Clinical Trials in Elderly Persons

Many randomized controlled clinical trials have systematically excluded elderly persons from studies to answer therapeutic questions. For example, treatment of mild and moderate hypertension is an important clinical issue for the elderly, but major trials have excluded persons over age 69 when investigating the efficacy of treatment.1,2 A number of questions about therapy that are important to older persons could best be answered through clinical trials, but clinical trials that include the elderly invoke special problems. Future trials may not fill this void unless special attention is focused on these problems. Ethical considerations and research design can prompt exclusion of elderly persons from studies. Personal physicians may be reluctant to refer potential subjects because of a strong inclination to protect them. One concern is poor comprehension by some elderly of the information for informed consent.3 Even when appropriate subjects can be identified and recruited, advanced age complicates design. As the population ages, both the ratio of women to men and the prevalence of chronic problems increase. If the research does not reflect the age and sex distribution of persons in the elderly population, or if persons with multiple chronic problems are excluded from the study, the ability to generalize the results of the study may be questioned. For some therapeutic questions, quality of life and functional ability may be more appropriate measures of therapeutic benefit than mortality or conventionally defined morbidity, but measurement of these dimensions may be less exact and more costly. Multiple medical problems may intervene during the course of a study, and the impact of a therapy may be positively or negatively confounded by ancillary therapies or noncompliance, leading to confusion concerning outcomes. With these obstacles, one might ask whether clinical trials in elderly persons create insurmountable barriers. Perhaps geriatric research might focus increased attention on alternative methods for arriving at decisions. Should expert opinion, consensus panels, observational studies, and case-control data be substituted for controlled clinical trials? It is tempting to rely on these methods when faced with the practical problems of recruitment of an elderly population as participants and the ethical problems of performing a trial in the midst of opinions concerning the efficacy of therapy. For some questions, alternative methods may provide adequate answers. For others, they will not, and randomized controlled clinical trials will remain the best method for evaluating efficacy and effectiveness. The experiences of other clinical trials clearly illustrate the importance of properly designed and conducted trials in producing evidence for therapeutic decisions.4 Attempts to utilize alternative designs may produce different opinions about results and add to confusion about therapy. The practical problems of recruitment and design can only be resolved by planning and diligence. Investigators must prepare for the special needs and concerns of an elderly population, and trials may require special measures of therapeutic results and analyses of comorbidity, accessory treatments, and function. The ethical concerns of clinical trials in the elderly must be addressed with a perspective of the history of clinical trials and the obligations of researchers and other physicians.4 The critical question is, “Do we already know the answer to the therapeutic dilemma?” Withholding a treatment that has been demonstrated to be efficacious violates a commitment to patient welfare formally outlined in the Hippocratic Oath and is morally suspect. Clinical trials cannot be ethically supported when optimal treatment is already known. In many, if not most, circumstances, the best medical procedure has not been determined and is controversial. If the answer is not known, then a clinical trial can be ethically supported. Clinical trials must address the ethical concerns that frequently follow. The first concern is the treatment provided. A proposed experimental treatment must be reasonably suspected as being at least as good as standard treatment. It is also important that clinical trials employ standard therapy as the treatment of the control group. The control group's right to the best medical treatment requires standard therapy if it is established. Placebo therapy should only be used when standard therapy does not exist. The second ethical concern is the appropriateness of physician participation. The actions and support of individual physicians frequently create discussions concerning ethics. Physicians may have preferences for therapy and opinions concerning the hypothesis to be tested in the trial. However, preferences and unsubstantiated opinions do not constitute evidence that must be outlined for patients to satisfy informed consent. If a trial is necessary to answer a therapeutic question and the patient demonstrates the characteristics under question, then it is ethically appropriate to introduce the research project to the patient, even though the physician and/or investigator may have a hunch concerning the eventual outcome. A physician's failure to disclose a personal preference to the patient does not violate the patient's right to the best medical care when evidence is absent. However, it is imperative the potential subject understands the essence of the research issue and gives informed consent. In addition to the fulfillment of ethical considerations in implementing the trial, it is important for investigators and physicians to also recognize their ethical responsibility to support clinical trials. The utilitarian obligation of medicine to enhance the general welfare is clearly recognized. Medicine has an obligation to benefit society and provide new information for future patients. This utilitarian obligation is obviated if satisfying it would involve a violation of other duties. Individual patient rights cannot be violated. In circumstances where the design of a trial acknowledges these rights, medicine has a moral obligation to perform trials, and individual physicians have an obligation to support those trials. Medicine should not ignore its obligations despite the difficulty of performing clinical trials in elderly persons. Randomized controlled trials do not violate the requirements of a physician's exclusive commitment to a patient's well-being if the trials are properly designed. Physicians cannot ignore the history of these trials and the requirements for valid evidence. Geriatric research has a clear commission.