Clinical Insights 10 min read

Rethinking Recruitment and Retention in Competitive Oncology Clinical Trials

By Claudio Hegenberger, MD and Johannes Wolff, MD, PhD

In the current pharmaceutical environment, where the industry faces a potential patent cliff ranging anywhere from $236-400B in revenue,1,2 sponsors are under mounting pressure to hit increasingly aggressive milestones. Yet many programs underestimate the operational realities that shape recruitment and retention, particularly in competitive therapeutic areas like oncology or rare diseases. A growing body of research confirms this disconnect: nearly 80% of clinical trials fail to meet initial enrollment targets on schedule, and around 19% are terminated early due to insufficient accrual.3,4 Overall, only 40% of clinical trials reach their intended enrollment goals.5 Even when enrollment succeeds, retention presents a second major hurdle. It’s not unusual for dropout rates in trials to be as high as 25-30%,6 compromising both data integrity and statistical power. In long-term trials, these rates can rise even higher, especially when patients perceive limited therapeutic benefits.

In short, patient recruitment and retention represent major operational risks to successful oncology study completion generally, and in particular, for complex and competitive therapeutic areas. Our experience confirms these trends, and more importantly, sheds light on their root causes and potential solutions.

The Hidden Cost of Over-Engineered Protocols

Trial success hinges not just on recruitment but also on retention. This is particularly true for trials that run six months or longer. We’ve seen firsthand that when faced with the prospect of extended study periods, patients (and sometimes even their physicians) tend to opt out.

Many enrollment failures stem from protocol design choices that ignore operational feasibility. Two key culprits: overly narrow eligibility criteria and overly burdensome procedures. Sometimes there simply are no patients who meet study criteria, while in other instances, patients decline to enroll because the study is too disruptive to their lives.

Sponsors often pursue idealized patient profiles in an effort to reduce variability or optimize data quality. But this can backfire. High screen failure rates delay enrollment and inflate costs. Worse, once a study launches and fails to recruit, the sponsor must initiate protocol amendments, requiring re-approval by IRBs or ethics committees across multiple regions. This process often delays studies for weeks or even months.

KOLs and Monitors Matter

From our experience, we know that the people behind the protocol matter. Both key opinion leaders (KOLs) and medical monitors with deep therapeutic area expertise can help ensure that designs are grounded in both clinical and operational reality. KOLs are also essential in building investigator enthusiasm. This is a factor that significantly influences recruitment but is often overlooked. Investigators need to believe the experimental treatment is good for patients. And they need to hear that convincingly from someone who speaks their language.

Unfortunately, some sponsors delegate early-stage discussions to partners without sufficient scientific depth in the given therapeutic area, which can undermine site trust. This is far more common than expected. We believe strongly that CROs and KOLs who understand both the science and the clinical landscape can bridge this gap and help align study goals with investigator expectations.

Rethinking Patient Access

Switching to a non-competing CRO rarely fixes recruitment shortfalls if everyone is drawing from the same limited site pool. That’s because the constraint typically is patient access, not vendor choice. Sponsors benefit by rethinking access models, such as expanding beyond the usual site networks through partnerships that broaden geography and reach. CROs with genuinely differentiated site relationships can help, but the goal is to widen patient channels, not just change logos.

Consider that many studies involve sites juggling upwards multiple active protocols in the same indication. In one example, a rare disease trial struggled to enroll even eight patients over three years, partly due to there being multiple sponsors competing for the same tiny population. In such scenarios, the sponsor must carefully weigh whether different CRO partners with undifferentiated patient access actually can deliver a new set of patients to further the study.

A Better Path Forward

To improve oncology trial execution, and increase the likelihood of meeting study endpoints, sponsors can take practical action, including:

Using patient access strategies that extend beyond the traditional site model:
In highly competitive or rare disease trials, sponsors do better when they go beyond the standard network. Traditional patient-information channels such as ClinicalTrials.gov (and international equivalents), hospital trial listings, patient-advocacy organizations (e.g., Leukemia & Lymphoma Society, American Cancer Society), and word-of-mouth in clinics and conferences, still matter. Sponsors and CROs should have targeted strategies for each. But many potential participants never walk through academic centers’ doors.

In highly competitive or rare disease trials, sponsors benefit when they go beyond the standard network. There are entire populations that remain untapped because they don’t walk through the doors of clinical trial research sites and academic medical centers. We’ve worked with large, structured healthcare systems and institutional networks that aren’t formal study sites but have robust patient data, consistent engagement, and exceptionally high retention. Access to these patient populations is conducted under strict adherence to privacy laws and regulations, including HIPAA and other applicable privacy regulations, with Institutional Review Board (IRB) oversight where required.

  • Engaging experienced clinical developers and KOLs early in protocol design:
    Protocol development should not be done in isolation by regulatory or medical affairs teams. Drug developers who understand trial operations and feasibility should have a voice in early planning, alongside KOLs who understand the investigator and patient mindset. Equally important, representatives from patient advocacy groups or patient organizations should be engaged early to ensure the trial design and informed consent process are aligned with the real-world patient experience. Their input is critical for validating that consent language is accessible and understandable, helping to address one of the most common reasons patients decline participation — simply not understanding what they are agreeing to. Incorporating this perspective, strengthens both patient trust and trial enrollment ability.

