What Really Drives Recruitment, Enrollment, And Retention — According To A PI
A conversation with Luke Twelves, MA (Oxford), MB, BChir (Cambridge), MRCGP (London), PGDipBA (Durham)
There’s no silver bullet. No magical solution. And certainly no cure-all, when it comes to patient recruitment, enrollment, and retention in clinical trials.
But critical incremental actions and decisions before and during a clinical trial can improve all three.
In this Q&A, principal investigator Dr. Luke Twelves details some of his most trying and most satisfying recruitment experiences, sharing very specific ways in which he and site staff positively impacted the patient experience and trial conduct.
Clinical Leader: Reflecting on recruitment and enrollment, which trials have been the most challenging? How about the easiest? And what allowed you to meet enrollment numbers?
Dr. Luke Twelves: Every study presents its own set of challenges, but over time, I’ve noticed recurring themes — especially around population size, accessibility, short recruitment windows, and overall trial appeal. Looking back, four experiences in particular stand out as especially difficult to recruit for.
One of the most complex studies I’ve worked on involved patients with hidradenitis suppurativa. While the condition itself isn’t rare, we needed patients experiencing a specific severity level during active flares, which narrowed our target population considerably. Traditional dermatology clinics estimated only one or two eligible patients per site per month — nowhere near what we needed to hit our timelines. I found that incredibly frustrating. To solve it, we shifted to a very different approach: using EHR searches combined with remote screening through qualification calls and tele dermatology. That strategy led to recruitment rates being nearly 10 times higher than the standard site-based model. It also gave us valuable data on how nontraditional methods can outperform passive recruitment in the right context.
Another trial that proved difficult was a home diagnostic study with an STI testing sub-study. The main study recruited well, but the sub-study required recently diagnosed STI patients — ideally pretreatment or within a very tight post-treatment window. Waiting for patients to present on their own wasn’t going to cut it. We had to move quickly, combining social media outreach with partnerships at sexual health clinics and building rapid logistics for home kit delivery. What I learned there is that recruitment strategies need to be as fast and flexible as the disease itself — a principle I’ve applied to other time-sensitive studies, like those involving acute flare-ups or early-stage infections.
I’ve also run into recurring problems with overly optimistic site feasibility assessments. I’ve seen what happens when projections are taken at face value — you end up scrambling when numbers fall short. But I’ve also seen the downsides of blanket skepticism, which can damage site relationships and inflate costs. I’ve learned that the key is early investment in accurate, evidence-based assessments. I work with sites to run detailed EHR queries that reflect actual inclusion and exclusion criteria, and I have open, probing conversations with them about what’s realistic. These conversations, though sometimes uncomfortable, help build stronger partnerships based on trust and shared understanding. I also prefer phased recruitment, so we can scale site activation based on performance instead of initial projections.
Another challenge I’ve faced is ensuring that trial populations reflect the diversity of the real-world patients we’re trying to serve. Too often, traditional sites enroll older, wealthier, and less diverse participants, which limits generalizability. I’ve tried to address this in two ways: by partnering with community-based sites that serve underrepresented populations and by implementing decentralized recruitment strategies supported by dedicated diversity teams. These teams focus on culturally tailored outreach through local organizations and multilingual digital campaigns. It’s a continuous effort, but one that’s absolutely necessary if we want our research to reflect reality.
Across all these experiences, one thing has made a big difference: making sure the recruitment strategy is aligned with trial success, not just operational output. I’ve found that when success is defined by meeting timelines and enrolling the right patients, not billable hours, the entire approach shifts. I now go into every trial with that mindset — as a problem-solver first. And that shift has changed how I design and execute recruitment strategies entirely.
Generally, what approaches do you deploy to drive recruitment and enrollment?
I often rely on EHR-based recruitment strategies that use algorithmic searches to identify patients who are most likely to meet a trial’s eligibility criteria. These searches go beyond standard criteria to account for how clinicians actually document information — using real-world coding patterns, proxy terms, and common synonyms. For example, we’ve had more success searching for “low libido” instead of “reduced sexual desire,” because that’s how it’s more commonly recorded in GP systems.
I also prioritize embedding outreach within patients’ existing care settings. When trial invitations come directly from a patient’s clinic or physician — rather than an unfamiliar research team — they’re far more likely to engage. That sense of trust and familiarity makes a measurable difference.
These approaches aren’t static. I pilot them with clinical partners and refine the search protocols based on feedback to improve accuracy and performance over time.
Once patients are enrolled, what do you believe keeps them engaged and retained in the trial?
Retention strategies must be tailored to specific trial populations and requirements. What works for one study – weekend visits or evening visits, for instance – might be completely inappropriate for another, where home nursing visits are more suitable. However, I've observed several core principles that consistently drive retention success across different study types.
