Retaining Adolescents in Long-Duration Obesity Trials

Pivotal anti-obesity medication (AOM) programs now routinely run 52 to 72 weeks or longer. For example, STEP TEENS assessed semaglutide over 68 weeks in adolescents 12 to <18 years, and the FDA’s 2025 obesity guidance anchors the primary efficacy parameter to sustained change over at least a year.^1,2 Although these durations are scientifically defensible, they are also long enough to span full school years, place a participant through multiple rounds of puberty-linked growth change, and expose them to sustained peer observation. As a result, retention strategies derived from adult AOM trials may not be broadly applicable to adolescents and require development around the unique needs of the population.   

A Different Discontinuation Signature 

In adult AOM trials, attrition is predominantly driven by tolerability and perceived efficacy, with GI-related dropout in the 4-7% range in SURMOUNT-1, and broader Phase 3 attrition of 15-30% across the STEP and SURMOUNT programs.^3,1 In STEP TEENS, gastrointestinal adverse events were reported in 62% of participants receiving semaglutide and 42% receiving placebo, while adverse events led to treatment discontinuation in 5% and 4%, respectively. Treatment completion was 90% in both groups, whereas trial completion reached 99% with semaglutide and 96% with placebo. Participants who stopped treatment were asked to attend the remaining trial visits. These results highlight an important distinction: stopping investigational treatment does not necessarily mean withdrawing from the trial. ¹  

Retention planning should include adolescents who discontinue investigational treatment. At enrolment, participants and families should understand that stopping treatment and stopping study participation are separate decisions. If they agree to continued follow-up, sites should explain which visits and assessments remain, why those data matter, and what support is available. Conversations should make clear that stopping treatment is not a personal failure and that continued participation remains valuable. Protocols and site workflows should support collection of the remaining safety and outcome assessments, where appropriate and with the participant’s agreement. 

The Visible Placebo Disadvantage 

Weight bias internalization (WBI), or the degree to which an adolescent applies negative weight-based stereotypes to themselves, is already elevated among adolescents who present for weight management treatment, with peer-based weight victimization reported by as many as 90% of this group and family-based victimization by 60%.⁴ Furthermore, a placebo participant who is not losing weight in a long duration trial experiences this in a public setting, actively comparing against classmates, teammates, and a treatment arm that may be visibly changing.  

It has also been found that pubertal stage and dropout are correlated directly. A 24-month cohort of 489 pediatric weight-management patients found a 60.7% dropout rate, with dropout probability rising with pubertal stage.5 A separate cohort of 183 pubertal adolescents found the greatest dropout risk in participants older than 15 and those with elevated eating-disorder symptomatology (OR 0.40 and 0.35, respectively, for adherence).⁶ 

The School Calendar as a Structural Barrier 

As initially described, adolescent AOM trials can span multiple academic terms, exam periods, holidays, and extracurricular seasons. Visit frequencies designed around the adult convention coincide with and disrupt these periods. However, planning around the school calendar remains an unmet need in adolescent AOM trials.  

A cross-sectional survey of the Children's Oncology Group's AYA Research Investigator Network found administrative and logistical issues, such as disruption of the school calendar, to be the single most cited barrier to enrolling and retaining adolescents and young adults in clinical trials (45% of respondents), ahead of communication issues between care teams (27%) or perceived limited trial availability (27%).^7,8   

Disclosure Anxiety 

Given how prevalent weight-based victimization already is in this population, an absence from class or practice that prompts a peer or coach to ask why carries a different impact than it would for an adult. For a condition still burdened by stigma, fielding that question repeatedly over more than a year of trial participation is itself a retention risk that has no adult analogue and is largely undocumented in AOM-specific retention literature to date. 

Grounding Adolescent-Specific Findings in the Broader Pediatric Evidence Base 

The three developmentally specific components described above sit on top of the general pediatric evidence base. A 2025 PRISMA-guided scoping review of 31 studies conducted between 2009 and 2022 described effective pediatric enrolment and retention strategies into a layered model, focusing on building trust, providing effective and sufficient incentives, and incorporating continuous feedback.⁹ Several of these strategies validated in the broader model transfer directly into AOM trials, while others reveal where AOM-specific risk adds a caveat not currently addressed:  

Flexible Scheduling and Electronic Tracking Transfer Directly 

Flexible scheduling, including after-hours slots, weekend visits, and rescheduling on request, as well as deployment of automated, multi-modal reminders were both identified as effective retention levels across the general pediatric literature, with one cited study reporting retention as high as 88% after combining accessible visit locations, frequent reminders, and timely incentive payments.⁹ These generalize into the AOM context, where the school-calendar-aware scheduling gap is understood as this same principle.  

