Exploring Risks of Human Challenge Trials for COVID-19

Abstract

Human Challenge Trials (HCTs) are a potential method to accelerate development of vaccines and therapeutics. However, HCTs for COVID-19 pose ethical and practical challenges, in part due to the unclear and developing risks. In this paper, we introduce an interactive model for exploring some risks of a SARS-COV-2 dosing study, a prerequisite for any COVID-19 challenge trials. The risk estimates we use are based on a Bayesian evidence synthesis model which can incorporate new data on infection fatality rates (IFRs) to patients, and infer rates of hospitalization. We have also created a web tool to explore risk under different study design parameters and participant scenarios. Finally, we use our model to estimate individual risk, as well as the overall mortality and hospitalization risk in a dosing study.Based on the Bayesian model we expect IFR for someone between 20 and 30 years of age to be 17.5 in 100,000, with 95% uncertainty interval from 12.8 to 23.6. Using this estimate, we find that a simple 50-person dosing trial using younger individuals has a 99.1% (95% CI: 98.8% to 99.4%) probability of no fatalities, and a 92.8% (95% CI: 90.3% to 94.6%) probability of no cases requiring hospitalization. However, this IFR will be reduced in an HCT via screening for comorbidities, as well as providing medical care and aggressive treatment for any cases which occur, so that with stronger assumptions, we project the risk to be as low as 3.1 per 100,000, with a 99.85% (95% CI: 99.7% to 99.9%) chance of no fatalities, and a 98.7% (95% CI: 97.4% to 99.3%) probability of no cases requiring hospitalization.

Global Systemic Risk and Resilience for Novel Coronavirus and COVID‐19

“…While human dosing trials are the gold standard for producing suitable data for dose-response modeling, ethical challenges often limit the ability to conduct such studies especially for highly infectious agents. Manheim et al (2020) introduce an interactive model for exploring risks of severe outcomes in human cohorts from participating in SARS-COV-2 dosing study, a prerequisite for any COVID-19 challenge trials. The risk estimates they generate are based on a Bayesian evidence synthesis model, which can incorporate new data on infection fatality risks (IFRs) to patients, and infer rates of hospitalization.…”

“…Manheim et al. (2020) introduce an interactive model for exploring risks of severe outcomes in human cohorts from participating in SARS‐COV‐2 dosing study, a prerequisite for any COVID‐19 challenge trials. The risk estimates they generate are based on a Bayesian evidence synthesis model, which can incorporate new data on infection fatality risks (IFRs) to patients, and infer rates of hospitalization.…”

COVID-19 controlled human infection studies: worries about local community impact and demands for local engagement

“…For their own safety, in a typical SARS-CoV-2 CHI, participants would all be young and healthy, a population in whom the chance of adverse COVID-19 outcomes or hospitalisation is small. 2 …”

“…It was recently calculated that in a 50-person CHI, the chance of having simply no hospitalisation is 98.4%. 2 30 The chance that not a single intensive care bed would be occupied should be even higher.…”

Do coronavirus vaccine challenge trials have a distinctive generalisability problem?

“…1 3 4 6-8 But in all SARS-CoV-2 HCT plans, the key volunteer protection is recruiting only young adults who are free from major risk factors for severe COVID-19 following infection. 1 3 4 6-8 That exclusionary criterion alone is estimated to reduce the risk of fatality from the HCT (or the viral dose escalation study) to around 3 in 100 000, 9 which is about 100th the risk of perioperative death from live right liver lobe donation. [10][11][12] Since participation could and should be conditioned on high-quality informed consent, recruitment would be permissible, just like recruitment of live kidney donors.…”