Cardiometabolic Trials are Exposing a Flaw in the Clinical Research Model: Retention is Engineered Upstream
Across clinical research, recruitment, for obvious reasons, dominates the conversation. Timelines, feasibility, site activation. All framed around how quickly participants can be identified and enrolled.
But recruitment is rarely what breaks a study. Retention is.
In many long-duration trials, dropout rates of 30–40% are not uncommon, with higher attrition observed in complex or behaviourally influenced conditions.
And yet, despite its impact on timelines, cost, and data integrity, retention is still often treated as a downstream operational challenge. Something to be managed by sites once a study is underway.
This framing is increasingly difficult to sustain. Because by the time a participant drops out, the cause is rarely new. It was built into the study from the start.
Why cardiometabolic trials expose the problem
Cardiometabolic studies operate under conditions that expose weaknesses in the traditional model.
They are behaviourally influenced, with outcomes shaped not only by pharmacology but by diet, physical activity, and adherence, and the broader treatment landscape individuals are already navigating in routine care. All factors that fluctuate over time and are closely tied to daily life[i].
They are embedded in the realities of everyday life. These are chronic conditions that individuals manage continuously, often alongside work, caregiving responsibilities, and other health needs. As a result, participation in research must be sustained within the context of routines, rather than accommodated as a short-term intervention.
This is reflected in the evidence. Studies in diabetes and cardiovascular disease have consistently shown that longer trial duration and higher participant burden, often driven by protocol decisions around visit frequency, site location, and in-person requirements, are associated with increased dropout rates, while adherence is strongly influenced by behavioural and social factors[ii]. Similarly, in obesity trials, discontinuation rates for GLP-1 therapies are driven not only by clinical factors such as gastrointestinal side effects, but by the practical and behavioural realities of sustained treatment[iii].
Participants are not stepping briefly into a study. They are incorporating it into routines and competing priorities. In this context, participation is not a single decision. It is a sustained commitment.
The limits of the model
Despite acknowledgement of these issues, the industry continues to operate on an episodic model of engagement.
Participants are identified, screened, enrolled, and then expected to adhere to a defined protocol over time. Engagement is concentrated around study visits. Communication is structured, scheduled, and often minimal between those points.
That model assumes:
- participants can adapt their lives to the study
- motivation is stable
- engagement can begin at recruitment
In practice, these assumptions do not consistently hold.
Engagement that starts at screening starts too late.
Participants are asked to commit at the same moment they are first introduced to research. There is no prior familiarity, no established trust, and no context for the decision.
At the same time, many trials continue to rely on site models that are not aligned with how people access healthcare in their daily lives, often centred around hospitals or specialist centres, rather than convenient, familiar and trusted care settings
The result is predictable. Structural misalignment between how trials are delivered and how participants live. And sites are left to manage the consequences and solve problems they did not create.
Site execution remains critical. But sites are often operating within constraints defined earlier, in protocol design, feasibility assumptions, and delivery models.
What actually drives dropout
The drivers of dropout are well understood.
- Visit burden accumulates
- Logistics compound
- Side effects go unmanaged
- Perceived value declines.
And when examined more closely, the underlying drivers are consistent and, importantly, predictable.
- Visit burden is a primary factor. Frequent appointments, travel requirements, and time commitments accumulate over time, particularly in long-duration studies.
- Life logistics play an equally significant role. Work schedules, childcare, transportation, and competing health priorities introduce friction that compounds with each visit.
- Clinical factors also contribute. In obesity and diabetes studies, gastrointestinal side effects are well documented and often peak early, yet are not always proactively managediii.
- Perceived value matters. Participants who do not feel a clear benefit from continued participation are more likely to disengage.
For a participant, this rarely feels like a single barrier. It is the midweek appointment that requires time off work. The repeated travel to a site that is not locally accessible. The side effects that are expected but not fully understood. Individually manageable. Collectively enough to disengage.
None of these factors are unexpected. None are unique to individual participants.
Dropout is rarely a moment. It is a process. And because it is a process, it can be anticipated.
In practice, where participants have an existing relationship with a site, and a clearer understanding of both their health and the role of research, these points of friction are often easier to identify and address earlier, before disengagement occurs.
Retention friction does not sit only with participants. Site burden matters too. Fragmented systems, duplicated workflows, and the operational strain of managing retention reactively reduce the time and attention sites can devote to participant support. In that sense, participant retention and site experience are not separate issues. They are part of the same design problem[iv].
These factors are not independent. They are the direct consequence of how trials are designed, shaping participant experience, which in turn determines whether individuals remain engaged or disengage over time.
What needs to change
The implication is not that sites need to do more. It is that the system needs to change what it asks of them.
- Retention needs to be considered prior to feasibility, not after enrolment.
- Trial design needs to reflect how people actually live – from visit schedules and site location to how frequently participants are asked to attend in person.
- Engagement needs to begin before recruitment windows open.
Support must also reflect the reality that participants experience a study continuously, not just during scheduled visits.
This also means designing for sites, not just participants. Retention cannot depend on adding tasks, tools, or interventions once a study is live. If the underlying design increases operational burden, those efforts rarely compensate. Retention strategies that are participant-centric but operationally heavy are unlikely to hold[v].
Some site models are beginning to reflect this shift.
Community-based approaches extend access beyond traditional hospital settings and align research with how people already interact with healthcare. Models that incorporate ongoing screening, education, and interaction outside of active studies build familiarity with research over time.
This approach, engaging individuals earlier through screening, education, and ongoing interaction, creates a different starting point. Participants are not encountering research for the first time at consent. They are already informed, already engaged, and more able to participate within the context of their broader health journey.
This does not eliminate retention challenges. But it changes the starting point.
And where that starting point is designed deliberately, for both participant experience and site feasibility, retention becomes more predictable.
Looking ahead
Cardiometabolic trials are not an exception. They are a preview. As studies become longer, more complex, and more reflective of real-world conditions, the limitations of episodic, site-based models will become more visible. Retention will increasingly define study success, and it will not only be solved at site level, because the signal is already clear:
Retention is not an operational outcome. It is a design decision.
And until clinical trials are consistently designed around the realities of participants’ lives, the gap between recruitment and retention will remain, not because sites are underperforming, but because the system has not yet adapted.
Civia Health is a clinical research site network designed to move beyond traditional, episodic recruitment models. Its approach focuses on engaging individuals earlier in their health journey through screening, education and ongoing interaction, with the aim of improving participant experience, retention and overall trial delivery. This perspective reflects this approach and is authored by Mark Campbell, CEO.
Sources:
[i] Polonsky WH, Henry RR. Poor medication adherence in type 2 diabetes. Patient Preference and Adherence. 2016.
[ii] Gul RB, Ali PA. Recruitment and retention challenges in clinical trials. Journal of Clinical Nursing. 2010
[iii] Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine. 2021.
[iv] Poongothai S et al. Participant-centric retention strategies in long-term trials. Perspectives in Clinical Research. 2023.
[v] Van Ooik K, Hutton M. Retention by design. Applied Clinical Trials. 2024.
