3

Conclusions and Future Research Directions

The ongoing study of pharmacokinetics, pharmacodynamics, and drug interactions in elderly persons is critical for the development of safe and effective therapies and for the prevention of drug toxicities and adverse drug reactions. Aging is associated with an increase in chronic illness and anatomical and physiological changes that affect drug distribution, metabolism, and excretion. Thus, as the number of older Americans increases, it can be expected that polypharmacy in this population will have significant health, social, and economic consequences. Additionally, research should focus on alleviating the disease burden in elderly minority populations.

Box 3.1 summarizes the committee's conclusions regarding future directions for research in this field. The remainder of this chapter provides a more detailed discussion of the committee's conclusions.

RESEARCH NEEDS AND OPPORTUNITIES

Expanding the Scientific Knowledge Base

Although progress has been made in understanding the aging process, there is still a paucity of data at the intracellular, organ, system, and population levels. The impact of aging on cells and organ systems has commonly been studied in isolation; however, a more integrated approach is needed that will examine the effects of aging on the body. Pharmacokinetic and pharmacodynamic models need to be developed that encompass the entire range of changes occurring at multiple levels throughout the body.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary 3 Conclusions and Future Research Directions The ongoing study of pharmacokinetics, pharmacodynamics, and drug interactions in elderly persons is critical for the development of safe and effective therapies and for the prevention of drug toxicities and adverse drug reactions. Aging is associated with an increase in chronic illness and anatomical and physiological changes that affect drug distribution, metabolism, and excretion. Thus, as the number of older Americans increases, it can be expected that polypharmacy in this population will have significant health, social, and economic consequences. Additionally, research should focus on alleviating the disease burden in elderly minority populations. Box 3.1 summarizes the committee's conclusions regarding future directions for research in this field. The remainder of this chapter provides a more detailed discussion of the committee's conclusions. RESEARCH NEEDS AND OPPORTUNITIES Expanding the Scientific Knowledge Base Although progress has been made in understanding the aging process, there is still a paucity of data at the intracellular, organ, system, and population levels. The impact of aging on cells and organ systems has commonly been studied in isolation; however, a more integrated approach is needed that will examine the effects of aging on the body. Pharmacokinetic and pharmacodynamic models need to be developed that encompass the entire range of changes occurring at multiple levels throughout the body.

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary BOX 3.1: Major Conclusions and Future Directions Research Develop an integrated approach to researching the effects of aging on multiple organ systems Develop more sophisticated pharmacokinetic and pharmacodynamic models of multiple drug regimens and multiple drug interactions Examine the social and psychological aspects of medication use in the elderly Implement longitudinal studies of chronic use of medications by older persons Develop research databases that link health outcomes and prescription medication information, explore the feasibility of a national data resource Develop mechanisms for effectively disseminating drug-related information to health professionals and to elderly patients Recruitment into Clinical Trials Include the older and frailer segments of the elderly population in clinical trials Expand recruitment of elderly minority populations into clinical trials Capacity Building Recruit young health professionals into geriatric pharmacology and clinical therapeutics research Provide continuity of funding for young investigators Implement incentives to retain mid-career professionals Develop programs to retrain mid-career professionals in research methodologies and geriatrics The following list highlights specific areas of research that would add to the body of knowledge and clarify our understanding of the aging process especially with regard to improving pharmacotherapy. This list is by no means comprehensive, as numerous research avenues could yield important information on the impact of pharmacotherapy and drug interactions in the elderly. Areas for future research include the impact of aging, gender, genetics, and ethnicity on physiology and metabolic processes. Specifically, age-related changes in cellular transport mechanisms and extrahepatic metabolism and transport including the activity of different enzyme isoforms; biomarkers of drug exposure; mechanisms that cause variable responses to medications in aging racial and ethnic populations;

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary age-related hormonal changes affecting drug metabolism or drug sensitivity; the impact of nutrition on the aging process; mechanisms underlying diseases prevalent in the elderly (e.g., hypertension, diabetes, osteoporosis, and Parkinson's and Alzheimer's disease); in vitro models for multiple drug regimens and multiple drug interactions that may be predictive of and correlated with in vivo research; models for drug interaction related to altered reflex activity and changing homeostatic mechanisms; the potential beneficial and adverse health effects of nutraceuticals; and social and psychological aspects of medication use in the elderly (e.g., access to medications, adherence to prescription regimens), with a special emphasis on minority populations. Addressing Issues in Minority Populations Many diseases are disproportionately prevalent in elderly African-American and other minority populations. The causes and implications of this excess burden need to be more completely understood and addressed. For example, hypertension and the impact of antihypertensive medications in elderly African Americans have not been fully studied even though the morbidity and mortality is higher in this population than in other segments of the aging population. Research is needed on multiple levels (molecular, cellular, system, population) to clarify the effect of race and ethnicity on disease prevalence and on variations in the effectiveness of pharmacotherapeutic and other treatment interventions. Such research would be a valuable tool in increasing our understanding of the physiology of aging for all populations and may have implications for pharmacotherapies aimed at various elderly groups. Research on diseases and health conditions that primarily affect minority elderly populations needs to be a priority to alleviate the disease burden experienced by these populations. Recruitment of Elderly Patients into Clinical Trials In 1989, the FDA published a guideline for the inclusion of elderly persons in clinical trials (FDA, 1989). However, a number of characteristics of the elderly population may present barriers to conducting clinical trials that are representative of this population. Studies need to include the oldest segment of the population (see Chapter 2). In addition, subgroups of the elderly population should be stratified based primarily on their functional status and disease burden and less on their chronological age.

