American College of Clinical Pharmacology has issued a Position Paper calling for actions to enable the inclusion of people with obesity in clinical trials during the drug development process. Inclusion of these participants in clinical trials during drug development should be considered and discussed among clinicians, sponsors and regulators in the context of the prevalence of obesity and related comorbidities in the target patient population, the paper states.
Potential impact of obesity on the clinical pharmacology of drugs, current dosing paradigms in patients with obesity, clinical pharmacology tools to evaluate impact of obesity on dosing, and regulatory considerations are discussed in the paper. The paper proposes a road map for the inclusion of patients with obesity within clinical trials and evidence synthesis through model-informed data integration to optimise the posology of therapeutics and maximise benefit versus risk in the intended patient population.
American College of Clinical Pharmacology has issued a Position Paper calling for actions to enable the inclusion of people with obesity in clinical trials during the drug development process. Inclusion of these participants in clinical trials during drug development should be considered and discussed among clinicians, sponsors and regulators in the context of the prevalence of obesity and related comorbidities in the target patient population, the paper states.
Potential impact of obesity on the clinical pharmacology of drugs, current dosing paradigms in patients with obesity, clinical pharmacology tools to evaluate impact of obesity on dosing, and regulatory considerations are discussed in the paper.
The ACCP proposes the following roadmap (Figure 1) to include these patients participants within clinical trials with the consideration of disease epidemiology, comorbidities, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of the investigational agent, and encourages evidence synthesis through model-informed data integration to optimize the posology of therapeutics and maximize benefit versus risk in the intended patient population:
Learn and characterize the effect of obesity on the PK, PD, efficacy, and safety of drugs through all phases of the clinical development program, leveraging applicable MIDD tools.
Expand the inclusion and exclusion criteria of clinical studies to enable inclusion of obese participants when data are available to support doing so safely.
Include dosing information in relation to body size descriptors in drug labels when appropriate to guide their safe use in obese patients.
Currently, typical trial designs fail to appreciate that there can be important differences in the distribution of body size/weight/BMI in the actual target patient population assessed later during clinical development. Moreover, despite the overall steadily increasing prevalence of obesity in the US population, dosing recommendations for obese patients are typically not provided in the majority of the current FDA-approved labels.
“Therefore, other alternative methods using body size descriptors such as adjusted body weight, lean body weight, and ideal body weight, which rely on physical attributes of individuals such as height, weight, sex, and, more importantly, body proportions, may be needed to guide dosing in these individuals,” the paper states.
The Position Paper, ‘Inclusion of Obese Participants in Drug Development: Reflections on the Current Landscape and a Call for Action’, was published in The Journal of Clinical Pharmacology. To access this paper, please click here