Vaccine experts urge more inclusivity in clinical trials

The recently approved RSV vaccines have been celebrated as key public health tools, but some vaccine experts have lamented one aspect of the trials that led to their approval — namely, that older adults were largely left out of them.

Among adults, RSV poses the biggest threat to the oldest seniors and people with certain preexisting health conditions. But the trials for the vaccines, which have been approved for adults 60 and older, included few participants 80 and older. People who are immunocompromised and those who live in nursing homes were also not included.

“Yeah, it works great in a healthy 60-year-old, but how does it work in the general population?” Helen “Keipp” Talbot, a geriatric infectious diseases specialist from Vanderbilt University, said at the STAT Future Summit on Tuesday. “The population that we’re intending to use the vaccine in, how well does it work? What can we anticipate? What’s the cost-effectiveness of the vaccine?”

Talbot and fellow vaccine expert Ruth Karron of the Johns Hopkins Bloomberg School of Public Health spoke on a panel about some of the challenges involving vaccine trials and how they could be improved. They noted that some vaccine trials don’t include the oldest adults even when they’re the target demographic for the vaccine being tested.

It makes sense that researchers start by enrolling healthy adults in the first human trials for vaccine candidates, Karron explained. If there are unexpected safety issues, the risk to healthy adults is likely to be lower than to frail older adults.

But as vaccines move into larger efficacy studies, Karron said, “I think the question is not so much about starting in that age group as perhaps, where do we go from there?”

It’s important to study vaccines in older adults and people with health conditions not just because they’ll be the key recipients of many immunizations, Talbot argued. As we age, our immune systems age as well, and they often can’t mount as robust responses to vaccines as younger immune systems.

“So we enroll those 60-year-olds who are healthy and then try to extrapolate” the results, Talbot said. “But it’s unclear how well that extrapolates.”

Helen Branswell, STAT’s senior writer for infectious diseases and the moderator of the panel, asked whether the Food and Drug Administration should require vaccine manufacturers to enroll frail adults or those who live in settings like nursing homes in trials, akin to how regulators required Covid-19 vaccine trials to include diverse participant groups.

Karron and Talbot both acknowledged that focusing on healthy adults has its advantages. Enrolling frail people, some of whom can’t drive to appointments, would require more work — making trials longer and costlier, for example. That population is also more likely to have strokes or be hospitalized for any number of reasons — and investigators would have a harder task sorting through which health issues are incidental and which are potential side effects tied to a vaccine.

Karron also raised the hypothetical question of whether a requirement to include a certain number of people in congregate living settings could cause a delay in the approval of a vaccine — say, by two years. “There would be older adults potentially deprived of that vaccine in that two-year period who could become seriously ill with a pathogen against which you’re developing the vaccine,” she said.

But both experts also suggested there are ways to make enrollment in vaccine trials more inclusive.

Talbot noted that the Covid-19 pandemic and the record-setting development of those shots may be influencing expectations of how long it typically takes to gather vaccine data.

“I think we have forgotten how to slow down a bit. We’re still in that hurry mode,” Talbot said about coming out of Covid.

“We really wanted the RSV vaccine because we see unnecessary death and morbidity and mortality — that was something that pushed us fast,” she continued. “But in years past, we may have been able to slow down a little bit and say, wait a minute, we don’t have to go Warp Speed for everything.”