Introduction
Clinical drug trials play a critical role in developing effective and safe therapeutic interventions and treatments. As the world’s population ages, frailty is becoming an increasingly important, particularly in clinical practice and medical research. There is an urgent need to narrow the evidence practice gap in the treatment of older frail people. The projected global growth of older adults underwrites the need to have greater evidence on how to use medications safely and effectively in this vulnerable group. Although the interest in clinical trials involving frail older patients is increasing, there has been a large evidence gap for such people due to intended (and unintended) exclusion from clinical trials.1,2 Ageing and frailty are associated with many physiological changes such as increased body fat, reduced lean body mass and serum albumin, decreased liver function and reduced renal clearance.3 Older people, especially the frail, usually have increased sensitivity to many drugs due to changes in body compositions and organ functions that lead to altered drug absorption, distribution, metabolism and excretion.4,5Frailty, defined as a state of increased vulnerability and reduced physiological reserve, carries an increased risk of poor outcomes in older adults.6 Clinical drug trials have traditionally focused on younger, healthier participants with less comorbidities who would be able to tolerate the medications and excluded frail older adults due to concerns regarding their ability to tolerate and respond to treatments. However, with the ageing population and a change in attitudes to older people (less ageism) frailty, , has become an increasing issue for drug trials. This has led to a growing recognition in recent years of the importance of including frail older adults in clinical drug trials. Over the past decades, increasing efforts have been made to include frailty assessment and to examine responses to drug effects according to baseline frailty in some randomised controlled trials.
The aim of this narrative review is to provide an overview of how frailty was assessed in published studies related to clinical pharmacological trials, and on the interaction of frailty on the safety and efficacy of the treatments.