Disparate Inclusion of Older Adults in Clinical Trials: Priorities and Opportunities for Policy and Practice Change

Abstract

Older adults are vastly underrepresented in clinical trials in spite of shouldering a disproportionate burden of disease and consumption of prescription drugs and therapies, restricting treatments' generalizability, efficacy, and safety. Eliminating Disparities in Clinical Trials, a national initiative comprising a stakeholder network of researchers, community advocates, policymakers, and federal representatives, undertook a critical analysis of older adults' structural barriers to clinical trial participation. We present practice and policy change recommendations emerging from this process and their rationale, which spanned multiple themes: (1) decision making with cognitively impaired patients; (2) pharmacokinetic differences and physiological age; (3) health literacy, communication, and aging; (4) geriatric training; (5) federal monitoring and accountability; (6) clinical trial costs; and (7) cumulative effects of aging and ethnicity.

In the past century, tremendous strides have been made in the effective management of chronic diseases through biomedical innovations, health promotion studies, and prevention trials, along with an improved understanding of pharmaceutical treatments and genetic determinants of health.¹ However, not every population benefits equally from these advancements, and disparities are perpetuated by the low clinical trial participation of vulnerable populations.^2–4 Exclusion of older adults as clinical trial participants is highly problematic, because older adults suffer the greatest health burden in the Western world, enduring disproportionately high rates of cancer,⁵ cardiovascular disease,⁶ dementia,⁷ arthritis, and Parkinson's disease.⁸ They spend 36% of total US personal health care dollars⁹ and consume 42% of all prescription drugs.¹⁰ Equitable participation in clinical trials on the basis of age, then, is vital, because it can advance medical knowledge and test the safety and efficacy of new treatments that are generalizable to aging populations.^11–13

However, older adults continue to be underrepresented in clinical trials.¹⁴ Although two thirds of cancer patients are older than 65 years, only about 25% of cancer trial enrollees have attained this age.¹⁵ Further research indicates that older adults carry 60% of the national disease burden but represent only 32% of patients in phase II and III clinical trials.¹⁶ Clinical trial participation of older adults is also low in research on Alzheimer's disease,¹⁷ arthritis,¹⁸ epilepsy,¹⁹ incontinence,²⁰ and cardiovascular disease.²¹ These failings may limit generalizability, provide insufficient data about positive or negative effects of treatment among specific populations,^3,13 and hinder much-needed access to new treatments.

The reasons for disparate inclusion of older adults in clinical trials are complex and challenging. Typically, older adults face a combination of obstacles, including comorbidities,⁴ ageism,⁴ economic constraints, underinsurance, lack of insurance,²² communication issues (e.g., hearing difficulties that interfere with telephone interviews and impaired vision that affects written surveys),^9,23 and physical immobility that constrains transportation options.^24,25 The unethical treatment of African Americans in research, epitomized by the Tuskegee Syphilis Study,^26,27 may partly explain why older ethnic minorities may be reluctant to participate in today's clinical trials, despite achievements in human participant protections. For example, though individuals from racial/ethnic minority groups comprise about a quarter of the US population, fewer than 1 in 10 participants in cancer studies conducted between 1995 and 1999 were from racial/ethnic minority groups.²⁸ We recognize that for many older members of racial/ethnic minority groups, the cumulative effect of a lifetime of poverty, racial discrimination, segregation, migration histories, and ill health creates divergent world views in older age than Whites,²⁹ which may fuel their mistrust in medical establishments and research.

We identified policy gaps from a current and historical context, and pinpointed limitations in evidence-based knowledge and practice that may contribute to disparities in older adults' participation in clinical trials. We describe policy-oriented and practical recommendations that can be applied across all clinical trial phases and disease areas. These key areas point to several short- and long-term opportunities for recruiting and retaining older adults into clinical trials. Our findings ensued from a workgroup on aging and clinical trials under the auspices of a national initiative, Eliminating Disparities in Clinical Trials (EDICT).

EDICT OVERVIEW AND TIMELINE

In July 2005, the Chronic Disease Prevention and Control Research Center at Baylor College of Medicine, in collaboration with the Intercultural Cancer Council, began an initiative to identify methods for improving clinical trial recruitment and retention in underrepresented populations (e.g., based on geographical isolation, age, ethnicity, disability). The EDICT initiative (principal investigator: Armin Weinberg, PhD) brought together more than 300 stakeholders nationally across thematic workgroups that convened at 3 national meetings, and via monthly Web-based teleconferences and in-person meetings. Stakeholder teams encompassed policy experts, federal agencies, community advocates, and academic, clinical, and pharmaceutical researchers.