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary Recruiting minorities for inclusion in studies should be a priority, although it is important to recognize the trends toward multiracial backgrounds and the complexities associated with categorizing race or ethnicity. The workshop speakers presented many innovative ideas about increasing the recruitment of minority populations. The committee supports a number of approaches, including providing transportation, involving the minority community, providing extensive patient education, and decentralizing clinical trials (i.e.., going to patients' homes or to community centers to provide and assess treatment). In addition, collaborative efforts and consortia need to be strengthened between historically minority and other academic institutions. These partnerships will be vital to recruiting minority investigators and to attracting and sustaining minority students in research programs. Further, patient recruitment efforts can draw on the populations available to both institutions. Obtaining informed consent in elderly populations involves complex issues that need to be addressed including the extent of dementia or cognitive impairment in some elderly patients and their vulnerability to coercion. Informed consent forms have evolved into highly technical legal documents, and a reevaluation of how to best meet their original purpose is needed. Other ethical issues that need to be addressed include studies on vulnerable populations (e.g., nursing home residents) and the confidentiality of patient information. Research Methodologies and Tools Trials of acute drug use are well funded; however, there are few long-term studies that examine chronic effects and drug interactions. Inasmuch as elderly persons are living longer and may take the same medications for many years, increased postmarketing surveillance is needed to examine the effects of long-term use of drugs. Incentives to strengthen postmarketing surveillance should be considered. Some of these drugs (e.g., hormone replacement therapy, antidepressants, and lipid-lowering medications) may be used as preventive measures (e.g., treating high cholesterol levels in the absence of cardiovascular disease or prescribing hormone replacement therapy to prevent hip fractures); however, their long-term health effects are not fully known. Further, the pharmacodynamics of many of these medications are only beginning to be investigated. Research Methodologies Studying the impact of pharmacotherapy on the elderly population is often difficult from a methodological standpoint. Cross-sectional studies are problematic because confounding variables abound among the elderly, and it is difficult to distinguish the effects of aging from those of disease. Randomized clini-

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary cal trials often recruit study subjects who represent the younger segments of the elderly population, and who have fewer comorbid conditions, use fewer medications, and may be more compliant in terms of following prescription medication regimens. In addition, many studies use small numbers of patients, frequently with homogenous geographic and ethnic backgrounds. Longitudinal studies are needed that involve large numbers of patients who reflect the diversity of “real world” populations. Furthermore, studies of elderly populations should include observational studies, case-control studies, and cohort studies to take advantage of the realm of methodological approaches that are available. Studies of optimal pharmacotherapies need to consider their cost-effectiveness and delivery. Outcome measures must also be reexamined, and quality-of-life outcomes need to be considered. One workshop speaker recalled the adage that, “adding life to years is at least as important as adding years to life.” Databases Available for Research There is a notable lack of adequate databases to research the prevalence and health impact of adverse drug reactions in elderly populations. Prescription information on elderly persons is not currently linked to diagnostic information or health outcomes data. For example, state Medicaid databases are used to reimburse pharmacies for prescriptions, therefore, the data on medication utilization are quite complete and accurate. However, diagnostic information for outpatient care is often incomplete or unavailable, and is not linked to pharmacy utilization databases. Current changes underway in the health care delivery system may provide opportunities for new databases to be developed, although there are concerns that these changes may instead result in the loss of publicly available data. Trends of interest include the purchase of pharmacy benefit companies by pharmaceutical manufacturers and the increased use of managed care through proprietary health plans paid for by Medicaid and Medicare. Increased use of managed care to provide health care for the elderly offers opportunities for databases to be implemented that would link health outcomes (particularly adverse drug reactions) and prescription information, while paying close attention to patient confidentiality issues. However, these changes may instead be implemented to restructure datasets and require new levels of approval for data use or publishing. It is crucial that the larger issues involving potential censoring or loss of publicly available data on prescription drug use and health outcomes be addressed. The increased privatization of health care services for the elderly may lead to barriers to accessing datasets due to proprietary and competitive interests. An area of interest to the committee is exploring the feasibility of developing a cooperative national data resource that would expand the researcher's

