COVID-19 vaccine trial designs in the context of authorized COVID-19 vaccines and expanding global access: ethical considerations

Overview

Executive Summary

In June 2020, global regulators convened under the auspices of the International Coalition of Medicines Regulatory Authorities (ICMRA) and co-chaired jointly by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) reached consensus on the study design requirements for Phase 3 COVID-19 vaccine clinical trials. The ICMRA noted that phase 3 clinical trials should be randomized, double-blinded and controlled with a placebo or active comparators. In September 2020, the World Health Organization (WHO ) advised: “Phase IIB/III efficacy trials should be randomized, double-blinded and placebo controlled.” Since then, multiple COVID-19 vaccines have been authorized worldwide based on interim results of pivotal placebo-controlled efficacy trials, and billions of COVID-19 vaccine doses have been administered under emergency use/conditional marketing authorization or full approval regulatory mechanisms.

In December 2020, a WHO expert group advised that the placebo control arms of COVID-19 vaccine trials should be progressively unblinded as authorized vaccines become available in the community hosting the trial, starting with prioritized groups.

Before a COVID-19 vaccine trial commences enrolment, if one or more authorized/approved COVID-19 vaccine is locally available and the participant meets programmatic eligibility criteria, the study team should advise the participant that they are eligible to receive the authorized vaccine(s). Participants may elect to receive the authorized vaccine at any point in the trial.

The appropriateness of conducting a placebo control trial may depend on whether the candidate vaccine is a prototype vaccine, modified vaccine or next generation vaccine.

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Working Group on Ethics and COVID-19

Ethics and COVID-19