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Standing trial


Firming up the evidence base beneath Covid-19 vaccines

The Coalition for Epidemic Preparedness Innovations has played a pivotal role in funding global efforts to develop vaccines in very short timescales during the Covid-19 pandemic. Its funding helped push the accelerator pedal on successful vaccines developed by Moderna, Novavax and the University of Oxford and AstraZeneca.

Now, rather than directly supporting vaccine development programmes as it has previously done during the pandemic, Cepi has announced a wider call for Covid-19 clinical development work, open to any research group with the capacity to run clinical trials. The aim of the $140 million (€116m) call is to plug gaps in the evidence for Covid-19 vaccines, as long as they are either licensed or already in human trials.

Jakob Cramer, head of clinical development at Cepi, says that the focus in 2020 was on rapidly supporting vaccine development but that it’s now important to broaden the evidence base.

“There are obviously a lot of additional questions that come up that are not on that straightforward pathway to licensure,” Cramer says, adding that many of those questions have become more important now that we know the virus will be with us for a while yet. “The aim for this particular call is really to fill in some of these gaps.”

Not only are the vaccines being rolled out the first to be used against a coronavirus, but many involve technologies that have not previously been used in any licensed vaccine, Cramer points out. “So there are a lot of clinical development gaps and a lot of information that needs to be generated,” he says. As a result, the call is focused both on this pandemic and on helping to “understand and build trust in these new platform technologies”.

Expanding access

Several of the knowledge gaps that relate to vaccine safety and efficacy are in groups that have not been well represented in trials so far. “We know that pregnancy, for example, is a risk factor for severe disease, and no clinical trial has been performed in pregnant or lactating women yet,” Cramer says. “So this is certainly one focus.”

Furthermore, vaccine rollout has been concentrated on vulnerable and older age groups, but frail or older adults living in nursing homes have not been well represented in large, phase three trials for assessing vaccine efficacy. This evidence gap has been the cause of some controversy, particularly with the Oxford-AstraZeneca vaccine, with Germany and France deciding not to offer the vaccine to those over the age of 65, even though other countries, including the UK, are. And while some trials have included 16-and-17-year-olds, none have included younger age groups, Cramer adds.

Cepi also welcomes proposals in other areas where the evidence is thin, such as understanding more about the immune response triggered by a vaccine, or assessing whether vaccines are effective against the variants that are causing major concern around the world. Cramer says the call “allows us to react in a very flexible manner” based on what happens as the pandemic continues to unfold.

Cepi is a leading member of Covax, a global initiative aiming for equal access to Covid-19 vaccines. In a statement on the new variants, Covax said that research funded under Cepi’s call could include “mix-and-match studies” of different vaccines to optimise their use.

The call is open to research groups in any country, as long as they have access to a vaccine. “One very important aspect, in particular for us at Cepi, is to encourage clinical trials in low-income and middle-income countries,” Cramer says, especially given most trials have been in higher-income countries. All applicants must state how their proposal can support access to affordable vaccines in low-income and middle-income countries, in particular through the Covax initiative.

While proposals for vaccines still in development would have to involve the developer, trials of already licensed vaccines can be run independently. There is no upper limit on funding for projects, but Cramer points out that the aim is not to support large, costly, phase three clinical trials. Nor can the call support research on biological therapies or first-in-human vaccine trials. “It has to be a vaccine, it has to be a clinical trial and it has to be a project that is already in the clinic,” he summarises.

Quick turnaround

As it has been throughout the pandemic, time is of the essence. Cramer says that the ability to get trials up and running quickly is a prerequisite, with one of the review criteria for proposals being the ability to generate an interim analysis of data from any trial by the end of the year. “The earlier the better,” he urges.

The deadline for proposals is 28 May, but Cramer says the call could close early or be extended, depending on the applications received and how the pandemic plays out in the weeks ahead.

To stimulate early submissions, Cepi will review proposals on a rolling basis. “We know if you set a deadline, most applications come in within a week, or even a few days, before the deadline,” Cramer says. “We are prepared to contract in a very fast way…if applications come in that address relevant questions.”  

This is an extract from an article in Research Professional’s Funding Insight service. To subscribe contact sales@researchresearch.com