New study provides guidelines for conducting paediatric obesity pharmacotherapy clinical trials
A new paper published in our journal 'Pediatric Obesity' presents critical considerations for the design and conduct of clinical trials involving medications to treat obesity in children and adolescents.
The study, a collaboration between North American and European experts, offers valuable guidance on how to streamline and improve the safety and efficacy of these trials, addressing the unique challenges posed by growth and development in young participants.
With the rising prevalence of childhood obesity, anti-obesity medications have emerged as a promising treatment option. However, conducting clinical trials in the paediatric population presents numerous challenges, from ethical considerations to ensuring long-term safety. The study, led by Dr. Aaron S. Kelly and a multidisciplinary group of paediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry, aimed to create a consensus on the best practices for running these trials.
Key recommendations for trial design
One of the most significant outcomes of the expert roundtable meetings, held in conjunction with ObesityWeek® 2022 and the European Congress on Obesity 2023, was a call for moving away from using Body Mass Index (BMI) z-score as a primary endpoint in clinical trials. The ideal primary endpoint would be a measure of body fat but it was acknowledged that practical considerations limit their widespread use. So, experts recommended shifting towards other BMI-related metrics for now and incorporating body fat measurements as secondary endpoints. These changes would provide a more accurate picture of treatment effects, especially in cases of severe obesity where traditional BMI measurements may not reflect true adiposity.
The roundtable also provided guidance on selecting trial participants. The experts stressed the importance of broadening eligibility criteria to include diverse populations, such as children with mental health conditions and those from historically marginalised groups. This inclusivity will improve the generalisability of trial results and better reflect real-world clinical settings.
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Ethical considerations and follow-up phases
One of the most debated aspects of paediatric obesity trials is the use of placebo-controlled designs. While these trials are considered the gold standard for determining efficacy, the experts noted the potential risks of using placebos, especially given the progressive nature of obesity. Although participants in the placebo group often receive lifestyle therapy, there is concern that withholding medication could lead to worsening obesity in some individuals. To mitigate this risk, the experts recommended limiting placebo use and ensuring that trial protocols include options for rescue medications or study withdrawal in the case of substantial weight gain.
The study also highlighted concerns about follow-up phases after discontinuation of AOMs. Given that weight regain is a hallmark of untreated obesity, the panel advised against extended follow-up phases without access to active treatment, which could potentially harm participants both physically and psychologically. Instead, they suggested exploring alternatives such as open-label extensions, which would allow for ongoing monitoring while maintaining treatment access.
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Long-term impact and future directions
This paper serves as a comprehensive guideline for researchers, industry representatives, and regulatory bodies involved in paediatric obesity pharmacotherapy trials. By addressing issues such as eligibility criteria, ethical considerations, and appropriate endpoints, the authors hope to streamline the clinical trial process, making it more efficient and ethically sound.
The recommendations also emphasise the need for future research to develop better methods for measuring body fat and adiposity in children, as well as the importance of patient-reported outcomes, particularly in terms of quality of life and mental health. World Obesity are supportive of these recommendations and also call for greater inclusion of globally representative stakeholders in future roundtables on this topic. These insights are crucial for the development of more effective treatments for paediatric obesity, a condition that continues to affect millions of children worldwide.
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World Obesity publishes four scientific, peer-reviewed journals, each focusing on a different area of obesity research: systematic reviews, pediatrics, clinical treatment, and science and practice.
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