Exploring Risks of Human Challenge Trials For COVID-19

Area of Science:

• Infectious Diseases
• Clinical Trial Design
• Risk Assessment

Background:

• Human challenge trials (HCTs) offer accelerated vaccine and therapeutic development.
• COVID-19 HCTs present unique ethical and safety challenges due to evolving risk understanding.
• Assessing severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) dosing study risks is crucial for HCTs.

Purpose of the Study:

• To introduce an interactive model for exploring risks associated with SARS-COV-2 dosing studies.
• To estimate individual and overall mortality and hospitalization risks for COVID-19 HCTs.
• To provide a web tool for evaluating risks across different study designs.

Main Methods:

• Utilized a Bayesian evidence synthesis model to estimate infection fatality risks (IFRs) and hospitalization rates.
• Incorporated new data on IFRs and inferred hospitalization rates.
• Extrapolated individual risk estimates to a dosing study population.

Main Results:

• Baseline IFR for 20-30 year olds estimated at 15.1/100,000 (95% UI: 11.8-19.2); hospitalization risk at 130/100,000 (100-160).
• With safety measures (screening, lower-risk population, treatment), projected fatality risk reduced to 2.5/100,000 (1.6-3.9); hospitalization risk to 22.0/100,000 (14.0-33.7).
• A 50-person dosing trial demonstrated a 99.74% chance of no fatalities and 98.9% probability of no hospitalizations.

Conclusions:

• The developed model and web tool facilitate risk assessment for COVID-19 HCTs.
• Safety protocols significantly mitigate risks in SARS-COV-2 dosing studies.
• COVID-19 HCTs, including dosing studies, can be conducted with acceptably low risk levels.