The first of these meetings was held in September 2006 in Houston, Texas, with the purpose of reviewing existing data and formulating a platform for effectively disseminating policy recommendations aimed at increasing the participation of underrepresented groups in clinical trials. Nine thematic workgroups, each comprising a representative group of stakeholders, emerged from this event to identify issues and refine proposed suggestions into policy recommendations. From October to December 2007, an internal stakeholder policy review was conducted; between January and February 2008, an external stakeholder policy review—including a public comment period—was completed. In March 2008, 33 finalized policy recommendations were presented on Capitol Hill. Although the EDICT initiative pursued a broader assessment of underrepresented groups, we present the findings from a workgroup that compiled the concerns and critiques focused on older adults that were noted across the 9 thematic teams.

EMERGING THEMES AND RECOMMENDATIONS

Our policy-oriented recommendations were analyzed according to the “Three Rs”³⁰: ensuring equal enrollment (recruitment), minimizing drop-out rates (retention), and including a posttrial environment in which researchers, sponsors, and pharmaceutical companies interact with the community to provide accountability and tangible benefits (return). The workgroup considered the following questions: (1) What are the policy's strengths and weaknesses? (2) Which audiences should be targeted for behavioral change? (3) What are the policy's unintended consequences and social, political, ethical, and financial obstacles? (4) How might the policy be modified to be more effective? We present perspectives, observations, and rationales for each of the derived recommendations.

Develop Best Practices and Standardize Protocols

We recommend that the Department of Health and Human Services Office of Human Research Protections, which oversees the regulation of institutional review boards, and the Association for the Accreditation of Human Research Protection Programs (AAHRPP), should develop best practices and standardize informed consent processes for those with cognitive impairments. This would reduce ethical and legal concerns and promote equal representation in clinical trials. Specifically, we suggest that standard criteria be modified, ensuring that caregivers of cognitively impaired older adults are informed about their supporting roles in studies, and that the autonomy of cognitively impaired elders is protected. Clinical research staff must also receive ample training regarding such processes, including any Health Insurance Portability and Accountability Act implications and state, federal, and National Institutes of Health (NIH) regulations regarding the appropriate use and definition of a proxy.

According to the Alzheimer's Association, 1 in 8 persons aged older than 65 years is diagnosed with Alzheimer's disease or dementia.³¹ Alzheimer's disease and dementia interfere with cognitive abilities and, thus, with informed consent processes. Cognitively impaired individuals have difficulty making informed, competent, and voluntary decisions about participating in clinical trials, introducing ethical and legal challenges.^32,33 However, tools exist to aid researchers in identifying eligible participants among those with cognitive impairment.^34,35 For instance, a 3-item questionnaire that could be easily integrated into the informed consent process has been successfully tested in persons with Alzheimer's disease and diabetes to determine their capacity to make informed decisions.³⁵

The Health Insurance Portability and Accountability Act introduces privacy and legal concerns for patients, providers, and family members that affect the inclusion of older adults who require the consent of a proxy or caregiver.³⁶ Criteria are needed to help researchers designate the most appropriate proxies and caregivers, because caregivers' attitudes do not always reflect patients' interests or preferences³⁷ despite the fact that older adults often consult with family members before considering a clinical trial³⁸ and may refuse to sign any documents before discussing them with a family member.^39,40 However, the caregiver or surrogate may not be available, may not understand the protocol, may not desire the patient to be involved because of undue burden to the caregiver, or may act on their own misconceptions of clinical trials.¹⁰ Factoring caregivers into the informed consent process is crucial, because the number of older adults depending on caregivers is likely to increase in the future.⁴¹

Establish and Reinforce Guidelines

We recommend that federal mandates require age-related pharmacokinetic disclosures on all labels for all medications (i.e., improved geriatric use labeling), without exception. Pharmacokinetic and age-based differences contribute to the risk of poorly designed clinical trials that do not evaluate an inclusive participant pool.⁴² Stringent eligibility criteria may inadvertently limit enrollment of older adults with multiple morbidities, which is common in older adults.⁴³ Indeed, adults may face organ abnormalities or lower functional status with increasing age, particularly with respect to the instrumental activities of daily living and corresponding number of comorbidities.^15,39 Kidney function, for instance, may decline in older adults, impairing drug excretion and metabolic clearance of drugs.⁴⁴ In older type 2 diabetes patients, a higher prevalence of comorbidities, tolerance of adverse effects from medication, and changes in metabolic control requires a modified treatment approach.⁴⁵

