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Clinicians are generally trained to consider outcomes from clinical trials as the gold standard for how to apply evidence-based medicine to clinical care. Ideally, clinical trials would include any patient who is a logical candidate for the therapy being examined. Unfortunately, most clinical trials include only idealized patients, excluding patients in whom the therapy has a greater risk of side effects, or patients who are at risk for not completing the trial. However, these nonidealized patients who are commonly excluded from clinical research are just the type of patients seen in geriatric practice, and in whom the therapies will often be used and marketed.
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Zulman et al have described a framework that outlines the reasons older persons may be excluded from clinical trials. These reasons include explicit age exclusions, implicit age exclusions, and unintentional age exclusions.
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Explicit Age Exclusions
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Many studies have age-specific cutoffs in which all subjects above a defined age are denied enrollment. Although these exclusions are common, they can almost never be justified. Most studies with explicit age exclusions present absolutely no rationale to justify the exclusion.
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An explicit age exclusion is only justifiable if one clearly would not offer a therapy in clinical practice to persons older than a particular age. In actual practice, most therapies tested in younger patients are eventually offered to older patients. Furthermore explicit age exclusions ignore the vast heterogeneity in health in older persons.
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Implicit Age Exclusions
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More often, the reasons for excluding older subjects are more subtle. Many studies without an age cutoff have exclusion criteria that differentially restrict the entry of older patients, particularly older patients who are more medically complex. Examples of implicit age exclusions include comorbidity, functional impairments, cognitive impairments, and inability to give informed consent.
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Treatment studies often focus on the effect of a specific treatment on health outcomes in persons with a specific condition. But most older people have multiple conditions. Yet many studies of specific conditions exclude patients with additional health conditions other than the condition being studied. For example, a study comparing the effectiveness of bronchodilator and anticholinergic inhalers for chronic obstructive pulmonary disease (COPD) excluded persons with chronic kidney disease or hospitalizations for congestive heart failure (CHF) in the past year. This is very problematic in older persons, as many older persons with COPD have coexisting chronic kidney disease or CHF. In actual practice, comorbidity is the norm, not the exception, and most treatments are still offered to older patients despite this comorbidity. It is difficult to judge the risk and benefits of treatments studied in idealized patients when applied to real patients with complex comorbidity.
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Functional Impairment
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Many studies exclude patients with “poor performance status” or poor functional status. Although there are many simple tools available to define functional status, often studies do not include a definition of poor functional status.
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Many older patients have functional limitations and, in practice, these are rarely viewed as contraindications for most therapies. Often, the goal of therapy for older adults may be to prevent further loss of function. However, functional problems, such as falls, can markedly alter the risk and benefits of therapies. The failure to account for functional impairments in most studies makes it difficult to gauge how a patient’s functional impairments should affect the decision to offer a treatment.
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Cognitive Impairment and Inability to Consent
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Studies often exclude subjects who have cognitive impairment or are unable to provide informed consent. Often, the studies fail to describe how cognitive impairment or consent capacity was assessed.
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Cognitive impairment is extremely common in older patients and older adults with cognitive impairment are usually offered the same therapies as patients without cognitive impairment. Because most studies fail to even describe the cognitive status of their subjects, it is often impossible to know how cognitive impairment might impact the risks and benefits of a treatment. Additionally, in clinical practice, family members are often asked to consent to treatments when the patient is unable to fully understand the risks and benefits. While methods exist for enrolling these patients in studies using similar approaches for surrogate consent, surrogate consent is often not attempted.
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Nursing Home Patients
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Virtually all treatments offered in the community are offered to persons in nursing homes. It is extraordinarily rare to find a study of any therapy that even considers nursing home patients as candidates for enrollment. As a result, there is an extraordinary lack of evidence to guide most therapeutic decisions in nursing home patients.
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Unintentional Exclusions
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Even when studies have few exclusion criteria, study processes may unintentionally exclude older patients who are potential targets for therapy. For example, many studies have complex procedures for follow-up. Often follow-up procedures require patients to report to a study center for examinations and blood draws. But many older patients no longer drive, making participation difficult. This type of subtle exclusion is important because the same factors that make study follow-up difficult may make the type of monitoring and followup that is needed difficult in the less mobile older patient being considered for treatment. Also, while sensory problems, such as vision and hearing impairment, may not be an explicit study exclusion, sensory impairment may make study enrollment and follow-up difficult for older patients. For example, older adults with hearing impairment may be excluded from studies that screen enrollees over the phone or require answers to phone-based health status questionnaires. Many studies do not budget the extra cost needed for in-person interviews for older participants who are hard of hearing.