Speed Versus Efficacy: Quantifying Potential Tradeoffs in COVID-19 Vaccine Deployment
Authors: A. David Paltiel, Amy Zheng, Jason L. Schwartz
Journal: Annals of Internal Medicine (2021)

Letters5 January 2021Speed Versus Efficacy: Quantifying Potential Tradeoffs in COVID-19 Vaccine DeploymentFREECorrection(s) for this article:CorrectionsMay 2021Correction: Quantifying Potential Tradeoffs in COVID-19 Vaccine DeploymentFREEA. David Paltiel, PhD, Amy Zheng, BA, and Jason L. Schwartz, PhDA. David Paltiel, PhDYale School of Public Health, New Haven, Connecticut, Amy Zheng, BAHarvard Medical School, Boston, Massachusetts, and Jason L. Schwartz, PhDYale School of Public Health, New Haven, ConnecticutAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-7866 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: The global effort to develop a vaccine for coronavirus disease 2019 (COVID-19) has already produced 2 candidates, each requiring 2 doses, with reported efficacies exceeding 90% (1). The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization for both vaccines (Pfizer-BioNTech and Moderna). Their reported efficacies greatly exceed the 50% threshold the FDA cited in a June 2020 guidance document (2). Additional vaccine candidates at earlier stages of development hold the promise of single dosing, simpler storage requirements, and more rapid immunity after vaccination (3).The availability of multiple vaccine options would be a welcome development but would create policy dilemmas. How do we define the "best" vaccine, and which populations should receive it? Should the FDA expect all candidates to meet or exceed the 90% efficacy benchmark established by the 2 frontrunners? From a population perspective, how good is "good enough"? Given that some portion of the population will inevitably fail to return for a second dose, might a single-dose vaccine that is 75% effective and takes 2 weeks to achieve protection better contain the pandemic than a 95%-effective vaccine requiring 2 doses and a 4-week lag before full efficacy?Objective: To quantify the speed-versus-efficacy tradeoff using a previously published model of a COVID-19 vaccination program (4). The model accounts for transmission of severe acute respiratory syndrome coronavirus 2, COVID-19 disease severity, and recovery or vaccination leading to protective immunity. Modifying parameters related to vaccine efficacy, vaccination program scale-up and coverage, and the time to vaccine benefits, we compared the likely performance of 1- and 2-dose vaccine candidates over a 6-month horizon on outcomes of cumulative infections, deaths, and peak hospitalizations.Methods and Findings: Consistent with the FDA efficacy definition, we assumed that a 2-dose vaccine produced a 95% decrease in rates of progression to symptomatic disease, to severe or critical disease from mild disease, and to COVID-19–related death, as well as a nearly 3-fold increase in rates of disease recovery. We further assumed that this vaccine had a 0.5% daily uptake, double the observed peak rate for influenza vaccination in the United States (4), and took 4 weeks to achieve lifetime protection, allowing for partial immunity after the first dose. We compared this vaccine with 2 hypothetical, single-dose alternatives, one conferring lifetime protection and the other with stable efficacy of uncertain duration (exponentially distributed with a mean duration of 6 months). Both of these single-dose vaccines were assumed to achieve more rapid daily uptake (0.75%) and to take effect 14 days after administration. We considered efficacies for both single-dose vaccines ranging from 0% to 100%.We did the base analysis in the context of an epidemic with an effective reproductive number (Rt) of 1.8. Other inputs were obtained from published sources, particularly the guidance for COVID-19 model parameterization from the Centers for Disease Control and Prevention and the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (4, 5).In this model, a single-dose vaccine conferring lifetime protection need only attain an efficacy of 55% to avert as many infections as a 2-dose vaccine with 95% efficacy (Figure [top], blue crossing orange line). However, the single-dose vaccine with an uncertain duration of protection (mean, 6 months; yellow line) would need to attain 75% efficacy to avert the same number of infections. Similar mortality outcomes (Figure, bottom) can be achieved at single-dose efficacy levels of 40% (lifetime) and 60% (uncertain). Under more severe epidemic assumptions (Rt = 2.1), the single-dose vaccine at lower efficacy levels of 50% (lifetime) and 70% (uncertain) would prevent as many infections as a 2-dose vaccine with 95% effectiveness. Parity of mortality outcomes would be achieved at single-dose efficacy levels of 30% (lifetime) and 45% (uncertain). The single-dose vaccine could also achieve outcome parity at lower efficacy if the challenges of administering a 2-dose vaccination series reduced coverage.Figure. Comparison of vaccine performance.The figures illustrate the performance of 4 vaccination strategies in 100 000 persons with 0.1% infected and 9000 recovered in a susceptible–exposed–infectious–recovered model: 1) no vaccination (gray line); 2) a 95%-effective, 2-dose vaccine (orange line); 3) a single-dose vaccine conferring lifetime protection (blue line); and 4) a single-dose vaccine conferring an uncertain duration of protection that is exponentially distributed with a mean of 6 mo (yellow line). The vertical axes represent the outcome of interest (cumulative infections [top] and deaths [bottom]). The horizontal axes denote the efficacy of the single-dose vaccine. The crossing point of the blue line with the orange and yellow lines denotes the efficacy levels at which the 2 single-dose vaccines match the performance of the 95%-effective, 2-dose comparator. Download figure Download PowerPoint Discussion: Prior work has shown that the success of a COVID-19 vaccination program will depend more on the speed and reach of its implementation than on the efficacy of the vaccine itself (4). The analysis presented here highlights the steep clinical and epidemiologic costs imposed by a 2-dose vaccination series in the context of ongoing pandemic response. Depending on the duration of protection conferred—and, of note, considering only a 6-month time horizon—a single-dose vaccine with 55% effectiveness may confer greater population benefit than a 95%-effective vaccine requiring 2 doses. This suggests that now that a highly effective, 2-dose vaccine for COVID-19 has been authorized and vaccination programs have begun, sustained and aggressive investment in pursuit of faster-acting, more convenient, 1-dose vaccine candidates remains justified.References1. Weiland N, Grady D, Zimmer C. Moderna vaccine is highly protective against Covid-19, the F.D.A. finds. New York Times. 