In a draft guidance, the FDA urges researchers to take steps to increase enrollment of adults age 65 and older in clinical trials of investigational of cancer drugs. Noting that a drug's risk–benefit profile can vary significantly across age groups, the FDA recommends including older adults in early-phase studies and modifying trial designs and recruitment strategies to make it easier for them to participate.

Older adults account for a growing number of patients with cancer, yet they continue to be underrepresented in clinical trials. To address the problem, the FDA has issued a draft guidance urging researchers to increase enrollment of adults age 65 and older in trials to better assess the risks and benefits of investigational treatments in the people most likely to use them.

“Older adults consistently represent the largest proportion of new diagnoses as well as existing cases of cancer,” says Ishwaria Subbiah, MD, a medical oncologist, palliative care physician, and researcher at The University of Texas MD Anderson Cancer Center in Houston. “Given the potential for age-related variations in pharmacokinetics and pharmacodynamics, having adequate representation of older adults renders the findings of a trial more relevant to frontline clinical practice.”

The FDA's recommendations include enrolling older adults, especially those age 75 and older, in early-phase studies and evaluating potential drug interactions early in the development process; giving more consideration to older adults when designing trials and recruitment strategies; collecting data specific to older adults during trials; and including older adults in postmarketing studies.

The draft guidance and information on how to submit comments are available online.

Currently, patients age 65 and older face significant logistical barriers to trial participation, says Ellen Ritchie, MD, a hematologist-oncologist and researcher at Weill Cornell Medicine and NewYork-Presbyterian in New York, NY. “It can be a real hardship for these patients to travel to an academic medical center multiple times for treatment,” she says. “Many depend on an older spouse or other family member to take them to appointments and help them adhere to medication regimens—the caregiver plays a huge role in our ability to enroll older patients.”

To ease the logistical challenges, Weill Cornell's hospital is affiliated with a hotel to accommodate longer stays for treatment. In addition, Ritchie works closely with trial sponsors to allow greater flexibility in the timing of follow-up visits and works with physicians to schedule visits closer to patients' homes, when appropriate.

Trial eligibility criteria is another roadblock to participation, says Subbiah, citing a recent study that found that the median age of patients in more than 300 randomized trials involving four common cancers was 6.5 years younger than the median age of the general population with the same diagnoses.

“Criteria often specify a level of organ function, comorbidities, prior malignancies, and concurrent cancers and medications,” she says. “Such criteria have a disproportionate impact on older adults who will naturally demonstrate the clinical consequences of six or more decades of life.”

Paying careful attention to each criterion can help mitigate these challenges, she says. For example, a separate cohort could be created that accepts patients with mild to moderate organ dysfunction, or that enrolls only people age 65 and older. Researchers should also review the list of prohibited medications to ensure that it includes only those that may be affected by the study drug.

“The disparate enrollment of older adults has been widely recognized and acknowledged as being unacceptable by most of the stakeholders in the drug-development process,” says Subbiah. “This guidance from the FDA provides strategies to inform clinical trial design to ultimately mitigate this age-related disparity in clinical trial participation.” –Janet Colwell