable public demand for vaccines is needed so that local manufacturers will ensure a reliable vaccine supply. Maintaining public confidence in vaccines is vital in the wake of recent scandals about improperly stored Category II vaccines that have given rise to safety concerns and rumours (Qiu et al., 2016). The UK is a world leader in conducting applied vaccine research and using it in immunisation policy. Our proposed Evidence to Policy pathway to Immunisation in China (EPIC) is a Global Health Research Group that brings the two principal research actors in the UK pathway (LSHTM and PHE) in collaboration with their Chinese counterparts (Fudan and China CDC). EPIC will conduct research directly relevant to supporting policy-makers in making decisions to ensure a reliable, affordable, equitable and uninterrupted supply of vaccines to the Chinese population. EPIC’s structure is inspired by the successful NIHR-funded HPRU in Immunisation, in which LSHTM and PHE jointly conduct research to inform UK vaccine policy. Past discussions about vaccine introduction have focused on evidence of substantial national disease burden (as evidenced by studies in peer reviewed journals), affordability (budget impact), value for money (cost-effectiveness) and an adequate, sustainable supply from local production capacity. Based on these criteria, we will focus research on vaccines against pneumococcus, influenza, Enterovirus A71 and human papillomavirus. Work on these vaccines has the greatest potential to influence policy due to (i) a large and well-defined burden of disease and (ii) potential production capability either because of either local manufacturing or because overseas-manufactured vaccines have been approved for use in China. In the long-term, our ambitions for EPIC’s influence are global. A successful evidence-to-policy pathway in China could inspire similar models in other countries, particularly in Asia. Therefore we intend to seek funding from NIHR and other sources to establish similar arrangements in other Asian countries. Also, inclusion of vaccines in Category II could incentivise vaccine production by domestic manufacturers who can also contribute to global vaccine manufacturing supply. The China Food and Drug Administration has been found to meet World Health Organization standards for vaccine regulatory oversight (Parry, 2014). 3) Short-term (6 month) delivery targets - Signed LSHTM subcontracts with PHE and Fudan. - Signed Fudan subcontract with China CDC. - Meeting in Beijing between Jit, Baguelin and China-based EPIC leads to: (i) consult with Advisory Committee about broad direction and key opportunities to maximise health impact of the work, (ii) plan work with visiting scientists coming to London, (iii) jointly interview prospective PhD students. - Draw up key documents to send to NIHR including (i) detailed timeline for each theme and vaccine drawn up, (ii) clear policy objectives at end-of-grant such as presentation of results to stakeholders. - Applications from PhD candidates for admission to LSHTM in September 2017. 4) Medium-term (1-2 years) targets Theme I: Collect and analyse data about the epidemiology and burden of vaccine-preventable diseases in China. Activities include: - Influenza serological testing of a bank of previously collected blood samples in Anhua county consisting of (i) 1482 paired neonate-mother samples at 0, 2, 4, 6, 12, 24, 35 months and (ii) 665-765 samples each from 1, 2, 3, 4, 5 and 6-9 yr olds sampled before and after winter. - Systematic reviews of disease burden due to pneumococcal disease, influenza and cervical cancer. - Case notes review of patients in five hospitals in different areas of China to collect data on incidence, treatment costs, household costs and health-related quality of life detriment due to pneumococcal disease, severe acute respiratory illness and cervical cancer. - Survey of social contacts relevant to infectious disease transmission from about 1,000 respondents in different regions. Theme II: Understand vaccine supply, demand and decision making among the public, manufacturers and key stakeholders. Activities include: - Project future public demand for Category II vaccines based on surveys and private purchases. - Assess current and future capabilities of manufacturers and of the health system delivery chain (in urban and rural areas) to meet that demand. - Establish a monitoring system for public confidence in vaccines. Theme III: Use findings of Themes I-II to project the health benefits, budget impact, cost-effectiveness and equity impact of vaccination strategies. Activities include: - Model transmission and potential impact of vaccines against pneumococcus, influenza, human papillomavirus and Enterovirus A71. - Estimate budget impact and cost-effectiveness of vaccination strategies, particularly for the highest burdened regions and population subgroups. - Conduct extended cost-effectiveness analyses (Verguet et al., 2014) to examine the impact of public funding of vaccines on household expenditures and catastrophic payments by income quintile. 