15 December 2020. Accessed at www.nytimes.com/2020/12/15/health/covid-moderna-vaccine.html on 16 December 2020. Google Scholar2. U.S. Food and Drug Administration. Development and licensure of vaccines to prevent COVID-19: guidance for industry. 30 June 2020. Accessed at www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19 on 16 December 2020. Google Scholar3. Corum J, Wee S, Zimmer C. Coronavirus vaccine tracker. New York Times. 2 December 2020. Accessed at www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html on 16 December 2020. Google Scholar4. Paltiel AD, Schwartz JL, Zheng A, et al. Clinical outcomes of a COVID-19 vaccine: implementation over efficacy. Health Aff (Millwood). 2020:101377hlthaff202002054. [PMID: 33211536] doi:10.1377/hlthaff.2020.02054 Google Scholar5. Centers for Disease Control and Prevention. COVID-19 pandemic planning scenarios. 10 September 2020. Accessed at www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html on 16 December 2020. Google Scholar Comments0 CommentsSign In to Submit A Comment Sergio StagnaroQuantum Biophysical Semeiotic Research Laboratory5 January 2021 An unknown secondary effect of vaccination for Covid-19. Sirs, Author of Psychokinetic Diagnostics (1-3), I would like to point out the persistent microcirculatory reaction in the limbic system, particularly in hippocampus, which began immediately after the inoculation of anti-coronavirus vaccine (I have studied Pfizer, Sputnic V, and Astra-Zeneca), I've observed in 15 vaccinated people, chosen at random, in Italy. The coronavirus vaccination immediately brings about a persistent microcirculatory activation of the limbic system, i.e. Brain Sensors (4, 5). This fact indicates that the human body of the vaccinated subject reacts intensely to the arrival of a harmful agent. To corroborate what I report it is sufficient to perform the PCR assay immediately before and after vaccination. If my data is confirmed by that of the Department of Images, then a thorough reflection will be necessary, since the hippocampus intervenes in senile dementia, Alzheimer's Disease, the transformation of memory from short to long term, and in neuronal plasticity and in the mood. References 1) Sergio Stagnaro. Psychokinetic Diagnostics, Quantum Biophysica Semeiotics Evolution. http://sciphu.com/. 12 March 2010, http://sciphu.com/2010/03/psychokinetic-diagnostics-quantum.html and http://wwwshiphusemeioticscom-stagnaro.blogspot.com/2010/03/psychokinetic-diagnostics-quantum.html 2) Sergio Stagnaro. Psychokinetic Diagnosis and two Dimensions of Time, T1 and T2. http://www.sci-vox.com, 23 August, 2010. http://www.sci-vox.com/stories/submit.html 3) Sergio Stagnaro. PSYCHOKINETIC DIAGNOSTICS, QUANTUM-BIOPHYSICAL-SEMEIOTICS EVOLUTION. Journal of Quantum Biophysical Semeiotic Society. http://www.sisbq.org/uploads/5/6/8/7/5687930/psychokineticdiagnostics_qbsevolution.pdf 4) Sergio Stagnaro and Simone Caramel (2012) New ways in physical Diagnostics: Brain Sensor Bedside Evaluation. The Gandolfo's Sign. January, 2012. Journal of Quantum Biophysical Semeiotics. http://www.sisbq.org/uploads/5/6/8/7/5687930/bsbe.pdf 5) Sergio Stagnaro, Simone Caramel (2020). Un vaccino covid-19 a mRNA attiva i Brain Sensors del Sistema Limbico. http://www.sisbq.org/uploads/5/6/8/7/5687930/pfizerhippocampus.pdf Laureano MestraCo-founder, Mast Cell Research Institute.10 January 2021 A plausible approach for COVID-19 mass vaccination Sirs, I am pleased to read this article because from the global health perspective, if the access to a safe and effective vaccine is not wide enough, COVID-19 could turn into a poverty disease in the short term. The authors propose an interesting approach and, to reinforce it an analogy could be helpful. A couple of years ago, a couple of initiatives have evaluated the safety and efficacy of their dengue vaccine (1,2). Even though the efficacy results have not been as high as expected, the use of a vaccine with an efficacy above fifty percent could be good enough to reduce the burden of disease dramatically in areas with high transmission rates. Therefore, and also based on the model presented by the authors, a one dose regime to increase the coverage of a COVID-19 vaccination program is plausible. Especially if we one considers the expected capacity of the vaccine to block SARS-CoV-2 transmission. References 1. Biswal S, et al. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N Engl J Med. 2019. PMID: 31693803 Clinical Trial. 2. Villar L, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015. PMID: 25365753 Clinical Trial. Disclosures: I declare no to have any conflict of interest. Author, Article, and Disclosure InformationAuthors: A. David Paltiel, PhD; Amy Zheng, BA; Jason L. Schwartz, PhDAffiliations: Yale School of Public Health, New Haven, ConnecticutHarvard Medical School, Boston, MassachusettsFinancial Support: Dr. Paltiel was supported by grant R37DA015612 from the National Institute on Drug Abuse of the National Institutes of Health.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7866.Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: The underlying model that we adapted to produce these results is available in the appendix of reference 4.Corresponding Author: A. David Paltiel, PhD, Yale School of Public Health, 60 College Street, New Haven, CT 06510; e-mail, david.paltiel@yale.edu.This article was published at Annals.org on 5 January 2021. 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