Can older adult clinical trial participation be boosted?

Regulatory NewsRegulatory News | 25 March 2021 |  By 

The US Food and Drug Administration on Tuesday convened leaders from the agency, industry and academia to tackle barriers and solutions to enrolling older adults in clinical trials. Highlights of the virtual public workshop included solid data from FDA showing the mismatch between disease prevalence and age representation in clinical trials, as well as an in-depth examination of how older adults were represented in COVID-19 vaccine trials.
S. W. Johnny Lau, PhD, a senior clinical pharmacologist in the Office of Clinical Pharmacology at FDA, made the point that in many conditions common in the elderly, clinical trial participation is weighted to younger age groups, while prevalence holds steady or climbs with increasing age.
Pointing to a chart that mapped clinical trial participation by age against the prevalence of non-small cell lung cancer (NSCLC), Lau said, “This graph shows a double whammy because the percentage of clinical trial population dropped towards the older population, whereas the prevalence of non-small cell lung cancer increases in this population.”
The findings were drawn from an FDA-led study that looked at six therapeutic indications common in older adults. Lau and his collaborators searched internal clinical trial data submitted in support of new drug approvals (NDAs) or biological license applications (BLAs) between 2010 and 2019 and compared participation rates with prevalence data for community-living older adults drawn from publicly available databases and the published literature. Similar trends to those found for NSCLC were seen, especially for patients aged 80 years and up, for such indications as heart failure, insomnia, osteoporosis, and prevention of stroke associated with non-valvular atrial fibrillation.

Harvard’s Sharon Inouye, MD, MPH, reviewed findings published in a Sept 2020 JAMA Internal Medicine Clinical Research Letter. The letter, for which Inouye was the senior author, detailed a variety of ways in which older adults were excluded from COVID-19 clinical trials.
In addition to exclusion by age, Inouye and her colleagues found that many other exclusions based on compliance and consent concerns, comorbidities or medication use indirectly excluded older adults.
Of 18 phase 3 vaccine clinical trials examined by the investigators, 11 had age cut-offs. Seven additional trials had “broad non-specified exclusions” with the potential to exclude older adults; all of the trials were thus “considered high risk for excluding older adults.”
Anecdotally, said Inouye, people were excluded for seemingly trivial reasons. “People contacted me saying, you know, ‘I have hypertension; I’m only on one medication, and they excluded me from the study.’” She also heard from an individual with a remote history of long-cured breast cancer. “And so, I have many, many stories like that and so the ear is that many of these may have been really healthy” potential participants, she said.
After she and her colleagues sounded the alarm, they took a look at published studies of four vaccines. Though there was variable inclusion of older adults and those with comorbidities, not one trial included participants who lived in nursing homes. “To assure applicability and relevance of clinical trials results, we must find ways to include the older population in adequate representation with which they are affected by the disease in question.”
What are some solutions? Inouye had ample solutions to consider for a wide spectrum of enrollment challenges for older adults. Hearing and vision impairment can be overcome with assistive devices and better staff training, for example. Mobility impairments can be addressed similarly.
“Do not exclude for chronic, stable comorbidities of mild degree,” she said. Exclusions should be justified and only arrived at after geriatricians are consulted.
Ethical alternatives exist to allow individuals with mild cognitive impairment or memory issues; these include adequate assessment for capacity to consent and willingness to enlist proxies when needed.
“I do this for a living, and it is very doable to enroll older adults in large numbers in clinical trials,” Inouye said. “I guarantee you that where there’s a will there’s a way.”


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