US Pharm. 2007;32(10):20-25.

Astonishingly, it is frequently observed that the efficacy and safety of new pharmaceuticals are evaluated in patient populations with significantly different characteristics from some of the patients for whom the treatments will be prescribed in clinical practice.1 Furthermore, geriatric patients enrolled in clinical trials represent a fractionated, heavily biased subcategory that is not typical of the general senior population.2 This holds true even though the majority of medications prescribed to the elderly have previously been tested through randomized, controlled trials on a younger and biologically different group of patients.3 Clinical trials frequently include younger adult subjects with a single pathology, while patient care in the real world is populated by older adults with multiple comorbidities.1

As age increases, so does the number of comorbidities. The estimate ranges from 2.9 comorbidities for patients ages 55 to 64 years to 4.2 in patients 75 and older.2 It follows, therefore, that multiple medications are required to manage the conditions in these individuals. It has been estimated that the majority (78%) of individuals older than 65 take medications and that some (39%) are regularly on five or more medications; approximately 90% of patients in this age group are also reported to take OTC medications.2 As comorbidities increase and the number of medications increases, so too do the risks for adverse reactions and drugñdrug interactions; ultimately, an increased risk of impaired treatment efficacy and/or drug-related toxicity will ensue.2 Clinical trials that enroll the elderly would reveal specialized information clarifying the specific dose and duration of therapy that would deliver efficacy while minimizing adverse reaction risk in this population.

Clinical Trials and Seniors
Today in the United States, there are 37 million people older than 65, accounting for more than 13% of the population; this compares with 4% of the population older than 65 back in 1900 and more than 20% of the population--approximately 80 million seniors--estimated for 2026.4 And while seniors are in better overall health than their predecessors, the oldest individuals experience the most dramatic decline.4 This makes it all the more urgent to study new pharmaceuticals in the geriatric segment of the population before these agents are released into the marketplace.4

Approximately 60% of all new cancer cases and 70% of all cancer-related deaths occur in those 65 and older, and by the year 2030 this absolute number is estimated to double.5 Why, then, are the elderly frequently underrepresented in clinical trials of new cancer treatments and less likely to receive definitive or adequate cancer therapy when they are at the greatest risk for this disease?6 It is probable that a variety of strategies may be needed to evaluate cancer therapies for the elderly in prospective clinical trials and to improve cancer care in this population.6

One study, evaluating the impact of age on patient enrollment in clinical trials for registration of new cancer drugs or for new cancer indications approved by the FDA from 1995 to 2002, found that the percentage of elderly patients enrolled in the registration trials was significantly lower than the corresponding rates in the U.S. general cancer population for each cancer type. 6 The only exception was in breast cancer trials of hormonal therapies. 6

The enrollment of patients in adequate number and with appropriate characteristics for proper analysis and generalization of results to the intended population is an essential requirement of clinical trials.6,7 Elderly patients, including those 70 and older, should be included in moderate numbers in the studies of pharmaceuticals with probable use in seniors, especially since random restrictions based on chronological age are no longer applied to clinical trials.6,7

Experts have advocated for an end to this "serious and expensive mistake" by encouraging 1) clinical research to focus on a population that represents the intended and genuine one; 2) the pharmaceutical industry to develop agents designed specifically for seniors and studied in geriatric patients; and 3) regulatory agencies (i.e., the FDA, the European Agency for the Evaluation of Medical Products) to develop and approve drugs tested and validatedon patients with similar characteristics to the ultimate consumers.2

Age-Related Medication Problem
In spite of the benefits of pharmacotherapy, medications are more likely to cause problems in the elderly, potentially compromising health-related quality of life. Drugs affect the organ systems of seniors differently from those of younger adults. Physiologic ageñrelated changes, such as decreased renal and hepatic function, decreased responsiveness and number of receptors, and decreased peripheral nervous system responses, can cause exaggerated responses to medication, changes in drug levels, and increased susceptibility to drugñdrug interactions.4 Furthermore, as a consequence of these changes, seniors are exposed to a three- to 10-fold risk of adverse drug reactions compared with younger individuals.2,8 These age-specific issues should be evaluated in random clinical trials with reference to the efficacy of a new pharmaceutical. This would further enhance the prescribing information available to ensure more accurate dosing and administration guidelines for this specialized population.

Criteria have been developed in the U.S. and Canada over the last 10 years for defining potentially inappropriate medication use in the elderly.9-16 Additionally, Eastern and Western European research has also targeted this focus group. One European study looked at the prevalence and consequences of inadequate medication utilization in frail senior patients and found that poverty, polypharmacy, use of antibiotics, and depression demonstrated the strongest correlation.17 This information, however, has been gathered largely by retrospective measures. Clinicians must be able to choose with confidence, based on viable evidence, the most appropriate medication regimens for their senior patients. This should be done in conjunction with appropriate monitoring for adverse effects to minimize the risk of potential multidrug interactions. Clinical trials that study agents used in the geriatric sector are encouraged to better determine pharmacotherapy parameters.

A patient's perception of the benefits and risks of medication therapy may affect adherence, a potential reason for failure of medication regimens and poor treatment outcomes.18 Neglecting to inform patients about appropriate dosage intervals and interactions with foods or medications can hinder the success of a medication regimen. Additionally, discussing lifestyle and dietary modifications before a medication is initiated, when indicated, to eliminate the need for medication intervention or to enhance pharmacotherapy, is an important principle directly related to new medication communication.

Although evidence supports the notion that medications are not taken as prescribed,few investigations have described the specific elements of communicationabout new medication therapy.19 One recent observational study, looking at patient and physician surveys in conjunction with transcribed audiotaped office visits that transpired in the outpatient setting with family physicians, internists, and cardiologists in health care systems in California, measured the quality of physician communication when prescribing new medications. Regarding the new prescriptions, physicians 1) stated the specific medication name for 74% of new presriptions; 2) explained the purpose of the medication for 87%; 3) addressed adverse effects for 35%; 4) addressed how long to take the medication for 34%; and 5) stated the number of tablets to take for 55% and explained the frequency or timing of dosing for 58%.19 Overall, of the five elements of communication, physicians counseled the most about psychiatric medications. The researchers concluded that physicians often fail to communicate crucial elements of medication use, potentially contributing to misunderstandings about the directions or necessity of patients' medications, which may lead to poor adherence.19

The principles of pharmacotherapy that guide a pharmacist's practice are to observe a patient's response to medication therapy to confirm efficacy; prevent, detect, or manage adverse effects; assess adherence to the regimen; and determine if there is a need for dosage adjustment or medication discontinuation. Underlying this responsibility, however, is the opportunity to guide patients and caregivers as to their responsibilities in becoming informed about their medication (TABLE 1). If patients leave the doctor's office without appropriate information regarding a new prescription, they certainly should not leave the pharmacy without being counseled by a professional who is trained to deliver pharmaceutical care.

While multifaceted, age-related physiologic changes affect how seniors process and tolerate pharmaceuticals, research is frequently focused on younger individuals, while seniors are often excluded from or underrepresented in clinical trials of new drugs. This occurs despite the use of these studied agents in the older adult with comorbidities in subsequent clinical practice.

By raising awareness about this issue, one would hope for more specific and prevalent evidence-based information regarding how medications are tolerated in the elderly before the third decade of the 21st century, when the elderly population will represent approximately 20% of the U.S. population. Quality physician and pharmacist communication about taking a new medication is critical to the proper use of drug therapy and patient adherence. The pharmacist's counseling intervention about new medication should continue to be a cornerstone in the delivery of pharmaceutical care.


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