This was the eleventh meet-up co-sponsored by NISS and Merck and the first of 2021. The last meet-up in September of 2020 broached the same topic of how vaccines are developed with some emphasis on the current pandemic, but so much has changed since then. Now that a few vaccines have become available, this meet-up was able to focus a little deeper into study design for vaccines to SARS-COV-2 considering general efficacy trial design and some thoughts for measuring response, looking at some of the largest current studies to see how some of these considerations are playing out in practice.
Once again, moderator Dan Holder (Merck) brought together three experts to talk about the very latest issues in vaccine development.
The first speaker was Natalie Dean from the University of Florida. Natalie provided a thorough introduction to vaccine efficacy trials, the general expectations of vaccine development, the regulatory pathway in place and how this pathway was accelerated because of the pandemic. She then moved on to describe the varying vaccine platforms, the current status of those vaccines that are in process and unique features of current COVID-19 trials.
“The principal goal of a vaccine efficacy trial is to obtain efficacy and effectiveness data that can support broader use of a vaccine under a defined regulatory framework.”
Natalie Dean (University of Florida)
Kert Viele (Berry Consultants) took things a bit deeper by focusing his remarks on the interim analyses, i.e., now that we know what happened in a couple of trials … what did we learn? He began by reviewing the four trials that have taken place to date: AstraZeneca, Janssen, Moderna and Pfizer. Kert first talked in general about the importance of sample size and safety (both short-term, long-term and disease severity), but then got down to the details involved in interim analyses. Essentially, his remarks focused on how determination is initially reached regarding the efficacy of a vaccine, i.e., How can we be certain that the vaccine is producing the results that we want it to prior to any kind of long term follow up?
The final speaker was Jonathan Hartzel (Merck). Continuing where Kert left off, Jonathan discussed the issues surrounding where we need to go from this point. After establishing how important it is that vaccine development research continue, he discussed issues that will have to be contended with by those scientists involved in future efficacy trials. The most important issue is the role of blinded, placebo-controlled trial designs once vaccine becomes available and the ethical questions associated with this. Jonathan suggested that this might lead to deferred or delayed vaccination trials. In addition, he also discussed active controlled efficacy trials (non-inferiority) as a further alternative and described what these types of trial designs would involve.
Once again, the audience at the NISS-Merck meet-ups were certainly forthcoming with their questions and comments for the speakers to discuss! But first moderator Dan Holder (Merck) prodded the panelists to ask each other questions which started a lively discussion among panelists before addressing the questions from attendees. The energy in the room continued around questions such as: “When we compare the efficacy of different vaccines what is the best way to compare them? Then further, can we combine these comparisons into some sort of score?” And, “What is the right efficacy measure to use?” Another interesting issue that the panelist commented regarding the introduction of bias. For instance: “An individual can go get an antibody test to see if the were in the placebo group. How are behaviors like this and others handled?” On another topic, “Having been developed so quickly, are there any compromises with regarding safety? In what area might we be lacking the most from these programs compared to the longer trials that have occurred in the past?” The questions quickly got to the heart of the issues being discussed, and the responses and back and forth between the panelists underscored their understanding of current developments and the importance of this research.
Recording of the Session and Slides Used by the Speakers
Slides Used by the Speakers
Natalie Dean, (University of Florida)
Kery Viele, (Berry Consultants)
Jonathan Hartzel, (Merck)