The contents of this article are informational only and are not intended to be a substitute for professional medical advice, diagnosis, or treatment recommendations. This editorial presents the views and experiences of the author and does not reflect the opinions or recommendations of the publisher of Ophthalmology 360.
By Yesha Raval, MS, and Andrew D. Pucker, OD, MS, PhD
Successful enrollment in ophthalmic clinical trials hinges on strategic planning, robust partnerships, and meticulous execution. By leveraging data-driven insights, fostering strong relationships with clinical sites, and selecting experienced investigators, sponsors can enhance recruitment and retention, ensuring efficient trial completion.
Understanding enrollment metrics
A recent technical report examined enrollment trends in ophthalmic clinical trials, analyzing data from 2,229 trials evaluating 980 drugs across 854 sponsors.1 The authors highlighted critical patterns in recruitment for common indications such as macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. This analysis provides valuable benchmarks for enrollment, site requirements, and study timelines, aiding sponsors in planning and budgeting for future trials and helping Lexitas refine its approach to modeling future studies for more accurate projections. These projections are critical given that the top reason for a trial to fail is the lack of participants.2,3
To establish realistic enrollment timelines, sponsors must carefully assess key metrics such as enrollment rate, screen failure rate, recruitment time, and retention rate. These factors directly impact the feasibility of meeting recruitment targets and study completion timelines, which, in turn, impact the budget.
For instance, a low enrollment rate may signal the need for additional sites or improved site engagement strategies,1 while a high screen failure rate could indicate overly restrictive eligibility criteria, leading to costly delays. A longer-than-expected recruitment time could result from potential challenges but may signal the need for a recruitment vendor, which specializes in patient outreach, leveraging digital campaigns, referral networks, and site engagement strategies to accelerate enrollment. Similarly, tracking site activation time helps sponsors identify bottlenecks that may slow trial initiation, while a high dropout rate can compromise study power and data integrity.
By leveraging historical trial data and proactively monitoring these enrollment indicators, sponsors can refine site selection, adjust recruitment strategies, and mitigate risks—ultimately enhancing the efficiency and success of ophthalmic clinical trials.
The role of site relationships and CRO partnerships
Contract research organizations (CROs) play a critical role in managing the scope, timeline, and budget of clinical trials while ensuring data integrity and regulatory compliance. Beyond logistical oversight, they serve as a strategic link between sponsors and sites, leveraging their industry expertise to align the right sites with the right studies. Because CROs have deep industry knowledge and established relationships, they understand the key players and unique attributes that make certain sites successful for specific trials, while recognizing that not all sites are equally suited for every study. This is especially true in ophthalmology trials, where specialized equipment, imaging protocols, and investigator expertise vary significantly across sites.
Partnering with an experienced ophthalmology-focused CRO is foundational to successful trial enrollment, as they have access to specialty sites and investigators who, in turn, have access to eligible patient populations for a given indication. CROs also bring insight into site performance capabilities, operational strengths, and potential bottlenecks, allowing them to make data-driven recommendations for site selection. By leveraging their experience, CROs help sponsors engage with high-performing investigators and seamlessly integrate trial awareness into standard clinical workflows.
Collaborations with ophthalmologists, subspecialists, optometrists, and surgery centers further enable direct engagement with eligible patients, ultimately impacting trial efficiency and success.
Projecting enrollment rates and timelines
Accurate enrollment projections are a critical component of trial planning, ensuring that recruitment goals are both achievable and aligned with study timelines and budgets. This process begins with a detailed review of protocol inclusion and exclusion criteria, study design, and potential barriers to enrollment, such as patient burden, visit frequency, and overall study length. These factors directly impact recruitment feasibility and must be carefully evaluated to prevent delays.
Realistic enrollment projections are developed by analyzing historical trial data, feasibility assessments, and input from experienced sites. Past studies with similar indications, phases, and locations provide insights into expected recruitment rates and potential challenges. Working with an experienced CRO provides access to granular historical trial data, site performance metrics, and benchmarking tools that help make more informed decisions about where and how to recruit patients. Internal feasibility tools likewise help refine these projections by incorporating insights on site interest and investigator-reported capabilities.
Utilizing data registries
Part of historical data gathering for enrollment projections involves reviewing industry trials within the same indication to understand past recruitment trends and site performance. Comprehensive data registries, such as GlobalData.com (London, United Kingdom) and ClinicalTrials.gov, provide access to historical enrollment metrics across various indications and study phases. These registries compile information from multiple sources, including clinical trial databases and published studies, allowing for a broader analysis of recruitment feasibility and refined projections of enrollment rates and timelines.
