Improving Medication Use for Older Adults: An Integrated Research Agenda

Ensuring appropriate and cost-effective drug use will be an important component of the agenda for future research on successful aging. Because they increase survival and improve quality of life, medications are among the most widely used and highly valued interventions for diseases of older adults. At least 85% of senior citizens use one prescription medication, and most use more than one (1). In 2002, more than 3 billion prescriptions were filled in the United States at a total cost of $183 billion, an increase of 11% from 2001 (2). Millions of older adults also use nonprescription medications and herbal therapies, which can increase the risk for adverse drug interactions and events. The use and costs of medications will probably continue to increase, driven by growing numbers of older adults with chronic diseases amenable to pharmacotherapy (3). The scope of pharmaceutical research necessary to promote successful aging will need to be considerably broader than a simple focus on new drugs. Although some research must center on the search for more effective and safer drugs, there is also a tremendous need for more research on improving the use of currently available medications. In this paper, we describe the landscape of pharmaceutical research and suggest areas of research that merit greater attention in the national quest to improve the lives of older adults. We focus on four core domains of pharmaceutical research, encompassing both the pre- and postmarketing phases of research. The Premarketing Phase Drug Discovery and Delivery One important focus of pharmaceutical research is the development of better drugs and delivery systems. The search for new chemical entities by medicinal chemists in both the public and private sectors drives the discovery of new drugs. These drugs are initially tested in animals, and promising agents undergo three phases of testing in humans before they are put on the market. Only one in five new drug applications results in a marketable drug product. Among marketable drugs, decisions about forms (for example, tablet, capsule, parenteral, or patch delivery systems) must be made with older adults in mind. Pill size, color, shape, and delivery system may each play a role in adherence. For example, intranasal administration of influenza vaccines may increase patient participation in immunization programs, and transdermal selegiline was recently found to be safer than selegiline administered in pill form (4). Drug discovery is fueled both by health care needs and by economic incentives in the pharmaceutical industry. Research and development dollars for new-drug discovery exceeded $32 billion in 2002 (5). Drug Efficacy and Safety Pharmacokinetics and pharmacodynamics are key components of clinical pharmacology. For newly marketed drugs, research on disposition and action in older adults now derives from premarketing studies required by the U.S. Food and Drug Administration (FDA). Before 1990, however, few older adults participated in the premarketing phases of human studies. Little was learned about a drug's effectiveness and problems in elders until the drug reached the market and was used by many older adults. In August 1997, the FDA published guidelines encouraging the inclusion of elderly participants in trials of drugs likely to be used to treat diseases prevalent in older patients. This led to improved labeling instructions to help guide therapeutic decisions, such as those on appropriate dosages for geriatric patients, and a Geriatric Use Subsection that contained further information specific to use of drugs in the elderly. This federal regulation provided important prescribing information to those caring for elderly patients. However, prescribing information alone is insufficient to ensure the appropriate use of drugs in clinical practice. Physicians may need information support when making prescribing decisions that take into account individual patient variables, such as current use of other prescribed drugs, renal function, cognitive function, and other factors important in judging the riskbenefit ratio of a medication (6). The Postmarketing Phase Pharmacoepidemiology and Drug Policy Premarketing studies often include too few older participants to show important adverse effects of a drug in the elderly (7). Thus, the infrequent hazards of a medication generally become apparent only after the drug is prescribed for large populations (8). For this reason, observational studies are especially helpful in determining the relation between a medication's effectiveness and its safety after marketing. Such studies require attention to important background characteristics of both patient and prescriber, some of which can be controlled by using statistical procedures, such as multivariable modeling or propensity scoring (9, 10). In practice, pharmacoepidemiology seeks to frame the benefits of medications against their potential harm in the heterogeneous population of older adults who are prescribed the drug. The United States has been slow to create the infrastructure needed to support these studies at a national level. Yet other countries have vigorously begun initiating such infrastructures (11). Adverse drug events are a common form of preventable iatrogenic injury among older adults in all care settings (6, 12). Research suggests that this is due more to the number of drugs used by geriatric patients than to the effects of aging (13). Drug-related complications are twofold greater in the elderly than in younger adults (12). Gurwitz and colleagues found that adverse drug events were common, often serious, and often preventable in ambulatory settings (6) and in nursing homes (14). Drug interactions are especially likely in elderly patients who use numerous prescription drugs coupled with self-administered interactants, such as over-the-counter and herbal remedies (15). Such interactions can cause harm or death and have resulted in the withdrawal of numerous drugs by pharmaceutical manufacturers (8). Collectively, these postmarketing studies emphasize the need for practices and interventions to reduce preventable errors of medication use, adverse drug events, and drug interactions. However, many adverse events result not from unknown effects of medications but from inappropriate prescribing. An assessment of the risks and benefits of a drug must take into account the harm that may result from inappropriate prescribing. The benefits and risks of drug products determine their value in practice and on the market. This value is relative to that of other drugs or treatments available for the same condition (16). Pharmacoeconomics research assigns this value as an aid in the development of drug policy. This research should focus on head-to-head comparisons of new and current medications commonly used for the same disorder, with the goal of identifying the most cost-effective drug. In some cases, a new, expensive drug may not be the most cost-effective (17). In other situations, although a new drug is more expensive, its overall costs may be lower if it reduces health care use; for example, if it decreases the number of hospital admissions (18). However, policymakers rarely have access to unbiased data on these topics because we lack a national infrastructure to oversee and mandate the investigations that produce such data. Thus, drug-benefit programs must often make decisions based on drug costs alone. Improving Access to and Use of Drugs The growing costs of pharmaceuticals have spurred employers' drug-benefit programs to implement drug-management efforts, including promotion of the use of generic drugs, tiered copayment programs, and capped benefit programs. Although these efforts have helped reduce costs, they have done little to reduce out-of-pocket expenses for older adults, for whom out-of-pocket expenses have been especially high (19). However, an undue emphasis on drug cost alone may be harmful in some circumstances (20). One proposed solution to high out-of-pocket costs for older persons is a national prescription plan. The costs of such a program are, of course, a major focus of debate. The U.S. government's largest drug-benefit program, Medicaid, provides prescription coverage for 11% of poor persons in the United States (21). Older adults without Medicaid often lack the resources to pay for their medications, and poor, elderly members of groups without adequate prescription coverage have suffered disproportionately because of insufficient prescription coverage (22, 23). Most elders who can pay for their prescriptions have fixed incomes and therefore increasingly lose discretionary money as costs increase (24). On the basis of these findings, drug policy proponents recommend broad drug coverage within Medicare, especially for vulnerable persons (25). However, demonstrating cost-effectiveness and improving access to medications does not ensure appropriate prescribing. Enormous gaps still exist between knowledge and prescribing practice. For example, even though unequivocal evidence from long-term effectiveness studies shows that control of hypertension reduces morbidity and mortality, only a minority of older adults with hypertension have adequately controlled blood pressures (26). The gaps are due to patient, physician, and healthcare system factors. Patient factors include poor adherence to complex drug regimens; low tolerance of side effects; and the inability to prioritize long-term health outcomes (including survival) over more proximate issues, such as avoidance of nuisance side effects or competing financial demands. Physician factors include incomplete acceptance of recommended standards of care, competing clinical demands, and barriers to effective communication with patients about the health benefits of adherence (27). System factors include lack of access to health care, high medication costs, poor longitudinal tracking data on medication use, and complicated formulari