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary ability to examine population-based data rather than utilizing a piecemeal approach to data collection. This data resource could include information on diagnosis, medications prescribed, clinical interventions, health outcomes, and other relevant data. Of utmost importance would be maintaining patient confidentiality. This resource could be utilized as a repository to which individual researchers could submit peer-reviewed and approved research questions. Examining the feasibility of developing such a data resource would require the input of patients, health care providers, researchers, ethicists, and other interested persons and groups. Dissemination of Information Drug-related information can be complex, and information overload is a common phenomenon among health professionals and patients. Because information regarding drug use and interactions changes rapidly, information systems should be available to health care professionals that can provide up-to-date information that is unbiased, case specific, interactive, and readily accessible. In addition, it is important to develop diverse information dissemination strategies to effectively meet the needs of the heterogeneous elderly population. The information provided should be presented in a manner that can be understood by patients who cannot necessarily process complex information, yet need to make informed decisions and understand their options for treatment. Private- and public-sector initiatives are required to address this critical challenge. Health sciences centers that focus on training medical, nursing, and pharmacy students should be used to conduct independent, unbiased research and continuing education programs for practicing physicians, pharmacists, nurses, and the interested public (Woosley, 1994). Capacity Building: Researchers and Clinicians One of the major factors limiting the expansion of research in the area of geriatrics, and particularly geriatric pharmacology and clinical therapeutics, is the small number of health professionals entering this field. This is an area in which, as demographers can attest, the patient base is expanding and will continue to grow. Quality geriatric care depends on the development of multidisciplinary teams (including nursing, physical and occupational therapy, social work) to assess the concomitant problems and implement multiple interventions. However, reimbursements do not adequately cover the time required to handle the complexity of geriatric care. A recent report by the Alliance for Aging Research (1996) found that the United States has less than one fourth the number

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary of academic physician-scientists needed in geriatrics to teach and conduct research. There is a pressing need to develop innovative approaches for recruiting and retaining researchers and clinicians. Programs are needed at many points along the career path, beginning early in the college and postbaccalaureate years to kindle an interest in the field of geriatrics and continuing throughout the professional years to retain the best investigators and clinicians available. Recruitment of minority investigators should be included within broader programs supporting young and mid-career investigators. The options available for approaching this issue include 1- to 2-year postbaccalaureate programs to provide research and clinical experience to young people considering a career in this field; opportunities for medical, nursing, pharmacy, and other health professional students to have additional exposure to geriatric treatment and research during their education; collaborative efforts between minority academic institutions and academic health sciences centers to encourage minority students to pursue a research program in this field; loan-forgiveness programs to assist young researchers with high debt loads from health professional or graduate schools; new sources of fellowships (e.g., through FDA, pharmaceutical companies, or insurance companies); increased commitment to funding from fellowship training to first awards to independent grant support; merit awards at the midcareer level and specialized sabbaticals to retrain midcareer professionals; and retraining in research methodologies during sabbaticals for midcareer level geriatricians. SUMMARY Currently there is only a limited understanding of the impact of aging on pharmacokinetics, pharmacodynamics, and drug interactions. Research is needed at the molecular, cellular, organ, system, and population levels for safer and more effective medications to be developed, delivered, and utilized by elderly persons. In addition, attention must be given to understanding and alleviating the disproportionate disease burden in elderly African-American and other minority populations. The committee's major conclusions are summarized in Box 3.1 at the beginning of this chapter. The committee discussed and reflected only on the workshop presentations and acknowledges that there are numerous research

OCR for page 35
Pharmacokinetics and Drug Interactions in the Elderly and Special Issues in Elderly African-American Populations: Workshop Summary opportunities in geriatric pharmacology that need to be explored. Research in geriatric pharmacology and clinical therapeutics will require a commitment to fund studies that can further elucidate the relationship between pharmacokinetics and adverse drug interactions in the elderly and the complex individual variability of the aging process. Increasing the knowledge base will enable more effective therapeutic interventions and improved quality of life for the growing population of elderly persons. REFERENCES Alliance for Aging Research. 1996. Will You Still Treat Me When I'm 65? The National Shortage of Geriatricians. Washington, DC: Alliance for Aging Research. FDA (Food and Drug Administration). 1989. Guideline for the Study of Drugs Likely to Be Used in the Elderly. Rockville, MD: FDA Center for Drug Evaluation and Research. Woosley RL. 1994. Centers for education and research in therapeutics. Clinical Pharmacology and Therapeutics 56(6 Part 1):693–697.