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.