Suggested citation: Gosnell, G., Braid, E., & Basnak, M. 2023. Vaccine delivery: Timelines and drivers of delay in low- and middle-income countries. Rethink Priorities. [https://rethinkpriorities.org/publications/vaccine-delivery]

Funding statement: We thank Open Philanthropy for commissioning and funding this research report. The views expressed herein are not necessarily endorsed by Open Philanthropy.

Editorial note

This report was produced by Rethink Priorities during February and March 2023. The project was commissioned and supported by Open Philanthropy, which does not necessarily endorse our conclusions. For this report, we investigated the global rollout of six classes of vaccines across the past 70 years, with a special focus on any delays between a vaccine’s initial availability in high-income countries and its widespread availability in low- and middle-income countries. For each vaccine, we have described the rollout process, highlighted key factors contributing to delays, and created timelines of certain milestones to enable comparisons across vaccines. See below for more about our research approach. We have tried to flag major sources of uncertainty in the report, and are open to revising our views based on new information or further research.

Executive summary

Universal introduction of vaccines in low- and middle-income countries (LMICs) has tended to lag behind introductions in high-income countries (HICs). While affordability appears to have been a large source of delay in some cases, the establishment of Gavi appears to have largely alleviated this bottleneck for countries eligible to receive support. Gavi is a global public-private partnership that supports vaccine delivery in LMICs through a variety of initiatives. Gavi support for financing vaccine supplies, developing combination vaccines, and/or coordinating vaccine delivery campaigns appears to have been instrumental in catalyzing the national introduction of vaccines for each of several diseases we consider, including polio, measles, Hib disease, rotavirus, pneumococcal disease, typhoid, and human papilloma virus (HPV). While scrutinizing specific Gavi programs and approaches was outside the scope of this report, the experts we consulted generally agreed that the affordability of vaccines should no longer be a significant barrier to their introduction in LMICs.

While delays between vaccine introduction milestones appear to be shrinking with time, there remain opportunities for improving efficiency and experiences throughout the process. Possible interventions suggested by our research include:

• Improving (accessibility of) evidence on disease burden in LMICs
• Generating robust clinical evidence of effectiveness in LMICs concurrently with evidence generation in HICs
• Designing vaccines to improve uptake and compliance in LMICs (e.g., more multivalent vaccines)
• Improving demand forecasting and implementing market shaping interventions (e.g., long-term or future procurement arrangements, stakeholder coordination, and development of vaccine criteria for manufacturers) to ensure sufficient supply
• Building capacity in LMICs (e.g., adaptability to administer to different age groups)

Experts in vaccine delivery confirmed that the above interventions are worthy of attention, and each expert highlighted the importance of context. In other words, not all solutions will work nor bottlenecks exist for each vaccine or each country, and unique solutions and bottlenecks will arise in different contexts. Several experts therefore encouraged increased involvement of national and subnational/local-level stakeholders to increase understanding of context-specific opportunities (e.g., integration with existing programs and priorities) and constraints (e.g., vaccine culture or crowded vaccine schedules) and improve accountability. Experts also emphasized the need to develop more opportunities for stakeholder learning, particularly for countries to learn from each other and from their own domestic non-health sectors.

Research approach

This research aims to understand whether and at which point(s) there are time gaps between milestones in the process from vaccine development to vaccine delivery in low- and middle-income countries (LMICs). We classify countries as LMICs if they are, or eventually become, eligible for Gavi support.^[1] Similarly, “high-income countries” (HICs) are those that do not eventually become eligible for Gavi support.

The approach we take is to identify the years in which particular milestones were reached for eight vaccines for which VIEW-hub contains data (we exclude Covid-19 vaccines). Open Philanthropy identified the milestones on which we primarily focus:

• Initiation date of first Phase 3 trial
• Date of interim data release from Ph3
• Date of final publication of Ph3
• Date of first approval in a HIC (or by EMA)
• Date of 3rd approval in HIC (or by EMA)
• Date of first WHO prequalification
• Date of first Gavi-eligible country introduction
• Date of Gavi support (if relevant)
• Date of >10M sales in LMICs
• Date of 10th Gavi-eligible country introduction

Note: The early history of the polio, measles, and Hib vaccines dates back to the 1950s-1980s, so some of the information we identified may be less accurate given the more limited data and resources (e.g., ClinicalTrials.gov was not established until 2000, and UNICEF procurement data generally does not precede 1996). Therefore, the precise year of the first Phase 3 clinical trials and their publication, as well as the year when sales thresholds were met, is based on our best guess.

We created a spreadsheet to visualize and compare these timelines, which largely overlap with the written timelines in the following sections of this draft. In many cases, we came across additional milestones that we felt were worth noting, or there were several vaccines for a particular disease and including all information in the written timeline would have made them difficult to follow, so there may be minor discrepancies across the written and visual timelines. For each vaccine, we include what we perceive to be the top causes of delays to LMIC introduction, the written timeline, and a narrative storyline that provides more detail.

To better inform and provide context around our desk research, we conducted interviews with experts within some of the major organizational players involved in vaccine delivery to LMICs. Specifically, we spoke with International Vaccine Access Center (IVAC), Farzana Muhib and Bill Hausdorff at PATH, Lora Shimp at John Snow, Inc. (JSI), and another expert who is not named in this report.

Acknowledgments

Greer Gosnell and Erin Braid were the main authors of this report. Erin Braid edited the client-facing version of the report to transform it into a public-facing report. Melanie Basnak reviewed and supervised this report. Thanks to Adam Papineau for copyediting, to Rachel Norman for assistance with publishing the report online, and to James Hu for formatting assistance. Further thanks to Lora Shimp, Bill Hausdorff, Farzana Muhib, and an unnamed US-based expert for taking the time to speak with us.

1. ^{^}

   Note that Gavi eligibility (currently defined by Gross National Income less than or equal to $1,730; see more about Gavi eligibility here) does not perfectly overlap with World Bank definitions of countries characterized by “low” and “lower-middle” income levels. While all low-income countries (GNI below $1,086) — are eligible for Gavi support, not all middle-income countries (GNI between $1,086 and $4,255) are eligible (World Bank, 2023). Our definition of LMIC for the purpose of this report refers to currently Gavi-eligible countries.