Global regulators promote platform trials to assess new COVID vaccines
Regulators from the United Kingdom and Japan are promoting the use of platform trials to evaluate second-generation COVID-19 vaccines as the pool of unvaccinated patients for testing new vaccines grows increasingly smaller. They also proposed the creation of a working group to build consensus on the design of master protocols, particularly in the context of health emergencies.These pronouncements emerged from a 24 June virtual workshop on aligning approaches for developing second-generation COVID-19 vaccines and boosters sponsored by the International Council of Medicines Regulatory Authorities (ICMRA). The workshop was attended by delegates from over 20 countries and delegates from the World Health Organization.
At the workshop, regulators from the Japanese Medical Devices Agency (PMDA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) proposed increased use of “platform” study designs, or using several investigational drugs with a single active comparator to evaluate vaccine efficacy, as a “suitable” alternative to conventional clinical trials for COVID-19 vaccines.
FDA acting commissioner Janet Woodcock has long been a proponent of master protocols, citing their ability to evaluate multiple agents efficiently once they’re up and running. (RELATED: DIA: Woodcock, other top officials tout benefits of maser protocols, want momentum to continue post-COVID, Regulatory Focus 2 July 2021).
Finding alternative study designs for COVID-19 vaccines is a critical need, as it is getting increasingly difficult to conduct traditional placebo-controlled studies as more people are vaccinated, noted attendees.
Non-inferiority trial designs may help overcome some of these challenges, but “there remain open questions including selection of active comparators, levels of correlates of protection and immunogenicity, clinical endpoints (and objectives, such as prevention of serious disease or of transmission),” according to the report from the workshop. The appropriate period of follow-up to track duration of vaccine protection also remains an open question.
Attendees proposed the creation of an ICMRA Clinical Trials Working Group that to “promote international trials and to build consensus among regulators on master protocols and designs, particularly in the context of health emergencies."
At a brainstorming session, there was agreement that regulators need to reach alignment on “appropriate” study designs to demonstrate the effectiveness of second-generation COVID-19 vaccines; workshop attendees also cited the need to generate robust data for authorization. Approaches to authorizing second-generation vaccines may include placebo controlled clinical disease endpoint trials, if such trials can be performed ethically. Other approaches could include relative clinical disease endpoint efficacy studies or, potentially, even human challenge trials.
There was consensus that immunogenicity bridging studies may be needed for assessing effectiveness of second-generations COVID-19 vaccines if clinical endpoint efficacy studies are no longer feasible.
In addition, those in attendance agreed that selecting immune markers to predict effectiveness and using population comparator groups matched by age, gender and prior vaccination status are “critical factors to agree on.”
ICMRA will conduct another workshop in the fall that will focus specifically on second-generation vaccines.
ICMRA meeting minutes
