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COVID-19:vaccines & therapeuticsData Science Zoomposium
Natalie Dean
Department of Biostatistics
University of Florida
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VA C C I N E S
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V A C C I N E S
COVID-19 vaccine platforms
Over 50 vaccine candidates currently in development, utilizing a range of vaccine platforms
Single
dose
Licensed
platform
Fast to
develop
RNA ✔✔
DNA ✔✔
Non replicating vector ✔ ✔
Inactivated ✔ ✔
Live attenuated ✔ ✔
Replicating viral vector ✔ ✔ ✔
Protein subunit ✔ ✔
Modified from Lurie et al. 2020 (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMp2005630
Table: Summary of general attributes
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V A C C I N E S
Typical regulatory pathway for vaccines
Preclinical data
Evidence of safety and anti-disease activity in animals
Requires a validated animal model
Phase 1 trials
First-in-human trials, focus on safety
Establish dosing
Phase 2a trials
Larger trials
Data on immunogenicity
Phase 2b/3 trials
Largest trials
Disease-related primary outcome (e.g. prevent COVID-19)
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V A C C I N E S
Accelerated regulatory pathway for vaccines
From Lurie et al. 2020 (NEJM) https://www.nejm.org/doi/full/10.1056/NEJMp2005630. Orange boxes my own.
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V A C C I N E S
COVID-19 vaccine landscape (March 26, 2020)
https://www.who.int/blueprint/priority-diseases/key-action/Novel_Coronavirus_Landscape_nCoV_Mar26.PDF.
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V A C C I N E S
What to look out for with vaccines?
Pay close attention to potential enhanced disease
Enrollment may be strategically targeted
Health-care workers, elder-care workers
Event-based monitoring
Duration of the trial will depend on smart placement of the study sites
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V A C C I N E S
Vaccine study site enrollment
Case-based surveillance
Serosurveys!
Spatially resolved models to integrate the two
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V A C C I N E S
Vaccine study site enrollment
Case-based surveillance
Serosurveys!
Spatially resolved models to integrate the two
Zhang et al. 2017 PNAS
https://doi.org/10.1073/pnas.1620161114
R0 for Zika by season
& location per the
GLEAM model
Unpublished modeling to guide
Zika vaccine site selection
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T H E R A P E U T I C S
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T H E R A P E U T I C S
COVID-19 candidate therapeutics
(a partial list)
Chloroquine, hydroxychloroquine
Antimalarial, safe, widely available**
Lopinavir/ritonavir
Protease inhibitor licensed for HIV
Can be provided with interferon-beta
Remdesivir
Unlicensed broad-spectrum antiviral
Favipiravir
Antiviral licensed for influenza in Japan
Tocilizumab, sarilumab, etc.
Antibodies licensed for arthritis
Could prevent an over-reactive inflammatory
response in the lungs
Convalescent plasma
Accepting donations now!
Manufactured antibodies
In development
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T H E R A P E U T I C S
COVID-19 candidate therapeutics
(a partial list)
Chloroquine, hydroxychloroquine
Antimalarial, safe, widely available**
Lopinavir/ritonavir
Protease inhibitor licensed for HIV
Can be provided with interferon-beta
Remdesivir
Unlicensed broad-spectrum antiviral
Favipiravir
Antiviral licensed for influenza in Japan
Tocilizumab, sarilumab, etc.
Antibodies licensed for arthritis
Could prevent an over-reactive inflammatory
response in the lungs
Convalescent plasma
Accepting donations now!
Manufactured antibodies
In development
Currently there are no licensed therapeutics
available for the treatment of COVID-19!
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T H E R A P E U T I C S
Tips on interpreting therapeutic study results
In vitro activity does not often translate into clinical benefit
Randomization is crucial
Therapeutics are typically only MILDY or MODERATELY effective
Expected outcomes (e.g. mortality) depend heavily upon the population studied
Pay attention to the sample size → Absence of evidence is not evidence of
absence
Similarly, pay attention to the trial population
Antivirals are most effective when provided early in the course of illness
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T H E R A P E U T I C S
Pre- and Post-Exposure Prophylaxis
Pre-exposure prophylaxis
Example: Healthcare workers
Post-exposure prophylaxis
Example: Household contacts
Early treatment
Example: Recent symptom onset
Target enrollment for a post-exposure prophlyaxis
and early treatment trial (http://www.trialcovid.com)
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G E N E R A L P R I N C I P L E S
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G E N E R A L P R I N C I P L E S
TRIALS, TRIALS, AND MORE TRIALS
https://www.nature.com/articles/d41586-020-00444-3
https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/
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G E N E R A L P R I N C I P L E S
Our recommendations (out today!)
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G E N E R A L P R I N C I P L E S
Guiding principles for clinical trial design
Avoid the publication of inconclusive results
Inconclusive results occur when studies are underpowered
Inconclusive results can jeopardize our ability to ever establish efficacy
One big trial is better than many small trials
Working together, we are best equipped to rapidly achieve answers
Have a plan in place at the start of the trial
Plan to expand to different locations
Plan to extend protocol into subsequent outbreaks
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G E N E R A L P R I N C I P L E S
Guiding principles for clinical trial design
Avoid the publication of inconclusive results
Inconclusive results occur when studies are underpowered
Inconclusive results can jeopardize our ability to ever establish efficacy
One big trial is better than many small trials
Working together, we are best equipped to rapidly achieve answers
Have a plan in place at the start of the trial
Plan to expand to different locations
Plan to extend protocol into subsequent outbreaks
https://www.sciencemag.org/news/2020/03/who-launches-global-
megatrial-four-most-promising-coronavirus-treatments
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T H A N K Y O U !
N a t a l i e D e a nn a t a l i e d e a n @ u f l . e d u
This work is supported by
NIH/NIAID R01-AI139761