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 article , we introduce an interactive model for exploring some risks of a severe acute respiratory syndrome coronavirus‐2 (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 risks (IFRs) to patients, and infer rates of hospitalization. The model estimates individual risk, which we then extrapolate to overall mortality and hospitalization risk in a dosing study. We provide a web tool to explore risk under different study designs. Based on the Bayesian model, IFR for someone between 20 and 30 years of age is 15.1 in 100,000, with a 95% uncertainty interval from 11.8 to 19.2, while risk of hospitalization is 130 per 100,000 (100–160). However, risk will be reduced in an HCT via screening for comorbidities, selecting lower‐risk population, and providing treatment. Accounting for this with stronger assumptions, we project the fatality risk to be as low as 2.5 per 100,000 (1.6–3.9) and the hospitalization risk to be 22.0 per 100,000 (14.0–33.7). We therefore find a 50‐person dosing trial has a 99.74% (99.8–99.9%) chance of no fatalities, and a 98.9% (98.3–99.3%) probability of no cases requiring hospitalization.

Research ethics and public trust in vaccines: the case of COVID-19 challenge trials

“… 8 All HCT volunteers are young and healthy, a population in whom the chance of severe COVID-19 outcomes is small. 9 All remain isolated while infectious.…”

“…But HCTs’ danger to public trust that follows serious adverse events may be smaller than that of widely accepted conventional field trials. Properly conducted HCTs’ extremely low chance of serious adverse events 9 may actually be smaller than the risk of serious adverse events (including ones stemming from trialists’ active interventions) in properly conducted field trials. The latter expose hundreds of times more participants to the vaccine (greatly elevating the risk of vaccine toxicity events) and many more people to the combination of vaccine and virus (elevating risk of disease enhancement events 51 —especially given that many participants could get exposed to the virus shortly after the trial).…”

A new day for human challenge trials?

“…Challenge trials are safer for volunteers now that effective treatments have now been rigorously tested. Pfizer’s Paxlovid reduces the risk of COVID-19-related hospital admission or death by 89%, bringing down the already low risk of severe illness for young, healthy challenge by an order of magnitude, though long COVID effects remain somewhat unclear [ 6 ]. Finally, regulators in the US, UK, and Europe have agreed to rely simply on the immune response triggered by vaccines for some purposes, for example, for testing targeted vaccines.…”

The third ethical commentary to COVID-19 (two years later) — vaccination, solidarity, and trust

“…Что касается научно-технологического подхода, то при создании специфических вакцин были использованы стратегии, выработанные в отношении других исследовательских практик, что исключало наличие адекватного экспериментального ресурса [5]. Беспрецедентной также можно назвать ситуацию невиданного [86,89,92,96,97]. В рамках данного обзора важно привести результаты нашего анализа этического аспекта таких подходов [30].…”