The Social Security Administration and Medicare are examples of entities that have long retained antiquated definitions of old age (e.g., ≥ 65 years) based on chronological age. Scientifically, however, these age thresholds are arbitrary and uninformative for the purpose of delineating constructive clinical guidance on treatment decisions. Even when clinical trials provide an adequate representation of chronologically older adults, they describe a disproportionately healthier group than the average older-age population. Clinical trials designed with physiological age in mind would certainly lead to more meaningful results. Admittedly, the science for determining physiological age is poorly defined and inexact. Investigators only recently identified potential biomarkers that are highly predictive of chronological and physiological age in worms; the science in humans remains unreliable and subjective at best.⁴⁶ Until we acquire and test more sophisticated measures of physiological aging, to minimize biases in clinical trials from healthier populations of older adults, we support the Food and Drug Administration's (FDA's) recommendation that clinical researchers proactively include older adults aged 75 years and older, which the literature reports as suffering from a significantly higher rate of disease burden than younger older adults.

Phase I trials may not necessitate representation of older adults with high-risk complications. However, adequate enrollment of older adults in phase II and III clinical trials is essential, because of the goal of confirming dosage, safety, adverse effects, and effectiveness. Further, similar to successful pediatric-specific trials, future research in older adults may wish to investigate any advantages and disadvantages of geriatric-specific clinical trials to help elucidate the safety and effectiveness of drug and other therapies in this growing population.

Physiological age is also affected by comorbidities, quality of life, predicted life expectancy, and a patient's perceived benefits and discomfort, which may all become adversaries to treatment. Studies examining pharmacologic differences between “fit” and “frail” older adults are also needed. Fit elderly are defined as those who meet standard eligibility criteria and are capable of tolerating experimental treatment during clinical trials.⁴⁷ However, there is little discussion about “frail” elderly who are less likely to participate in clinical trials.⁴⁸ Frail elderly have reasonable functional status, with some degree of comorbidity. Clinical trial researchers must ensure the adequate representation of older persons with and without comorbidities to glean an accurate examination of a treatment's safety and efficacy.

Older adults are at high risk for adverse drug reactions because of the pharmacokinetic and pharmacodynamic changes associated with aging.^48,49 Data suggest that 19.6% of older veterans received at least 1 drug deemed inappropriate according to the 2006 criteria in the Health Plan Employer Data and Information Set.⁵⁰ To remedy this, the FDA issued its Guideline for Industry⁵¹ to encourage the fair representation of elderly participants in clinical trials. The document emphasized the importance of considering common conditions related to aging, such as renal impairment, the significant inclusion of people aged older than 75 years in clinical trials, and the study of interactions with other commonly prescribed medications in older adults. Guidance for Industry⁵² covers various drug classes believed to pose problems in geriatric patients, but it does not require manufacturers to include sufficient numbers of geriatric patients in clinical trials. The guidelines merely allow manufacturers to state in the package insert that insufficient numbers of geriatric patients were included in the trials preceding FDA approval.⁵³

The FDA still fails to require continued clinical trials for older adults with comorbidities who use high-risk drugs. Nevertheless, the tone of their amendment represents a more aggressive stance on noncompliance, which may be an important step toward inclusivity and reducing disparities arising from poor study design. The FDA's guidelines for geriatric labeling have increased awareness of the need for more older adults in clinical trials and more information on common or hazardous adverse effects among older adults. In 1998, the FDA released draft guidelines that specified the content and format for geriatric labeling on medications.⁵³ The proposal stipulated that pharmaceutical manufacturers submitting new drug applications also include geriatric labeling supplements in package inserts, subject to FDA approval. However, agency approval is not required if insufficient data exist on whether older patients react to the drug differently from younger patients.⁵³

The FDA's guidelines for geriatric labeling are problematic because of the insufficient numbers of elderly people in premarketing clinical trials. About half of all drugs marketed after 1998 contain information on use by older patients, but few describe specific problems encountered in this population.⁵⁴ In fact, only 28 of the top 50 oral medications prescribed to older adults had age-specific dosing information available, and only 8 of those included specific milligram recommendations.⁵⁵

Employ Age-Friendly Methods of Communication

We recommend that clinical trial sponsors require that researchers use consent forms, promotional materials, and other study forms in age-appropriate formats and adjusted literacy levels. This includes large-print, third- to fifth-grade reading level materials, accompanying audiovisuals for the hearing- and vision-impaired, and other clinical teaching aids that are appropriate to culture and literacy level (e.g., videos, charts, and diagrams). Trials should procure or facilitate access to supportive services, such as a participant navigator trained in geriatrics, additional funding for transportation, and access to benefit eligibility counselors. With updates pertaining to older adults, the National Standards on Culturally and Linguistically Appropriate Services, developed by the Office of Minority Health, can be used as a starting point.