  • Incorporating feasibility into design decisions:
    Feasibility is the foundation of a viable clinical study. One of the most common mistakes sponsors make is designing protocols based on theoretical patient profiles that don’t exist in the real world. We often see protocols with overly restrictive inclusion and exclusion criteria (no prior treatments, organ-specific constraints, narrow lab windows) crafted in the hopes of clean data. But in practice, this narrows the pool so drastically that sites can’t find eligible patients. Then, when enrollment falters, the sponsor scrambles to amend the protocol, which triggers ethics reviews, IRB re-approvals, and months of delay. If you want to de-risk a trial, feasibility must inform design from day one. That means involving people with deep therapeutic expertise (i.e., expert drug developers, not just medical writers) who understand both the patient population and operational implications. It also means integrating site and KOL feedback early, because they’re the ones who know if the study is even executable. Because if the assumptions baked into the protocol are flawed, all the modeling in the world won’t save the trial.

  • Using strategic country selection as a lever:
    Sponsors shouldn’t default to countries based on precedent or vendor habit; geostrategy should be driven by patient reality and explicit criteria. Prioritize these considerations:
    • future approval needs: run meaningful portions of development where you’ll seek licensure (e.g., U.S. cohorts for a U.S. label);
    • country-specific experience: prior wins, operational familiarity, and investigator relationships;
    • epidemiology and population data: size of the addressable population using WHO and national sources;
    • local regulatory hurdles—for example, Germany’s BfArM requirements for radiation protection; and
    • costs—startup timelines, per-patient economics, and hidden overhead.

      Applying these filters often surfaces non-obvious regions (centralized health systems, national registries, underutilized institutional networks) where evaluable patients are concentrated. If sponsors account for global regulatory timelines up front and leverage proven in-country partners, these choices can materially shift feasibility in their favor.

  • Beyond traditional sites:
    By leveraging trusted care environments, including military health systems or large retail healthcare providers, studies can ethically gain access to highly compliant patients who otherwise wouldn’t be reached. Not only do they improve enrollment, but they also dramatically improve evaluability and follow-through, which is what sponsors ultimately need.

  • De-risking studies by reducing protocol complexity:
    Complex protocols are often recognized as one the most consistent threats to trial performance.7 Every additional procedure, visit, or exclusion criterion may seem justifiable on paper, but cumulatively, they create a burden that drives screen failures, site fatigue, and patient dropout. We’ve seen many overly engineered protocols that are scientifically elegant but operationally unworkable. If the goal is to increase the likelihood of success of the trial and preserve data quality, then complexity must be reined in early. Simplify where you can. Prioritize what truly matters. Because complexity, far from being neutral, actually compounds risk at every stage.

  • Considering competing studies in the feasibility process:
    The number of other competing studies is often vastly underestimated during protocol planning. For rare diseases, this has a significant impact on the available patient pool. Sponsors should insist on a thorough competitive landscape analysis before locking in their enrollment strategy. Waiting until trial launch to discover the same patient population is already overcommitted is too late. And unfortunately, it happens too often.

  • Prioritizing retention equally with recruitment:
    A recruited patient who drops out is not evaluable, and represents a significant cost in terms of money, time and opportunity. Sponsors need to consider what motivates a patient to remain in a trial, particularly if they face a long study timeline. Retention strategy must be built into the protocol, including frequency of visits, reimbursement policies, remote monitoring, and communication plans.

To improve oncology clinical trial execution and meet study endpoints with greater confidence, sponsors must move beyond traditional thinking. That means engaging experts early, grounding protocol design in operational feasibility, and leveraging untapped patient access channels. It also requires viewing complexity, competition, and retention not as isolated challenges, but as interconnected risks that must be managed from day one. Trials are not just scientific experiments. They are operational systems with real-world constraints. We have seen firsthand that the sponsors who succeed are those who treat design, recruitment, and retention as strategic levers for de-risking, not afterthoughts. With the right planning and the right partners, clinical trials can move faster and deliver higher-quality data.

Authors:

Claudio Hegenberger, MD is VP of Clinical Affairs at Emerald Clinical Trial. Dr. Hegenberger brings 27 years of global experience in all pharma Medical Affairs areas (Clinical Development and Operations, CROs’ supervision, PV, MI, Safety, and country/regional MDs supervision), most recently serving as VP of Medical Affairs at Pfizer. With an MD in Internal Medicine, he holds multiple advanced degrees and certifications—including from Georgetown University, Mount Sinai Hospital, and Harvard — and became an Associate Professor of Internal Medicine in 2 universities in Argentina. Dr. Hegenberger leads Emerald’s Scientific and Clinical Affairs team and also supports strategic business development initiatives. Currently based in Madrid, he is fluent in English, Spanish, and German, and has extensive experience across all therapeutic areas Internal Medicine (CV, Metabolic, CNS & Pain, Nephrology, OTC line), Inflammation and Immunology, Vaccines, Oncology, Rare Diseases, and Hospital line.

Johannes Wolff, MD, PhD is CMO and founder of oncology consulting Wolff LLC. Trained originally as pediatric hematologist oncologist in Germany, he had a three-decade academic bedside medicine career in Germany, Canada and the USA, being faculty in 6 universities and professor in four of those, and calling MDAnderson Cancer Center his academic home. This was followed by one decade of pharmaceutical industry employment in Clinical development, Medical Affairs and Safety, calling AbbVie his pharma home. In his consulting role he now works out of Seattle and supports multiple sponsors and CROs mainly focusing on oncology early drug development and data analysis. Dr Wolff has published over 200 peer-reviewed journal articles, and more recently You-Tube teaching videos address topics such as Kaplan Meier curves, or BOIN design.

Disclosures:
Dr. Hegenberger reports no relevant disclosures. Dr. Wolff is a scientific advisor and consultant to Emerald Clinical Trials.

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