5) Long-term (2-3 years) targets - Present evidence to key decision makers in order to inform policy making (see “Pathway to impact” for details). - Disseminate lessons learnt and investigate possibilities of similar work elsewhere through articles, presentations, links with organisations and by holding a workshop to key Asian stakeholders in Bangkok. 6) Capacity strengthening and sustainability EPIC will strengthen capacity for vaccine research through joint working. Every project will be jointly conducted by UK and Chinese investigators through (i) UK-based leads (Jit, Baguelin, Larson) and research fellows will spend up to 10% fte in China to jointly set up studies, conduct analyses, meet stakeholders, understand the policy environment and meet students and researchers at China CDC and Fudan, and/or (ii) Chinese-based scientists and PhD students working at LSTHM/PHE in collaboration with UK-based experts. We will also arrange visits by Chinese stakeholders to see development of UK policy briefs by PHE and LSHTM, and observe JCVI sessions which formulate recommendations to the Health Secretary. Visitors will commit to returning to China at the end of their studies to work at China CDC and/or Fudan. China CDC and Fudan commit to continuing these investigations to support future vaccine decisions.

Lay abstract: Many countries have introduced new vaccines against diseases like Streptococcus pneumoniae, influenza and human papillomavirus. In China, many newer vaccines are not centrally funded, so people pay for them out-of-pocket. This makes them inaccessible to poor and vulnerable people predominantly in rural and western parts of China who already have poorer health and difficulty accessing health care. China is investigating whether to increase the range of vaccines that are fully funded by central government. This will require a lot of money and manufacturing capacity to supply China’s large population. Hence, authorities in China need evidence of the potential health benefits, budget impact and value for money of investments in funding new vaccines. In addition, they need to be assured of sufficient and reliable public demand so that local manufacturers will ensure a reliable and uninterrupted vaccine supply. Maintaining public confidence in vaccines is challenging because recent scandals about improperly stored vaccines have given rise to suspicions and rumours about vaccine safety. Our proposed Evidence to Policy pathway to Immunisation in China (EPIC) is a Global Health Research Group that brings four British and Chinese public health and academic partners: the London School of Hygiene & Tropical Medicine (LSHTM), Public Health England (PHE), Chinese Centre for Disease Control and Prevention (China CDC) and Fudan University (Fudan). EPIC’s structure is inspired by the NIHR-funded Health Protection Research Unit in Immunisation, in which LSHTM and PHE jointly conduct research to inform UK vaccine policy. Together, we will conduct applied vaccine research that will help decision makers in China build a vaccination programme that ensures reliable, affordable, equitable and uninterrupted supply of vaccines to the Chinese population. Our work will span three Themes: (i) collecting and analysing data about health and economic consequences of vaccine-preventable diseases in China, (ii) understanding vaccine supply, demand and decision making among the public, manufacturers and key stakeholders, and (iii) using findings from themes (i) and (ii) in mathematical models to project the health and economic impact that vaccine introduction could have, particularly among the groups with the worst health. We will focus research around vaccines that are of most interest to decision makers, but are not currently centrally funded. Every project in EPIC will be a collaboration between the UK and China involving reciprocal exchanges of staff. Scientists in China will draw on British expertise as they design studies to collect and analyse data. Chinese PhD students and visiting scientists will come to LSHTM and PHE and be supervised by UK experts to conduct analyses and build models. British scientists will work with teams in China to gain a deep understanding of vaccine epidemiology, data collection and policy making in China. Findings will be presented to key groups in China responsible for making decisions about vaccine delivery. We aim for EPIC to inspire similar models of research to inform immunisation policy elsewhere in Asia. We will publicise key insights from this collaborative work widely, and hold a workshop in Bangkok towards the end of the grant to share lessons learnt with other Asian countries. Through these channels, we will invite partners outside China to explore funding opportunities to establish similar models in other countries.

Research activity codes: 3.4 VACCINES
Health categories: GENERIC HEALTH RELEVANCE;INFECTION