Fall 2010

A Call to Action – Inform Patients of Clinical Trials
By Karen Martin, PharmD, MBA, CGP
Aging Well
Vol. 3 No. 4 P. 32

Randomized, controlled, double-blind clinical trials are considered the gold standard by which healthcare professionals evaluate the clinical efficacy of a drug or a class of drugs. They are the only study design that can truly prove the cause and effect between a drug and a particular outcome. Therefore, providers greatly rely on them to make treatment decisions. When clinical trials include only a small percentage of elder subjects, it is challenging to apply the results to all older adults, particularly considering their vastly different health profiles and higher prescription drug utilization compared with younger people.

Low Representation in Clinical Trials
An example of a drug class for which substantial outcome data are available but for which information about use in older adults is lacking is angiotensin receptor blockers. Outcomes available for this class of drugs include reduction in cardiovascular events, stroke, and the progression of diabetic nephropathy. In determining which studies provide the most relevant and reliable information regarding results in elders, certain studies can be eliminated from consideration.

Although hypertension is considered a risk factor for cardiovascular disease, it is only a surrogate marker. The pool of eligible studies can be further reduced by excluding those with poor methodology (eg, inadequate randomization, blinding, or handling of dropouts). Nine quality primary studies were found with meaningful outcomes of interest. Two of these studies excluded subjects aged older than 70. The mean age in the eligible studies was 60 to 67 years old. Only one study reported further stratification by age group. The lack of studies focusing on the senior population is concerning when we consider that this is a class of drugs that would be expected to be highly utilized in the elder population.

A similar situation exists for inhaled corticosteroids. Outcomes available for this class of drugs include reduction and exacerbation of respiratory symptoms and mortality. Studies evaluating only lung function were eliminated from consideration because this is a surrogate outcome that does not necessarily equate to symptom improvement. Three secondary studies and one primary study were found for the treatment of asthma, and four secondary studies were found for the treatment of chronic obstructive pulmonary disease (COPD). For the secondary asthma trials, the mean age was listed as between 8 and 55 years old. The primary study included asthmatic children between the ages of 6 and 15. For the COPD studies, the patient population was described as adult. Examination of the details of the included COPD studies in the secondary trials revealed an age range between 53 and 73 years old, with lack of stratification.

Similar to the studies on angiotensin receptor blockers, the lack of studies focusing on the results of inhaled corticosteroids in elders is an issue given the high utilization of these drugs in this population.

Who Are Considered Elders?
Important to this discussion is the definition of an elder and what ages are considered part of this population. There seems to be no universally accepted number. It has been suggested that it is as low as the age of 50 and as high as the age of 70. Whether someone is talking about a developed or underdeveloped nation would also be a consideration. In the United States, the average life expectancy reported in 2006 by the Centers for Disease Control and Prevention was 77.7 years for the total population. Contrast this with the median age at death of 58 years in 1900.1 The number of people aged 65 and older was 12.9% of the population in 2009.2 This percentage is expected to grow as the baby boomers age and redefine the meaning of the word, relying on their self-determination and an insistence on the latest medical technology to maintain their quality of life well into their 80s and 90s.

Special Considerations in Elders
Regardless of the age at which individuals are classified as being elders, special considerations come into play regarding the selection of drug therapy in this group. It is widely accepted that organ function declines with age. Reduced hepatic and renal function significantly impacts drug metabolism and excretion. Older adults are more susceptible to the adverse effects of medications. Polypharmacy is common in this group and can lead to nonadherence or harmful drug interactions. There are also wide interindividual variations in age-related changes, comorbidities, and treatment settings (home care vs. long-term care).3

What should clinicians who prescribe drugs for elders do when clinical trials lack sufficient information about the results of the use of certain drugs in the older population? Results from clinical trials in which the elder population is noticeably underrepresented should be used with caution when making treatment decisions. There is often not enough information to ascertain whether outcomes or side effects would differ in important ways from those seen in younger patients. Determining starting dosages and titration schedules for individual patients as well as expectations of risk vs. benefit is largely left to a 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 elder patients.

A Call to Action
Responding to this concern, 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. The EDICT workgroup has made the following recommendations: standardize the informed consent process for people with cognitive impairment, allowing for caregiver input; establish and reinforce guidelines requiring improved geriatric-use labeling on all medications and active recruitment by industry of elder patients into clinical trials; provide age-appropriate communications and supportive services; invest in geriatric training at the researcher and practitioner level; require clinical researchers to adequately document age stratification; minimize costs to patients for participation in trials; and develop strategies to increase enrollment by racial/ethnic minority groups.4

The practice of evidence-based medicine in the geriatric arena requires careful consideration. A knowledge gap exists, one that will be filled only by including adequate numbers of elder subjects in clinical trials. Practitioners can answer the call to action by offering information about trial recruitment to their patients, providing honest answers to their questions, and encouraging their participation.

— Karen Martin, PharmD, MBA, CGP, is board certified in geriatric pharmacy and a senior drug information specialist for WellPoint, Inc.

 

References
1. Arias E. National vital statistics report: United States life tables, 2006. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_21.pdf . Accessed July 8, 2010.

2. U.S. Census Bureau. State & county quickfacts, USA. Available at: http://quickfacts.census.gov/qfd/states/00000.html . Accessed July 8, 2010.

3. Delafuente JC. Pharmacokinetic and pharmacodynamic alterations in the geriatric patient. Consult Pharm. 2008;23(4):324-334.

4. Herrera AP, Snipes SA, King DW, et al. Disparate inclusion of older adults in clinical trials: Priorities and opportunities for policy and practice change. Am J Public Health. 2010;100 Suppl 1:S105-S112.