Oncology trials should include more older people and especially those over 75 years of age, according to new guidance issued by the US Food and Drug Administration (FDA).
In advice directed at industry and clinical trial committees, the FDA says people over the age of 65 are underrepresented in cancer clinical trials despite representing a growing segment of the population of cancer patients.
The lack of inclusion means that many of the findings of clinical trials cannot be generalised to older patients who may differ in both drug response and toxicity due to age-related physiologic changes, the FDA warns.
“It is important that the spectrum of older adults included in clinical trials are representative of the intended population, including those with physiological decline (e.g., frailty). Furthermore, there may be important differences in efficacy in older adult patients compared to the younger or general population, and information describing such differences should be conveyed to patients and healthcare providers where appropriate,” it says.
In its advisory, the FDA notes that while clinical trials may not have specific exclusion criteria for older patients, many are excluded due to other criteria such as comorbidities and co-medications that are more common in older age groups. It cites a recent review that found in FDA registered trials only 36% of participants were over 65 and only 9% over 75.
The FDA says that a strategy for inclusion of older patients must be applied to all phases of clinical trials, from early phase studies through to postmarketing surveillance. It suggests oncology trial design should include provisions for older patients, with approaches such as stratifying by age and evaluating effectiveness and safety for different age groups.
Also, clinical trial committees should develop recruitment strategies targeted to older adults such as suing more accessible community-based trial sites and consider collecting additional information for older adults such as functional status and cognitive function, the FDA suggests.
Older patients in oncology trials may experience a different range of adverse effects and therefore additional strategies in adverse event monitoring and management should be included, the FDA statement advises.
“Clinical trials should include study populations reflecting the intended population that may receive the intervention being evaluated, if approved. In general, to achieve an unbiased estimate of treatment effect in the general population, sponsors should develop a strategy to enroll diverse populations, including different age groups, that are consistent with the intended use population.”
“For most cancers, clinical trials should include a representative population of older adults. Older adults, including those with physiological decline, should be enrolled in all phases of clinical trials when they can be safely and ethically enrolled,” it concludes.
However the FDA guidance remains voluntary ‘advice’ and is not being enforced with any mandatory commitments for registration of trials. Some researchers have recently suggested that underrepresentation of older adults in cancer clinical trials will persist without regulatory enforcement.
“The FDA could exert the maximum influence allowed to require submission of data related to the treatment of older adults, particularly when older or frail patients account for a substantial proportion of people with a given disease,” wrote Dr Monica Bertagnolli of the Brigham and Women’s Hospital, in a commentary in NEJM in September 2021.
“The FDA could also consider outlining postmarketing commitments for sponsors when data from registration trials don’t sufficiently address a drug’s safety and efficacy in older adults. Congress would need to authorize the FDA to enforce some of these guidelines and policies. We believe these measures would represent important progress toward promoting equity for older adults with cancer,” she wrote.