However, one drawback of these databases is that data accuracy and completeness are dependent upon the party entering the data into the systems,1 meaning that the data may be partially missing or lack site-level performance insights such as specific enrollment rates, screen failure percentages, and site-specific challenges. Without this level of detail, sponsors must supplement registry data with internal feasibility assessments, CRO databases, and investigator input to make more informed decisions on site selection and resource allocation.
Value of investigators as thought partners
Beyond data analysis, direct collaboration with experienced investigators and research centers helps ensure enrollment projections reflect real-world recruitment patterns. Investigators provide critical insights into actual patient availability, competing trials, and logistical challenges that may not be evident in historical data alone. Their firsthand experience with patients allows for early adjustments to recruitment strategies, such as expanding site networks, refining inclusion criteria, or implementing targeted patient outreach efforts—ultimately minimizing delays and optimizing resource allocation.
The size and scope of a study also influence enrollment strategies. Larger studies benefit from industry averages and broad data analyses, leveraging historical trends to predict recruitment rates. In contrast, smaller studies rely more on direct communication with investigators and selected sites, often prioritizing those with proven performance and a strong commitment to meeting enrollment targets. Because investigators are closely involved in patient care, they also serve as thought partners in study design, protocol feasibility, and retention strategies. Their input helps sponsors anticipate site-level challenges, patient burden, and realistic enrollment timelines, leading to more practical, patient-centric study designs that enhance both recruitment efficiency and data quality.
Enrollment projections and site selection
Successful enrollment in ophthalmic clinical trials is built on precise projections and strategic site selection, both of which are deeply interconnected. Accurate enrollment forecasting relies on a multifaceted approach that integrates historical trial data, feasibility assessments, investigator insights, and real-world recruitment patterns. However, even the most data-driven projections can falter without thoughtful site selection, making it a critical factor in meeting recruitment targets.
Selecting the right clinical sites goes beyond identifying locations with ophthalmology trial experience—it requires evaluating a site’s specialty expertise, access to the target patient population, regulatory environment, and facility capabilities. Sites with a proven track record in similar studies not only improve the likelihood of meeting enrollment goals but also contribute to higher-quality data and better patient retention. Because investigators play a key role in both recruitment and protocol feasibility, engaging them early ensures that studies are practical, patient-centric, and aligned with real-world clinical workflows.
Collaborative approach for successful delivery
While enrollment projections and site selection are critical, successful execution requires a strong partnership between sponsors and CRO partners. A CRO’s projections are built on historical data, feasibility assessments, and site performance insights, but these models should be viewed as a starting point for discussion rather than a fixed outcome. Sponsors should feel comfortable challenging projections, asking questions, and working collaboratively with their CRO partner to refine expectations and strategies.
By maintaining an open dialogue, sponsors and CROs can identify potential enrollment challenges early, adjust recruitment approaches proactively, and ensure alignment on study goals. This partnership approach fosters greater flexibility, transparency, and shared accountability, leading to more accurate planning and better study execution.
Ultimately, successful enrollment is not about a single entity making projections—it is about sponsors and CROs working together to make informed, data-driven decisions that lead to trial success.
Andrew D. Pucker, OD, MS, PhD, is the owner of Eminent Ophthalmic Services. He has served as a consultant for Lexitas Pharma Services, Alcon, Bausch + Lomb, and Electric Indigo. He can be reached at [email protected].
Yesha Raval, MS, is the Operational Strategy Director for Lexitas Pharma Services. She can be reached at [email protected].
References
- Pucker AD, Derthick N, Scott L. Running the enrollment numbers on ophthalmic clinical trials in the united states. Optom Vis Sci. 2024;101(8):523-529. doi:10.1097/OPX.0000000000002174
- Briel M, Olu KK, von Elm E, et al. A systematic review of discontinued trials suggested that most reasons for recruitment failure were preventable. J Clin Epidemiol. 2016;80:8-15. doi:10.1016/j.jclinepi.2016.07.016
- Kasenda B, von Elm E, You J, et al. Prevalence, characteristics, and publication of discontinued randomized trials. JAMA. 2014;311:1045-1051. doi:10.1001/jama.2014.1361
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