A paradigm shift in evaluation of new medications for older adults—A mandate has arrived!

It has long been recognized that older adults may respond differently to medications than younger adults. Underlying mechanisms are potential differences in the pharmacokinetics or pharmacodynamics of medications, the presence of multiple medical conditions and potentially interacting medications, and combinations of these factors. It has been almost 35 years since the “Guidelines for the study of drugs likely to be used in the elderly” were published by the Food and Drug Administration (FDA).¹ These guidelines focused largely on pharmacokinetic differences as methods for these investigations were well developed but introduced the concept that studies to evaluate new medications should include participants that would be representative of the target patient population. Subsequent policies and statements from national, international, pharmaceutical, academic, and clinical organizations also endorsed this concept. Yet, as readers of this Journal are well aware and has been addressed previously in 2010,² older adults—and especially “typical” older adults seen in clinical practice who have multiple chronic conditions, take multiple medications, and frail older adults have been underrepresented in clinical trials of medications that treat conditions that may be common in older adults. This means that healthcare professionals really do not know how older adults may respond to a new medication at the time of initial clinical availability even though they often represent a significant fraction of the target patient population. Use of new medications in older adults often represents individual clinical trials without the benefit of the rigorous evaluation of a clinical trial or aggregation of results. Lack of comprehensive post-marketing surveillance and primarily voluntary reporting of suspected adverse events creates the possibility of either failure to recognize safety concerns in older adults or a lag time for recognition of adverse effects during real-world usage.

The lack of inclusion of older adults in trials of cancer drugs received particular attention and has stimulated the development of new guidelines for the study of older adults in cancer trials.³ The exclusion of older adults in the evaluation of vaccines for COVID-19 despite the highest toll of the virus in older adults also brought recognition of the lack of inclusion to the forefront.⁴ The increased attention focused on health disparities of racial minorities has also served to highlight the underrepresentation of racial minority populations in clinical trials of new therapies⁵ and has led to the first legislation that puts into law the concept that participants in trials represent the clinical populations with the disorder to be treated with the medication.⁶ The FDA has published guidance on clinical trial diversity⁷ and while focused on diversity, indicates that the same principles will apply to inclusion of older adults in clinical trials.

The legislation and the guidance present some new principles for how “representativeness” may be measured, for defining “older adults,” and considerations for changes in trial design to implement successful recruitment and trial completion.^{6, 7} While the legislation and FDA regulations are for the United States, there has been a policy of harmonization of many considerations and processes for drug evaluation^8-10 and changes in other countries may follow. This is the background that led to a symposia at the American Geriatrics Society (AGS) on May 5, 2023 titled: Evaluation of New Drugs: A Changing Landscape for Older Adults and Diverse Populations. The symposia addressed gaps in enrollment of older adults and older adults of minority status in clinical trials, the need for information from older adults in clinical trials of new therapies, the evolving landscape trying to fill this gap, and the important role that clinicians, researchers, and the AGS can play to increase participation of older adults in clinical trials of new medical therapies.

This special section of the Journal of the American Geriatrics Society will present summaries of the talks presented at the meeting on the US perspective from academia, the National Academy of Sciences, Engineering, & Medicine, and the FDA, and international perspectives of the European Geriatric Medicine Society, and the International Union of Basic and Clinical Pharmacology. This section will be supplemented by papers to describe the current experience and policies of the U.S. National Institutes on Aging, the European Medical Agency (EMA), of colleagues in the United Kingdom (UK) on the current state of UK policies after its exit from the European Union, and an assessment of the current gaps and unaddressed lack of enrollment of nursing home residents in clinical trials.

Now is a time for optimism. We currently have the opportunity to engage and contribute to implementation of mandated efforts to ensure the evaluation of new medications provides the information that is needed to safely and effectively treat patients of all ages, races, ethnicities, and nationalities. I and the additional authors of this special section of the Journal of the American Geriatrics Society hope you will join us in efforts to define, collect, and evaluate the data on representative patient enrollment, continue to advocate for appropriate enrollment of older adults in clinical trials and for measurement of outcomes that are important to patients.

None.