Physical health impairment and low health literacy are major barriers to clinical trial enrollment for older adults. Lee et al.⁵⁶ found that low health literacy (the ability to read and comprehend basic health-related materials⁵⁷) was common among community-dwelling Medicare beneficiaries enrolled in a national managed care organization. Older adults have poor functional health literacy overall,⁵⁶ even after visual acuity and medical conditions are accounted for, and those with inadequate health literacy are likely to be older ethnic minorities with a lower annual income, fewer years of education, and a higher mortality rate.⁵⁸ African American and Hispanic patients have consistently lower rates of health literacy than non-Hispanic Whites, even after factors such as education are accounted for.⁵⁹ Those with low health literacy and chronic diseases also know less about their diseases and plausible treatment methods, and exhibit poorer self-management and health overall.^57,59 The National Standards on Culturally and Linguistically Appropriate Services provide principles of culturally competent care, issued by the US Department of Health and Human Services' Office of Minority Health.⁶⁰ These standards presently only address the language of materials and communications, and do not provide guidelines specific to older adults with low literacy levels or hearing and vision impairment.⁶¹

Support Geriatric Education and Training

We recommend that the Liaison Committee for Medical Education, which addresses education regarding clinical research, amend medical education requirements and curricula objectives to sensitize future practitioners to the special needs of older and ethnic minority adults. The Accrediting Council for Continuing Medical Education and the Accrediting Council for Graduate Medical Education should consider working with the American Geriatrics Society to adopt additional coursework and continuing education concerning geriatrics, ageism, and the intersection of age and clinical trials. The AAHRPP should reinforce these criteria by requiring that all personnel involved in a clinical trial complete training in the recruitment and retention of a geriatric population.

Biases and ageism manifest as systemic barriers that impede minority elder enrollment in clinical trials.⁶² Health care providers are less likely to refer older ethnic minorities for screening and treatment, including those provided by clinical trials.^63,64 A prevalent notion expressed by researchers is that older adults are less willing to participate in clinical trials than are younger adults.^64,65 However, studies indicate that many older people want to participate in trial research and describe such participation as a positive experience, even when studies have neutral or negative outcomes.^11,62,66,67

In a 2006 survey of 89 national colleges and schools of pharmacy, 43% of schools reported having 2 full-time geriatrics faculty members, whereas the rest relied on part-time faculty.⁶⁸ Of 125 accredited medical schools, only 12 teach geriatrics as a separate required course, only 14 have mandatory geriatrics clerkships, and most mix geriatrics training into regular coursework.⁶⁸ Two major obstacles to sound geriatric medicine programs are lack of research faculty and meager monetary incentives.⁶⁹ The lack of specially trained providers to meet the needs of the aging population is expected to worsen unless we invest in geriatric education.⁶⁹ Meager preparation among clinicians and researchers can lead to care that is unsuitable for older adults, as well as lower rates of clinical trial participation in this population.⁶⁹ Compounding this problem, the AAHRPP, the accrediting body for institutional review boards, does not require training on the equitable participation of underrepresented groups in clinical trials, nor does it make accrediting decisions on the basis of institutional review boards' performance in this area.⁷⁰

Improve Federal Monitoring and Accountability

We recommend that clinical trial sponsors require, and enforce, clinical researchers to report age by strata to document adequate representation of older adults in clinical trials. A promising policy aimed at addressing inclusion criteria in clinical trials is the NIH Revitalization Act of 1993, which mandated that women and minorities be included in NIH-funded studies involving human participants, and allowed for subset analysis by gender or race and ethnicity.⁷¹ This legislation, however, does not include recommendations regarding older adults. To begin to adequately document representation of older adults' involvement in clinical trials and conduct analysis based on specific age strata, an additional inclusion policy that provides for oversight ensuring proper implementation (i.e., uniform reporting of inclusion of older adults for all studies) should be adopted.

