Need for Redesigning Pharmacologic Research in Older Individuals. A Position Statement of the Geriatric Working Group of the Agenzia Italiana del Farmaco (AIFA)

Abstract

66 Discussions about the most appropriate methods for testing the effectiveness and safety of pharmacological intervention for older patients crowded the literature of the past decade, but little action has followed from such a wide discussion. The number of patients aged 65 years and older included in randomized controlled trials raised. However, epidemiological studies have generally demonstrated that the phenotypic emergence of the negative consequences of aging occur much later in life, in the eighth and ninth decade. Interestingly, this is the section of the population that is experiencing a steep demographic expansion, is often affected by severe comorbidity and disability, is the most eager consumer of drugs, and also the most likely to suffer from the iatrogenic consequences of chronic treatment and polypharmacy (1). In the United States, nearly 90% of patients over 75 years of age receive one or more medications, and the probability of having multiple prescription increases geometrically with age, severity of illness, and poor physical and cognitive function (2). There are many reasons why frail older persons that assume multiple drugs are prone to develop iatrogenesis, including drug–drug interactions, reduced physiological reserve, changes in pharmacokinetics, and poor compliance (3). The management of comorbid conditions with multiple medications is indeed one of the greatest challenges in geriatrics. The Hippocratic oath “primum non nocere” is translated into the “unchallenged principle” in geriatric medicine: The number of medications should be kept as low as possible. However, when facing the “brown bag full of pills” brought by your patient, deciding which treatment can stay and which one should go is challenging. Of course, only drugs with proven efficacy should stay, but this is also not an easy decision. Elderly patients with comorbidity, disability, and polypharmacy are systematically excluded from clinical trials, even those trials that test drugs mostly used in those same elderly patients with comorbidity, disability, and polypharmacy. Due to those exclusion criteria, the findings of these trials cannot be extended to our typical patients: Therefore, we are left with an “unchallenged principle” and impossible decisions (4,5). We are certainly not the first to denounce this difficult situation. Eminent geriatricians have voiced that the current practice produces an evidence-biased rather and evidencebased medicine and have called for the conduction of appropriately designed trials involving real geriatric patients (6,7). Letter to the Editor