The randomized, controlled, double-blind clinical trial is often referred to as the gold standard by which health care professionals evaluate the efficacy of a drug. These trials should be relied upon to make treatment decisions because they are the only study design that can truly prove cause and effect between the drug and the outcome of interest. The elderly are high utilizers of prescription drugs; however, they are often only a small percentage of subjects within the clinical trials. It then becomes challenging to apply these trial results to this population, particularly considering their vastly different health profiles from the younger population.
Who is Considered Elderly?
The definition of “elderly” varies. There is no universally accepted number, but it has been suggested to be as low as 50 years or as high as 70 years. Of course, this number is different depending on which country or nation you are discussing. In the United States, the Centers for Disease Control (CDC) track the average life expectancy. For the years 2009-2011, this number was 78.6 years for the total population. Quite a contrast from the life expectancy in 1900 of only 49.2 years.1 The number of persons aged 65 years and older was 16.5% of the population in 2019.2 This number will continue to grow as the baby boomers “age” and medical technology improves. Many people now expect to maintain their quality of life well into their eighties and nineties.
Low Representation of the Elderly in Clinical Trials
Two classes of drugs that are commonly used in the elderly include the angiotensin-converting enzyme inhibitors (ACEIs) and the angiotensin receptor blockers (ARBs). Although they are used to control hypertension, a more meaningful outcome is a reduction in cardiovascular events in patients with heart failure. A recent meta-analysis of randomized controlled trials combined results from 38 studies with over 47,000 subjects. Mean age of participants ranged from a low of 58 years to a high of 73 years within these individual studies. Only 4 of the 38 studies stated a mean age of over 70 years. This is concerning and calls into question the generalizability of results to our older patients.3
A similar situation exists for the use of inhaled therapies for chronic obstructive pulmonary disease (COPD) to reduce risk of exacerbation (inhaled corticosteroids [ICS], long-acting beta2-agonists [LABAs], and long-acting muscarinic receptor antagonists [LAMAs]). A meta-analysis was conducted utilizing 14 randomized, controlled trials with almost 17,000 subjects. Mean age of participants ranged from a low of 61 years to a high of 73 years within individual trials, with only 1 trial reporting a mean age of over 70 years. Again, this is an issue, considering the higher prevalence of COPD in adults over 70 years.4
Special Considerations in the Elderly
Regardless of how you define the elderly, special considerations come into play regarding selection of drug therapy in this group. Generally, organ function declines with age. Reduced hepatic and renal function may significantly impact drug metabolism and excretion. Older adults are more susceptible to adverse reactions. Polypharmacy is common, along with increased risk of drug interactions. Nonadherence may be a concern. Lastly, there is wide inter-individual variations in age-related changes, co-morbidities and treatment settings (home versus long-term care).5
What should clinicians who prescribe drugs in the elderly do when clinical trials do not have sufficient information about the results of the use of the drugs in the elderly population? Results from clinical trials in which the elderly population is noticeably underrepresented should be used with caution in making treatment decisions. There is often not enough information to ascertain if outcomes or side effects would differ in important ways from those seen in younger patients. Determining starting dosages and titration schedules of individual patients, as well as expectations of risk versus benefit, is largely left to the clinician’s judgment and personal experience. Even product specific information is often lacking in this regard. Physicians and other clinicians may find it appropriate to adhere to the old mantra to “start low, go slow” when treating elderly patients.
A Call to Action
Inclusion of “special populations” in clinical trials continues to be a challenge. For reasons too numerous to mention here, gaps in participation are not only apparent for the older patient, but also the younger patient, those in rural communities, and minorities. Health researchers have made it a priority to define special populations and determine better means of recruitment. There is also the recognition that the clinical trials should match the health priorities of the target population. It is hoped that adoption of best practices in this regard will improve our ability to draw conclusions that can benefit all populations, including the elderly.6
Although it has been more than 10 years, a national initiative was undertaken to form the Eliminating Disparities in Clinical Trials (EDICT) workgroup to identify opportunities for recruiting and retaining older adults into clinical trials. Some progress has been made, but more work needs to be done to implement their original recommendations: 1) standardize the informed consent process for people with cognitive impairment, allowing for caregiver input; 2) establish and reinforce guidelines requiring improved geriatric use labeling on all medications and active recruitment by industry of elderly patients into clinical trials; 3) provide age-appropriate communications and supportive services; 4) invest in geriatric training at the researcher and practitioner level; 5) require clinical researchers to adequately document age stratification; 6) minimize cost to patients for participation in trials; and 7) develop strategies to increase enrollment by racial/ethnic minority groups.7
There is still a knowledge gap in the evidence-based medicine arena for the geriatric patient. Healthcare practitioners should encourage their elderly patients to sign up for clinical trials, providing information and honest answers. Only then can we hope to fill that knowledge gap and provide the best care possible for our treasured seniors.
- Arias E, Miniño A, Curtin S, Tejada-Vera B. U.S. decennial life tables for 2009–2011, United States life tables. National Vital Statistics Reports; vol 69 no 8. Hyattsville, MD: National Center for Health Statistics. 2020.
- United States Census Bureau. Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045219. Accessed on October 29, 2020.
- Tai C, Gan T, Zou L, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular events in patients with heart failure: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2017;17(1):257. Published 2017 Oct 5. doi:10.1186/s12872-017-0686-z. Accessed on October 29, 2020.
- Cazzola M, Rogliani P, Calzetta L, Matera MG. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis. Eur Respir J. 2018 Dec 13;52(6):1801586. doi: 10.1183/13993003.01586-2018. PMID: 30309975. Accessed on October 29, 2020.
- Delafuente JC. Pharmacokinetic and pharmacodynamic alterations in the geriatric patient. Consult Pharm. 2008;23:324-334.
- Winter SS, Page-Reeves JM, Page KA, et al. Inclusion of special populations in clinical research: important considerations and guidelines. J Clin Transl Res. 2018;4(1):56-69. Published 2018 Apr 7. Accessed on October 29, 2020.
- Herrera AP, Snipes SA, King DW, Torres-Vigil I, Goldberg DS, Weinberg AD. Disparate inclusion of older adults in clinical trials; priorities and opportunities for policy and practice change. Am J Public Health. 2010;100 Supp 1:S105-S112.