A retention plan needs to work for both the adolescent and the person helping them attend visits. Sites should agree with the adolescent and caregiver on preferred contact methods, reminder recipients, transport arrangements, and who can help when schedules change. These arrangements should be reviewed during the study as adolescents become more independent and family circumstances change.

Reimbursement and incentives should recognize participation 

Reimbursement and any approved incentives should recognize participants’ time, effort, and study activities rather than weight loss or treatment response. Payments should be clearly explained, proportionate, and structured so that participants can withdraw without losing compensation already earned. The pediatric scoping review identifies incentives as one component of a multifaceted recruitment and retention approach, rather than establishing a single payment structure as the most effective.⁹ 

Trust-Building Has to Extend Further in an AOM Context 

Language-concordant, culturally competent staff and continuity with a single, trusted provider were the most heavily weighted layer in the general framework, foundational to every other retention strategy built on top of it.9 In an AOM trial, trust has to hold across a stigmatized condition and a body-focused, comparison-rich endpoint.  

Retention plans should include brief opportunities for adolescents and caregivers to explain what is becoming difficult. A missed assessment may reflect a timetable conflict, a technical problem, discomfort with a question, or frustration with the study. Asking directly allows the site to respond to the actual problem rather than simply send more reminders. Feedback should be reviewed regularly and used to make feasible adjustments within the protocol. 

Where the General Model Is Silent 

The general pediatric retention framework does not address peer-visible outcome exposure, puberty-linked physiological change, or school-calendar-aware scheduling logic. Consequently, 52-to-72-week adolescent AOM trials require the additional adolescent-specific components applied alongside the foundational framework.  

Gamification: What the Evidence Supports, and Where the Guardrails Belong 

A 2025 scoping review conducted using PRISMA-ScR identified 15 studies of gamified eHealth interventions in children and adolescents. Eighty percent reported improvements in health-related knowledge, motivation, or attitudes, while only 40% reported an underpinning theoretical model. Game evaluation, conflict/challenge, and rules/goals were present in all studies analysed.¹⁰ 

Gamified approaches may support engagement, but their effect on retention in long-duration adolescent AOM trials remains to be established. Private, participant-paced activities linked to study participation are a reasonable design option. Public rankings and rewards tied to weight change warrant caution in a population where comparison and weight stigma may already affect wellbeing. 

Signant’s analysis of 24 goal-setting RCTs published between 2016 and 2025, involving more than 5,000 participants, found greater Goal Attainment Scale improvement with dietary and behavioural goals (71%) than with weight-loss goals (39%).¹¹ These findings support considering behaviour-focused goals, while assessing goal attainment and trial retention as separate outcomes. 

Where This Leaves Trial Sponsors 

Long-duration adolescent AOM trials need retention plans that account for school commitments, family logistics, treatment expectations, tolerability, and the social experience of weight management. STEP TEENS shows that high trial completion is achievable, including when some participants discontinue treatment.¹ Broader pediatric research identifies flexible scheduling, practical assistance, trusted site relationships, and regular feedback as relevant approaches, although the contribution of individual strategies remains difficult to isolate.⁹ 

For sponsors, the priority is to make participation manageable and worthwhile throughout the study. That includes supporting follow-up after treatment stops, responding to emerging burdens, and avoiding engagement activities that turn weight change into another source of comparison.  

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About the authors

	Lauren Crooks, MSc has comprehensive cross-functional experience within the life sciences and information technology sectors. At Signant, she combines this experience to provide scientific consultation and support to clients on the implementation of eCOA to optimize patient care and outcomes in clinical trials. She has supported eCOA projects across multiple therapeutic areas, including dermatology and neurology, with a current focus on respiratory diseases.
	Marcela Roy, MA, ACC serves as Executive Director of Clinical Science & Medicine, bringing over 20 years of clinical and research expertise to her role. She provides strategic leadership across CNS and non-CNS therapeutic areas, with particular expertise in psychedelic research and central ratings data quality monitoring methodologies.
	Elias Ketiar, MD, MRCP serves as the Clinical Vice President, Science & Medicine, at Signant Health. Dr. Ketiar draws on his wealth of more than 20 years of academic and clinical experience to advise on clinical trial design, execution, and governance. He has extensive experience in General Internal Medicine and Cardiology and is a Member of Royal College of Physicians (London), UK. Dr Ketiar has been engaged in academic research and was involved in a pioneering project investigating genetic causes of congenital heart disease, which culminated in a Medical Doctorate with St George’s University of London, UK. He also has peer reviewed papers published. He has always been involved in all phases of clinical development and interested in global clinical trial solutions.