Older adults are projected to outnumber kids for the first time in US history by 2034. As our population ages, preparations must be made across industries, fields of study and governments to address its evolving needs, including in clinical trials that set the standards for efficacy and safety of new treatments, especially in cancer. Ageism is an often-overlooked health inequity widely prevalent in cancer clinical research. Despite the fact that cancer is a disease of aging (42% of people with cancer are at least 70 years old), studies show that older patients comprise only 24% of participants in cancer trials.
Equitable representation in trials improves our understanding of a drug’s benefit-risk profile for patients who will ultimately receive treatment. This is especially true for cancer drugs, because differences may exist between younger and older adult patients in drug response and toxicity due to age-related physiological changes. Today, almost everything we know about cancer therapeutics is based on trials conducted in younger patients, who also have fewer functional or cognitive impairments and/or co-morbidities than older patients.
Recognizing the urgency of addressing this issue, the US Food and Drug Administration (FDA) issued new guidance in March 2022 that recommended “including an adequate representation of older adults in cancer clinical trials.” It also emphasized “the particular importance of including adults over the age of 75,” who represent a growing segment of the cancer patient population and a growing proportion of the global population.
The roots of this problem are deeply embedded in the systemic clinical trial infrastructure, regulatory requirements, and standard practices, all of which will need to be overhauled in the coming years as the population ages. In the meantime, those of us involved in cancer drug development, research, treatment, patient care and advocacy should evaluate which structural barriers can be navigated around to increase participation of older patients in clinical trials at present. Here are four actions we can take now:
Educate and engage patients and referring providers
According to the National Institutes of Health, a principal challenge of recruiting participants is the lack of awareness and education about clinical trials, availability and how to participate. In a nationwide survey, 80% of patients with cancer did not consider the possibility of participating in a treatment clinical trial because they were unaware that this was an option. This lack of awareness is anticipated to exacerbate in older adults as use of digital technology pervades clinical research and recruitment.
The cancer community must step up its efforts to educate and engage patients, site coordinators, patient advocates and caregivers about clinical trial protocols and participation. Educating referring physicians is an especially important, yet overlooked, way to increase enrollment of older adults in cancer clinical trials, as studies have shown that lack of primary care provider support is a key deterrent to clinical trial participation.
Re-evaluate eligibility criteria
The protocols for many cancer trials explicitly exclude a significant portion of older and frail adults because of their medical histories and co-morbidities. In a recent systemic review, researchers identified stringent eligibility criteria as a major barrier to older adults accessing available trials.
Eligibility criteria should be re-evaluated to ensure the reason for excluding these patients is based on strong clinical or scientific evidence. When creating these criteria, researchers should consider how they align with the physical and cognitive capabilities and medical conditions of those most likely to take the approved drugs. According to the new FDA guidance, trial sponsors should consider getting input on trial design, trial conduct and recruitment strategies from geriatricians, geriatric oncologists, and social and behavioral scientists. A study on barriers to participation recommended that “Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity and previous cancers.”
Bring research to the trial participants
Even when older patients do meet enrollment criteria, many do not want to participate in clinical trials because of transportation issues, time demands, and cost constraints. An obvious solution emerged during the Covid-19 pandemic – using technology to bring healthcare to the patient. “Telehealth” has become a new norm and the popularity of decentralized clinical trials skyrocketed after Covid-19.
The FDA Oncology Center of Excellence (OCE) supports the decentralization of clinical trials through the remote collection of trial data outside of standard in-person trial sites. Such methods can include: electronic informed consent, delivery of investigational product to the home, virtual clinic visits in patients’ homes for monitoring and data collection, and obtaining laboratory or imaging assessments locally. Decentralizing burdensome aspects of trials will remove obstacles to patient enrollment and participation, while providing healthcare providers with real-time data.
Design trials that focus solely on geriatric patients
Perhaps the most effective approach to increase enrollment of older adults is to conduct trials specifically for older adults. Studies confined to older patients can address questions of particular interest to older adults (eg, preservation of function) and increase our knowledge of tumor biology and the effect of comorbid conditions in the geriatric oncology patient population.
For example, because age is the major risk factor for breast cancer, one study for women with early-stage breast cancer who were 65 years of age or older found that standard adjuvant chemotherapy was superior to a monochemotherapy. Other studies are underway to assess the efficacy and tolerability of new drugs 1) in unfit and frail participants 80 years and older with previously untreated diffuse large B-cell lymphoma, and, 2) as an adjuvant alternative to chemotherapy in patients with high risk breast cancer 70 years and older.
People are living longer and this growing patient population needs innovative treatments tailored to the needs of aging bodies, which is why clinical research must include elderly patients. A Cancer and Aging Research Group conference report says it well: “Older age alone should not be a contraindication to clinical trial enrollment.” While the barriers to inclusivity are complex and multifaceted, it’s long past time to tear them down and develop new approaches to research that will lead to evidence-based care for geriatric patients with cancer.
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