Geriatric Trials: Why Older Adults Are Left Out of Clinical Research
Older adults are the biggest consumers of prescription drugs in the country. They are also the people least likely to be in the trials that generate the evidence for those drugs. The result is a strange situation: we treat older patients with medications that were never adequately tested in their age group.
The Clarity Clinical Solutions video on geriatric trials lays out the problem in plain numbers. Adults over 65 are about 17% of the population but consume over 40% of prescription medications. Meanwhile, many trials exclude participants above a certain age, or use eligibility criteria that quietly screen out older patients with common conditions like high blood pressure, diabetes, or mild kidney impairment.
The evidence gap
The patterns of exclusion are well documented. The video notes that patients over 75 are excluded from roughly 40% of cancer clinical trials. The most common culprits are upper age limits, exclusions for comorbidities that are simply common in older people, prohibitions on the concomitant medications many older adults take, and performance status requirements that are harder for older patients to meet.
The consequence is an evidence base built on younger, healthier patients, with an unspoken assumption that the results transfer to older populations. That assumption is shaky, because aging changes how the body handles drugs.
Aging changes drug handling
Kidney function declines steadily with age. By age 80, glomerular filtration rate is typically 40 to 50% below young adult levels, according to the video. Drugs cleared by the kidneys can therefore accumulate to toxic levels at standard doses. Liver metabolism changes too, with phase one metabolism declining while phase two stays relatively preserved. Body composition shifts toward less lean mass and more fat, which changes how drugs distribute. Lower albumin levels mean more free active drug for protein-bound medications.
Without dedicated pharmacokinetic studies in older populations, dosing is largely guesswork. The video's point is direct: we are essentially guessing at the right dose for the age group that uses the most medicine.
Polypharmacy makes it worse
The average older adult takes five or more prescription medications. That creates enormous potential for drug-drug interactions, which are almost never studied in trials because most trials exclude patients who take other medications. A drug tested as a monotherapy in carefully selected patients can behave very differently in an older patient who is also on a blood pressure medication, a statin, an antidepressant, and a diabetes drug. The video calls for drug-drug interaction studies that reflect realistic medication profiles of older patients, and it is hard to argue with that.
Barriers to enrollment
Why are older adults missing? Transportation is a major reason. Many older people no longer drive or cannot easily get to trial sites. Visit schedules designed for working-age adults are a burden. Consent forms with small print and dense language are hard to read. And there is implicit bias among investigators who assume older patients are too frail or too cognitively impaired to participate.
The video adds an important counterpoint: when older adults are offered the chance to participate, they are often enthusiastic. The barrier is not willingness. It is design.
What regulators say
Regulators have recognized the problem for decades. The FDA's guideline on studying drugs likely to be used in the elderly, issued in 1989, was one of the first documents to push for geriatric data (FDA Guideline for the Study of Drugs Likely to Be Used in the Elderly). The international ICH E7 guideline, first finalized in 1994, recommends that older patients be included in clinical trials in proportion to their expected use of the drug (ICH E7: Studies in Support of Special Populations: Geriatrics). A later FDA question-and-answer document clarified how E7 should be applied, including when dedicated pharmacokinetic studies in older patients are warranted (FDA: E7 Studies in Support of Special Populations: Geriatrics; Questions and Answers).
The video notes that these guidelines have not been enough on their own. The gap persists despite them, which suggests enforcement and incentives matter as much as guidance documents.
What better design looks like
Several practical approaches can improve inclusion. Pragmatic trial designs with less restrictive eligibility criteria can enroll older patients with comorbidities. Decentralized and hybrid trials reduce the need to travel. Home-based assessments and telemedicine visits cut burden. Consent forms with larger print and clear language help accessibility. And enrichment strategies that specifically target older adults for pharmacokinetic substudies can build the evidence base without requiring enormous dedicated trials.
Comprehensive geriatric assessment deserves a bigger role. Evaluating functional status, cognition, nutrition, social support, and frailty helps identify which older patients are most likely to benefit from treatment and which face the highest risk of toxicity. The video argues for a fit versus frail distinction rather than chronological age as the guide for treatment decisions. Fit older patients often tolerate and benefit from treatments as well as younger patients. Frail patients need modified approaches.
Geriatric oncology has led the way. The International Society of Geriatric Oncology has developed guidelines for treating older adults with cancer, and multiple studies show that selected older patients benefit from standard cancer therapies as much as younger patients. The assessment-driven approach, where treatment decisions follow physiological age rather than calendar age, is becoming standard in oncology and deserves wider use across therapeutic areas.
Consent and cognitive impairment
Including older adults with mild cognitive impairment raises special considerations, but the answer is not exclusion. Valid informed consent must come from the participant if they have capacity, or from a legally authorized representative if they do not. Simple cognitive screening tools can determine capacity, and many patients with mild impairment can still take part in consent decisions with appropriate support. People with mild cognitive impairment make up a large share of older medication users, so shutting them out only deepens the evidence gap.
The bottom line
Underrepresenting older adults has real costs. Older patients may receive standard doses that are too high for their reduced kidney function. They may be denied treatments that would help them because of age-based exclusions with no scientific basis. And guideline committees have limited evidence to guide recommendations for the group that uses the most medications. Excluding older patients does not protect them. It exposes them to treatments without evidence. The fix is default inclusion rather than default exclusion, eligibility based on physiology rather than age, routine pharmacokinetic substudies, and regulators willing to enforce the guidance that already exists. Age is not a disease, and it is not a reason to leave older adults out of the research that shapes their medicine.
This article is based on the Clarity Clinical Solutions video "Geriatric Trials | Clinical Research Explained." Watch it here: Geriatric Trials | Clinical Research Explained
References
- Clarity Clinical Solutions — "Geriatric Trials | Clinical Research Explained" (framework for this article). https://www.youtube.com/watch?v=7VPchK364Fo
- ICH — E7: Studies in Support of Special Populations: Geriatrics; recommends proportionate inclusion of older patients in clinical trials. https://database.ich.org/sites/default/files/E7_Guideline.pdf
- FDA — E7 Studies in Support of Special Populations: Geriatrics; Questions and Answers. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e7-studies-support-special-populations-geriatrics-questions-and-answers
- FDA — Guideline for the Study of Drugs Likely to Be Used in the Elderly (1989). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/study-drugs-likely-be-used-elderly