We, (ICMRA members, a global coalition of medicine regulators) have an important role in supporting the worldwide effort to ensure the quality, safety and efficacy of licensed vaccines and to make them available to the public. We have stepped up our global collaboration to facilitate and expedite the development and evaluation of vaccines against SARS-CoV2 (causing COVID-19 disease).
This statement in support of continuing COVID-19 vaccine trials to collect critical data to support regulatory actions and deployment, for as long as is feasible, is intended for all stakeholders, vaccinees, researchers and investigators, academia, regulators and the pharmaceutical industry.
The pandemic represents a major global unsolved public health and economic crisis, which is still far from being under control as we see peaks of transmission, morbidity and mortality over time in different locations. The availability of safe and effective vaccines is anticipated to be an important component of the overall response to the emergency and to contribute to a return to normality.
Regulators have set up flexible and agile procedures to facilitate the swift analysis of clinical trial results submitted to them. These analyses will support clear, independent and transparent benefit-risk evaluations, leading to decisions on the approval of, or early access to, safe and effective vaccines against COVID-19.
To determine that the benefit of a vaccine outweighs its potential risk, regulators need robust and convincing evidence of the safety and efficacy that is obtained from well-designed randomised and controlled trials. Initial positive evidence of the vaccine’s safety and efficacy used to support a regulatory action may be based on planned interim or final analyses that occur when a pre-defined number of cases of COVID-19 disease have occurred in a clinical trial. In these situations, it will be of the utmost importance to continue gathering data about the vaccine safety and efficacy in the longer-term after the interim or final analysis is completed.
Specifically, continued follow-up of clinical trial participants after a regulatory decision has been made can provide important additional and more precise information on longer-term safety and efficacy against specific aspects of SARS-CoV-2 disease or infection, including efficacy against severe disease, efficacy in important subgroups, potential risks of vaccine-induced enhanced disease and whether protection against COVID-19 disease wanes over time.
Thus, continued evaluation of the vaccinated and the unvaccinated (control subjects who do not receive a vaccine against COVID-19) groups in clinical trials for as long as feasible will provide invaluable information.
For these reasons, investigators and sponsors should develop strategies to ensure continuation of follow-up of vaccinated and control groups for as long as possible after any regulatory approval that is based on planned analyses conducted while trials are still ongoing and after final analyses are completed.
Therefore, unless maintaining participants in their randomised treatment groups (vaccinated or control) after a vaccine is approved is clearly infeasible, we recommend that clinical trials should proceed as initially planned with a follow-up of at least one year or more from completion of assigned doses. In making this recommendation, we recognise that the feasibility of maintaining the group assignment for at least one year will depend on factors such as the population enrolled into a trial (e.g. in terms of whether they are young and healthy or have reasons to be predisposed to develop severe COVID-19), informed decisions made by clinical trial participants, the availability of COVID-19 vaccine(s), and the characteristics of SARS-CoV-2 epidemics. It will be necessary for sponsors, investigators, public health authorities and regulators to assess each situation that may arise.