Witold Więcek, Development Innovation Lab, University of Chicago
Amrita Ahuja, Douglas B. Marshall Jr. Family Foundation
Esha Chaudhuri, Department of Economics, University of Chicago
Michael Kremer, Department of Economics, University of Chicago and NBER
Alexandre Simoes Gomes, Development Innovation Lab, University of Chicago
Christopher M. Snyder, Department of Economics, Dartmouth College and NBER
Alex Tabarrok, Department of Economics, George Mason University
Brandon Joel Tan, Department of Economics, Harvard University
Demand for COVID vaccines is still high and distribution has remained uneven around the globe. Ongoing research by a group of scholars led by University of Chicago Professor of Economics and Nobel Prize recipient Michael Kremer explores opportunities for “stretching” existing COVID vaccine supplies — in other words, optimizing dose size, timing, and choice of vaccines to reduce deaths and infections while the world awaits greater production.
Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in a variety of approaches to accelerating vaccination. The authors argue that dose stretching has the potential to boost expansion significantly. Furthermore, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths.
In late 2021, emergence of the Omicron variant of COVID led many countries to accelerate and expand booster programs, due to lower effectiveness of currently available vaccines against Omicron. Some countries have even started to administer fourth doses. This has put additional pressure on supply of vaccines, especially mRNA vaccines, meaning that despite the increased supply, the share of vaccines going to low-income countries has not been growing in recent months. Moreover, if vaccines have to be reformulated against the new variant, the necessary repurposing of vaccine manufacturing will disproportionately affect countries where few people have received primary series vaccinations. The authors suggest that fractional dosing research offers an insurance against potential shocks to supply such as these.
You can find the full article in the Proceedings of the National Academies of Sciences (PNAS) released this week. The abstract is below.
This ongoing research has been coupled with applications underway around the globe:
- WHO SAGE Outreach: The authors have met and presented their work to the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization (SAGE), with follow-up meetings to present evidence coming from new studies.
- DIL Workshop and Updates: In the fall of 2021, the Development Innovation Lab (DIL) at UChicago, led by Professor Kremer, hosted a workshop on fractional dosing, collecting updates from clinical researchers from multiple countries conducting fractional dosing trials for COVID-19 vaccines. The workshop also covered issues relating to trial design and included participants from Belgium, Brazil, Ghana, the Netherlands, Nigeria, Thailand, South Africa, UK and the US. DIL is continuously working to review evidence from fractional dosing trials, available here.
- CEPI Outreach: Professor Kremer has also presented this research to The Coalition for Epidemic Preparedness Innovations (CEPI), which is now pursuing a platform trial of fractional dosing.
- Country Trials – Nigeria: With the support of DIL and the research team and generous support and advice from WAM Foundation, the charitable arm of Weiss Asset Management and Open Philanthropy, a trial is being conducted in Nigeria by the Nigerian Institute of Medical Research, National Institute of Pharmaceutical Research and Development, National Agency for Food and Drug Administration and Control, and the National Primary Health Care Development Agency, in coordination with the Federal Ministry of Health.
PNAS Abstract: Testing fractional doses of COVID-19 vaccines:
Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half- or even quarter-doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public-health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggest strong interest in these approaches.