People ages 65 and older have the highest rate of chronic disease among any age group — nearly 95% have at least one chronic disease, such as heart disease, arthritis or diabetes, and about 80% have two or more. They are also the heaviest users of medication.
Despite this medical need, clinical trial enrollment of older adults remains low.
In the mid-1990s, fewer than 25% of participants in oncology trials were older adults, even though they made up roughly 67% of new cancer diagnoses and 75% of deaths. Participation in oncology trials among this age group now hovers around 30%, according to Sharmeen Roy, chief strategy and science officer at DoseMeRx, a Florida-based provider of precision drug dosing software.
That’s slowly changing, spurred by an FDA push to boost diversity in trials. The agency issued several guidance documents in recent years aimed at enrolling more adults over age 65, in addition to other underrepresented groups.
But the numbers still aren’t where they need to be, Roy said.
“I think it is improving, but there's room to grow and a lot more that needs to be done,” she said.
A critical demographic
There’s great interest in developing drugs for conditions that disproportionately affect older adults, and nearly 450 of these drugs are in clinical trials. There’s also an incentive to improve care — the cost of managing these diseases is high, making up two-thirds of all healthcare costs overall and 93% of Medicare spending, according to PhRMA.
Drugs often don’t work the same way in this age group as in younger people, Roy said. Older people may take longer to metabolize medications, increasing the risk of toxic reactions at doses that may be safe for someone younger. They may also be on medications that interact with the trial drug, Roy said, rendering many people ineligible.
“I personally had to set up a drive-through pharmacy for my research patients to pick up their medications so there were no missed doses and they could still continue with their visits."
Chief strategy and science officer, DoseMeRx
One blood pressure trial in very elderly adults, for example, looked to assess whether a blood pressure treatment could reduce stroke risk in people over age 80. However, less than 2% of identified patients met inclusion criteria.
While some trials bar older adults based on their health, other exclusions are based solely on age.
“A lot of these older patients get excluded even though they're healthy adults,” Roy said.
These inclusion barriers can limit information about how medications will perform in real-life users, who tend to be older and sicker than people in research studies.
“Oncology medications have a lot of adverse effects and toxicities, so we're not fully understanding how older patients may respond to these therapies and even what may be the appropriate dosing for these patients,” Roy said
The same is true for other types of medication as well. Making enrollment criteria more flexible can help ensure that more older adults are eligible to participate, Roy said.
Inclusion criteria aren’t the only barriers to trial participation. Many older adults simply don’t know that clinical trials are an option due to insufficient outreach, despite substantial interest in taking part. More than two-thirds of older adults said they would sign up for a trial if their doctor recommended it, but research has found that doctors are less likely to offer the clinical trial option to older patients.
Older adults may also need help navigating complex logistical hurdles that may otherwise dissuade them from participating. Many elderly people need assistance from a caretaker to get to the trial site, the lab or imaging appointments. Some sites provide or cover the cost of transportation or adopt a decentralized model, using virtual visits or other strategies to lessen the burden.
“I think that can be helpful if you’re doing outreach specifically for older adults and going to them and making it more convenient,” Roy said.
Clinical trials can be stressful for someone young but are more so for people who are older or in poor health.
“It's a lot for any patient to be in a clinical trial, so you have to almost customize an approach for the elderly population,” Roy said, adding that he had to try novel solutions to keep trials moving during the COVID-19 pandemic.
“I personally had to set up a drive-through pharmacy for my research patients to pick up their medications so there were no missed doses and they could still continue with their visits,” she said. “Sometimes you have to get creative and make sure that they have the resources available.”
Providing ongoing support to patients, particularly when they have burdensome health conditions, can keep people from dropping out.
Another challenge is informed consent. Those experiencing cognitive decline will need a proxy to sign informed consent forms, but weighing the pros and cons of a trial can be difficult even for those who don’t.
“I have served on a couple institutional review boards and part of the review process is reviewing the consent very closely and making sure that it's at a level where the patient can understand and it's not overwhelming,” Roy said. “That's the goal. You want to make sure they're fully understanding what they're signing up for. Because if they don't, often times you'll see you get the enrollment, they get started and then when they realize what is involved, they’ll drop out. We want to avoid that and make sure that it's truly an informed consent.”
This process should be cognizant of generational, cultural and language barriers.
“In South Florida we have a very diverse population, and we have those challenges and barriers to really understanding the benefits of clinical trials,” Roy said.
In addition to measures taken by sponsors, the push by the FDA will likely continue to increase participation among older adults. Pediatric patients also used to be underrepresented in clinical trials until the FDA pushed for inclusion.
“There were FDA guidance incentives to have those trials,” Roy said. “Now we're at the other end of the spectrum where we have an aging population.”
The country’s population of older adults is growing, so the time is right for change. Some 56 million Americans are over age 65, and that number is expected to climb to 80.8 million by 2040.