Ongoing and future COVID-19 vaccine clinical trials: challenges and opportunities

Abstract

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebocontrolled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resourcepoor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, noninferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

Unveiling Associations of COVID-19 Vaccine Acceptance, Hesitancy, and Resistance: A Cross-Sectional Community-Based Adult Survey

“…COVID-19 vaccines are considered to be a key to attain herd immunity and flatten the current epidemic curve. However, concern about vaccine hesitancy was growing worldwide, even before the COVID-19 pandemic outbreak, prompting the World Health Organization (WHO) to declare it among the top 10 health threats in 2019 [ 11 ]. The success of the COVID-19 vaccination program will rely on the rates of vaccine acceptance among the population, but several determinants influence whether an individual refuses, delays, or accepts some vaccines.…”

“…The minimum standard time to develop a vaccine is estimated to be between 1–1.5 years, as different steps are necessary during the clinical development. Among these steps, recruitment of volunteers in a vaccine clinical trial is a real challenge, and sometimes, some trials must be stopped due to difficulties in recruitment [ 10 , 11 ]. After its clinical development, a vaccine also faces the challenge of acceptance by the general population.…”

Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

“…In clinical trials, the Jansen vaccine has been tested against a variety of SARS-CoV-2 virus variants, including B1.351 (first identified in South Africa) and P.2 (first identified in Brazil), and found to be effective. Good results have also been found for the Pfizer vaccine [71,72].…”

Placebo control group in COVID-19 vaccine trials: context and timing matters

“…Today, regrettably, hundreds of millions of individuals that live in low- and middle-income countries lack access to temporarily authorized COVID-19 vaccines due to limited vaccine availability and will do so well into 2023 [ 7 ]. However, in these territories, and until sufficient knowledge on immunogenicity, safety and efficacy of multiple COVID-19 vaccines is gathered, especially with the widespread of different SARS-CoV-2 variants of concern, double-blind placebo-controlled trials can and should be considered in the clinical development of new COVID-19 vaccine candidates [ 8 – 10 ]. In these trials, participants should only be included with fully informed consent and the best possible standard of COVID-19 care must be available to all participants.…”

“…Participants should be allowed to unblind and access a known effective vaccine should one become available to them. In addition, and in particular, the research should respond to local needs (placebo-controlled trials should be done in regions impacted with high burden of COVID-19), both participants and communities should benefit from the trial, and the vaccine candidate to be tested, if proved to be efficacious and safe, should be made available in the country where the trial is conducted [ 8 ]. To this end and from the very beginning, transparency should be the fundamental guiding principle in the cooperation between the sponsor and local stakeholders with full community partnership and engagement throughout.…”