The most important factor is the relationship between participants and the research team, especially through dedicated patient coordinators. These individuals act as advocates — not just schedulers — and need to be trained in protocol details so they can answer questions, anticipate concerns, and help participants navigate the process. When patients feel known, supported, and understood, they’re far more likely to stay engaged. Perceived value is equally important, and this works on two levels. Participants need a clear understanding of both potential personal benefits and their broader scientific contribution. This dual motivation — helping themselves while contributing to future advances — has always been powerful, especially in oncology trials. But I’ve seen it resonate just as strongly in under-researched areas, where patients feel they’re contributing to something that hasn’t been studied enough and matters deeply to them. The operational aspects also need to be considered. For example, convenience, flexible scheduling, reasonable visit frequency, and minimizing travel all have a major impact on retention. In my experience, even small accommodations — such as offering visits outside traditional hours or reducing the number of in-person appointments — can make a big difference in keeping participants committed through the full duration of the study.
What approaches or tools have you used — initiated by the site or by the sponsor — to help retain them? Which worked and which didn’t?
I’ve found that simple, participant-friendly digital tools can have a big impact on retention — especially when they’re designed to be low-burden. One approach that’s worked well is using secure single-use survey links that participants can access directly from their email or text message, without needing to download an app or remember a password. These systems typically work across all devices — phones, tablets, and computers — which makes participation easier, particularly for those who may not be tech-savvy or don’t have consistent access to one type of device. In addition to technology, adequate financial support is critical, especially in studies involving lower-income populations. I've seen participants genuinely want to stay in a trial but have to cancel visits because they can't afford to miss work. In those cases, the issue isn’t motivation — it’s logistics. Fair compensation helps remove those barriers and supports continued engagement. Another key factor is how well the site supports participants throughout the study. I’ve worked with teams that prioritize ongoing communication, education, and problem-solving, often through a dedicated coordinator. That personal connection goes a long way. When participants know there’s someone they can reach out to — someone who knows the protocol and understands their circumstances — it builds trust and commitment.
What changes would you like to see in the realm of patient recruitment, enrollment, and retention?
One of the biggest opportunities for transformation lies in better integration between EHR systems and clinical trial platforms. We currently spend enormous amounts of time on manual patient identification processes that should be automated. AI-powered systems that can seamlessly match patients to appropriate trials based on their medical history — and real-time clinical status — would revolutionize how we approach recruitment efficiency and accuracy.
I also think regulatory flexibility represents another significant opportunity for improvement. Risk-based monitoring approaches that allow flexible visit windows, remote data collection for low-risk assessments, and streamlined protocol amendments would dramatically improve our ability to adapt trials based on what’s actually working for patients. Current regulatory systems are often too rigid or slow to respond when we identify strategies that work better for patients mid-study. This means we sometimes have to continue with suboptimal approaches simply because the amendment process is too cumbersome.
When it comes to diversity, we desperately need standardized approaches to community engagement and culturally competent research practices that are built into study design from inception — rather than treated as afterthoughts. Community engagement and culturally competent research practices should be baked into study design from the start. When diversity efforts are reactive, they’re often less effective — and they can feel more like a checkbox than meaningful inclusion. Perhaps the most fundamental change I’d like to see is a shift in public understanding of clinical research. Too often, clinical trials are seen as risky or intimidating — something done to people, not with them. We need to do a better job — across media, policy, and industry — of communicating the value of research as a public good. Clinical trials are an opportunity: a way to access cutting-edge care while contributing to progress. If we can change that perception, we can improve participation, reduce recruitment costs, and ultimately bring new treatments to market faster and more equitably.
In the end, successful trials require a shift away from passive transactional recruitment models toward approaches that center the participant experience. That means prioritizing accessibility, meaningful engagement, and representative populations, supported by thoughtful use of technology, strong community partnerships, and aligned incentives across sponsors, CROs, and sites. A key part of this transformation is aligning incentives across sites, CROs, and sponsors around overall trial success — not billable hours or enrollment quotas. When all stakeholders are working toward the same goal, collaboration becomes more authentic and solutions are more effective. The strongest recruitment and retention strategies emerge when participants’ needs shape trial design, supported by realistic feasibility assessments and flexible, responsive operational models that reflect real-world patient experiences.
About The Expert:
Luke Twelves, MA (Oxon), MB BChir (Camb), MRCGP (Lond), PGDipBA (Durh), is a general practitioner as well as VP of Medical at Lindus Health, where he combines strategic and operational initiatives. Previously, Dr. Twelves was the CEO of a healthcare provider providing dermatology, ENT, diagnostic, and general practice services to the National Health Service (NHS) in England.