The FDA provides some guidance on the reporting of clinical trial data by age.⁷² The recommendations encourage drug sponsors to report the age of each clinical trial participant to allow for identification of differences in safety and effectiveness associated with age. The recommended age-reporting formats include average age, the ages of the youngest and oldest participant, and the number of participants who fall into specific age categories.⁷² Additionally, clinical review summaries provided to the FDA contain safety and efficacy data reported by age, gender, and race/ethnicity.⁷² These guidelines are easily transferable and can be adopted by clinical trial researchers.

Reduce Clinical Trial Costs

We recommend that changes be made to the cost coverage of clinical trial participation, particularly by the Centers for Medicare and Medicaid Services (CMS). The number of Medicare beneficiaries more than doubled between 1966 and 2000, and is expected to double again, to about 77 million, in 2030.⁷³ In most cases, clinical trial patients receive drugs and trial-specific care at no cost. However, they may be held responsible for some routine care associated with the trial and the cost of travel and initial screening visits. Further, because some health plans define clinical trials as experimental, health insurance coverage may not include the costs of routine patient care that is part of the trial.⁷⁴

In 2000, an executive mandate from President Clinton created an amendment to Medicare policy that required the coverage of routine patient care costs associated with clinical trials. This policy change successfully increased clinical trial enrollment for older patients from 25% to 38% between 1993 and 2003. Most of this increase, however, may have occurred among Medicare beneficiaries with supplemental private insurance coverage and may not have included underrepresented groups.⁷⁵ CMS revisited the national clinical trial coverage decision in July 2006 to address issues associated with the policy, such as clarifying payment criteria for procedures associated with clinical research.⁷⁵ During the public comment phase, some urged CMS to add criteria for including underrepresented groups in clinical trials. Ultimately, CMS made no changes to its original 2000 clinical trials policy.⁷⁵ It noted that doing so without adequate time to fully scrutinize the new FDA Amendments Act might risk duplicating contingencies stipulated by Congress.

To alleviate out-of-pocket costs, a growing number of states have passed legislation that requires health plans to pay for the routine medical care of clinical trial patients. According to the National Cancer Institute, 20 states provide mandatory third-party reimbursement for clinical cancer treatment trials.⁷⁴ Unfortunately, only 8 states offer coverage through all 4 phases of the clinical trial process,⁷⁴ and of the states that provide clinical trial coverage, several stipulate specific requirements. In California, coverage only applies to routine patient care costs related to clinical cancer trials with a therapeutic purpose, as recommended by a treating physician. To be eligible for coverage in Connecticut, clinical trials for cancer prevention must include a phase III trial with therapeutic interventions conducted at multiple institutions and approved by a federal authority. Other states, such as Georgia, only require third-party coverage for routine patient care costs incurred in conjunction with children's clinical cancer trials.⁷⁴

Respond to Effects of Race/Ethnicity and Age

We recommend that health care researchers address some of the damaging legacies of medical research among members of racial/ethnic minority groups to successfully recruit and retain them in clinical trials. Racial/ethnic minorities will make up the largest segment of the older adult population by the year 2050.⁷⁶ African Americans and Latinos, in particular, are disproportionately affected by chronic illness, disability, depression, poverty, and substandard quality of life.⁷⁶ Throughout time, members of racial/ethnic minority groups, children, prisoners, and poor people have been exploited for unethical medical research, without their consent or knowledge. Thus, inherited beliefs about the hazards associated with research and the structured inequality of the medical establishment are common among ethnic minority elderly.⁷⁷ Racial/ethnic minority group members have historically been reluctant to participate in clinical trials. Older African Americans, in particular, are more likely than older Whites to be familiar with the negative legacies of clinical research, such as the Tuskegee Syphilis Study.^26,27 These past abuses of power leave many African Americans guarded against enrolling in clinical trials. In addition to distrust of the medical establishment, older members of racial/ethnic minority groups express concern that clinical researchers lack an understanding of their beliefs and values; they also express a lack of encouragement from their physicians, and fear adverse effects of medical experimentation.^27,78,79

Compared with the general older-age population, older persons from racial/ethnic minority groups have lower health literacy rates,⁵⁶ higher poverty, and higher rates of morbidity²² that serve as barriers to participation in clinical trials. In addition to limited access to health care, cultural and language barriers, a lack of financial incentives, and unawareness of clinical trials, racial/ethnic minority group members experience more chronic illness and disability than non-Hispanic Whites, which may disqualify them from clinical trials.^80–84 Some cultures see illness as more multidimensional—encompassing religion, spirituality, and environment—than the medical establishment does, which may further inhibit access to treatment.⁸⁵

