Building the concept for WHO Evidence Considerations for Vaccine Policy (ECVP): Tuberculosis vaccines intended for adults and adolescents as a test case.

Currently, no formal mechanisms or systematic approaches exist to inform developers of new vaccines of the evidence anticipated to facilitate global policy recommendations, before a vaccine candidate approaches regulatory approval at the end of pre-licensure efficacy studies. Consequently, significant delays may result in vaccine introduction and uptake, while post-licensure data are generated to support a definitive policy decision. To address the uncertainties of the evidence-to-recommendation data needs and to mitigate the risk of delays between vaccine recommendation and use, WHO is evaluating the need for and value of a new strategic alignment tool: Evidence Considerations for Vaccine Policy (ECVP). EVCPs aim to fill a critical current gap by providing early (pre-phase 3 study design) information on the anticipated clinical trial and observational data or evidence that could support WHO and/or policy decision making for new vaccines in priority disease areas. The intent of ECVPs is to inform vaccine developers, funders, and other key stakeholders, facilitating stakeholder alignment in their strategic planning for late stage vaccine development. While ECVPs are envisaged as a tool to support dialogue on evidence needs between regulators and policy makers at the national, regional and global level, development of an ECVP will not preclude or supersede the independent WHO's Strategic Advisory Group of Experts on Immunization (SAGE) evidence to recommendation (EtR) process that is required for all vaccines seeking WHO policy recommendation. Tuberculosis (TB) vaccine candidates intended for use in the adolescent and adult target populations comprise a portfolio of priority vaccines in late-stage clinical development. As such, TB vaccines intended for use in this target population provide a 'test case' to further develop the ECVP concept, and develop the first WHO ECVP considerations guidance.

Shaping markets to benefit global health - A 15-year history and lessons learned from the pentavalent vaccine market.

Market shaping for health products used in lower-income countries strives to benefit public health. As a funder of vaccines, Gavi, The Vaccine Alliance (Gavi) has goals for its market shaping efforts, achieved through a strategy developed and implemented by the Gavi Secretariat, UNICEF, the World Health Organization (WHO) and the Bill & Melinda Gates Foundation (BMGF). A case-study of Gavi's fifteen-year engagement with a vaccine against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenzae type b (pentavalent) provides evidence of the benefits and potential risks of trying to influence markets. During 2001-18, Gavi disbursed US$3.5 billion to support use of 50 million pentavalent doses annually before 2005, increasing to ∼300 million doses annually by 2016. During this time, eight manufacturers invested in vaccine development and manufacturing and the first two manufacturers have subsequently ceased production. Following its strategy, Gavi implemented coordinated market interventions including technical assistance to manufacturers, improving market information transparency, risk-sharing agreements and innovative procurement aiming to stimulate and capitalize on a competitive market. In 2018 supply allows ∼80 million children per year to be immunised, a sixteen-fold increase from 2005, with vaccine-related costs per child for donors and countries of one-quarter the 2005 level. Lessons learned include the importance of frameworks and strategies; the need to adjust interventions with changing conditions; the important role of manufacturers; and the potentially powerful effects of interconnected markets. This case study is limited by its focus on a single health product in a specific market, however the lessons can inform other market shaping efforts when taken in context. While countries and children have improved vaccine access, risks of financial sustainability and continued manufacturer investment in Gavi vaccine markets are being monitored. Gavi should continue implementing a market shaping strategy, adjust with market conditions and expect and measure unintended consequences.