Increasing the pool of racial/ethnic minority physicians is an important and often-cited step toward creating a culturally competent health care workforce, but it is not always sufficient to overcome barriers to access. For instance, a cross-sectional study of 742 physicians' attitudes and practices regarding clinical trials found that Latino physicians were significantly less likely to refer patients to clinical trials or find scientific value in trials.⁸⁶ They reported fewer patients inquiring about clinical trials, and more who were deemed ineligible after referral. Similarly, simply having African American clinicians as the faces of a clinical trial may not produce the intended effects, if we recall that African American clinicians were responsible for executing the disastrous Tuskegee Syphilis Study protocol.

Cultural competency must encompass attention to differences in language, culture, and socioeconomic background. It also necessitates an awareness of historical context and relationships with the medical community that have consequently led to distrust of healthcare research by racial/ethnic groups. Opportunities for researchers to emulate best practices do exist. One prime example comes from the Resource Centers for Minority Aging Research (RCMAR), first funded by the National Institute on Aging in 1997, which have spearheaded studies leading to best practices in conducting research with older ethnic minorities. Their efforts have focused on developing trust among racial/ethnic minority older adults and providing possible solutions to recruiting and retaining older adults from racial/ethnic minority groups in clinical trials.⁸⁷ RCMARs have also increased the number of researchers who specialize in health of older adults from racial/ethnic minority groups, and enhanced diversity and cultural competency in the professional workforce by mentoring racial/ethnic minority academic researchers.

The Resource Centers for Minority Aging Research's focus on community-based participatory research brings in the vital perspective of community members and includes one-on-one advising, directed pilot research projects, and group feedback. This approach has proven to be effective in attracting individuals from racial/ethnic minority groups and older adults.⁸⁸ However, researchers have concluded that as beneficial as community-based participatory research can be in reaching underrepresented groups, it is also an arduous, long-term process that requires considerable commitment and buy-in from collaborators in the academic sector and the community at large.⁸⁹

FUTURE DIRECTIONS AND PRACTICAL IMPLICATIONS

Strategies for increasing older adults' participation in clinical trials must consist of programmatic and study design changes.^7,90,91 Successful recruitment requires identifying and consulting individuals who are knowledgeable about and trusted by members of the aging community,^92,93 adhere to the principles of community-based participatory research,²⁶ engage the community as a partner,^92,93 recognize cultural perspectives,⁹⁴ and provide clear and adequate information regarding risks, benefits, costs, and time required to participate in trials.⁶ Successful recruitment must also address issues of awareness, lack of resources, physical barriers, distrust of researchers, and ageism among researchers.^95,26 These strategies, however, must be backed by relevant policy at institutional and federal levels to achieve widespread and sustained impact.

Approximately 19.3% of Americans will be aged 65 years or older by 2030, a significant increase from 12.6% in 2007.⁹⁴ Additionally, because individuals from racial/ethnic minority groups will comprise the largest segment of the older-adult population by 2050⁷⁶ and are disproportionately affected by chronic illness, disability, poverty, and poor quality of life, it is imperative that policy makers, clinical researchers, federal regulatory agencies, funders, caregivers, and the general public be apprised of the importance of equal representation by age and race/ethnicity in clinical trials.

Our recommendations are not intended to address all aspects of this important issue but to invigorate a dialogue around policy-driven solutions. We are cognizant of the resistance to adopting unfunded mandates. However, we contend that when researchers and policy makers incorporate elements of these policies early in the design and development of research, higher costs can be averted. If one considers the legal and ethical ramifications of prescribing treatments on the basis of inaccurate evidence, cost should not be an excuse to avoid testing and enforcing these recommendations. Most drug therapy trials are funded by pharmaceutical companies, placing on them the larger burden of ensuring drug safety. Pharmaceutical companies face lawsuits for various reasons, from concealing crucial and sometimes detrimental study results to distributing drugs that cause adverse reactions or even death. This provides an incentive for ensuring that drug safety takes precedence and that the study population adequately reflects those who represent the consumers of such therapies.

Our recommendations, though not prescriptive, provide some guidance for developing a coordinated and comprehensive approach to reducing significant health disparities and highlight noteworthy areas for further investigation. One of the many effects of an aging population is that more people will require safe, affordable treatments for longer periods of time. A multipronged policy approach will help us achieve this goal while improving the quality of life of thousands of Americans, saving great financial and human costs in the long run.