Over 50%. That’s the current screen failure rate across more than 350 active clinical trials in the retina space. Half of all potential participants never move past the initial screening phase. This wasn’t always the case, but it has become the new reality and a stark indicator that something in the clinical trial ecosystem is misaligned.
The question isn’t merely why patients are being screened out. It’s whether the increase in screen failures is a sign of shifting study designs, changing site performance, or perhaps something deeper: a consequence of the industry’s own successes.
The Rise of Precision and Complexity
Over the past decade, clinical research across all therapeutic areas has benefited enormously from advances in technology and methodology. In retina trials specifically, innovations in imaging modalities, computer-aided modeling, and artificial intelligence-based software have revolutionized patient assessment and trial design. These tools have made it possible to measure disease with unprecedented precision, predict outcomes more accurately, and identify potential responders earlier in the disease course.
Yet while the tools and techniques have advanced, the fundamental goal of clinical trials remains the same: sponsors, sites, and CROs strive to run each study as efficiently as possible, generate the highest-quality data, and shorten timelines to bring life-changing treatments to patients faster. This tension, between technological advancement and operational efficiency, lies at the heart of the current challenge.
A Success That Breeds Complexity
In many ways, today’s challenges are the direct byproduct of prior successes. The very advances that enable earlier detection and better-targeted interventions have also narrowed the pool of eligible patients. Inclusion and exclusion criteria have become increasingly stringent, driven by the need for precision and regulatory rigor. Whereas previous trials might have enrolled broadly, contemporary studies demand patients meet a combination of imaging, biomarkers, disease stage specifications, and sometimes even genetic or systemic criteria.
This narrowing of eligibility is only part of the story. Simultaneously, the number of retina trials recruiting at any given time has grown dramatically. Multiple studies compete for the same small populations of qualified patients, creating bottlenecks that inevitably increase screen failures. Sites are asked to juggle competing priorities, often without additional resources to manage the demand, while sponsors expect enrollment targets to be met on time. The result is a system that is, by design, strained.
The Cost of Screen Failures
Screen failures have always been recognized as an operational cost, but the scale of the problem today carries both immediate and long-term consequences. Consider the following impacts:
- Financial Waste: Each screen failure represents resources spent on recruitment, imaging, labs, and staff time, often amounting to millions of dollars per trial. These expenditures, while necessary for maintaining rigorous study standards, generate no useful data.
- Operational Strain: Sites tasked with high-volume screening face mounting pressure to deliver enrollment targets. When screen failures are frequent, staff morale suffers. Burnout and disengagement are real risks, leading to turnover, retraining costs, and operational inefficiencies.
- Sponsor Confidence: Consistently high screen failure rates can erode trust between sponsors, CROs, and sites. Delayed enrollment may extend trial timelines, increase costs, and limit the sponsor’s ability to initiate future studies at the same sites.
- Patient Access: Perhaps most importantly, delays in enrollment slow the availability of potential life-saving treatments to the patients who need them. The very individuals these trials are designed to help are affected, creating a tangible human cost that extends beyond spreadsheets and operational metrics.
Root Causes: More Than Meets the Eye
While the immediate drivers of high screen failure rates may appear straightforward, stringent inclusion criteria and multiple competing trials, the underlying causes are more systemic. Several factors converge:
- Technological and Methodological Advances: AI, advanced imaging, and predictive modeling have enabled more precise patient selection. However, greater precision often comes at the expense of quantity, shrinking the pool of eligible participants.
- Competitive Trial Landscape: With numerous studies recruiting simultaneously, sites are forced to prioritize certain trials, sometimes at the cost of slower enrollment or higher failure rates in others.
- Operational Misalignment: The demands of trial sponsors and CROs may not always match site capacity or patient availability. This misalignment creates bottlenecks that increase screen failures and operational stress.
- Incentive Structures: Current compensation models often emphasize completed enrollments rather than the quality of screening processes. This can lead to overburdened site staff and a focus on quantity over efficiency, inadvertently exacerbating screen failure rates.
Why This Matters Now
High screen failure rates are not a minor inconvenience, they are a signal that the current clinical trial model is under pressure. The implications extend beyond operational inefficiencies:
- Economic Consequences: Delays in trial completion inflate costs and reduce return on investment for sponsors, potentially limiting the funding available for future studies.
- Reputational Impact: Repeatedly missing enrollment targets can damage the credibility of sites and CROs, affecting their ability to participate in subsequent trials.
- Patient-Centric Considerations: The ultimate goal of clinical research is patient benefit. Every delay or failure represents not just financial or operational loss but a delay in bringing potentially life-saving therapies to those who need them.
A Multifaceted Challenge Requires a Multifaceted Approach
The high screen failure rates seen in retina trials are a symptom of an ecosystem under strain, not merely a problem of recruitment. Addressing it will require a comprehensive strategy that accounts for technological, operational, and human factors.
Single-solution approaches, whether loosening criteria, increasing recruitment outreach, or adopting new software platforms are unlikely to suffice. The challenge is inherently multifactorial:
- Technology must support efficiency without excluding qualified patients unnecessarily.
- Operational practices must align sponsors, CROs, and sites around realistic expectations and resources.
- Incentive structures must encourage sustainable processes, reducing burnout while improving patient engagement.
Recognizing that screen failures are a systemic issue, rather than a site-level or sponsor-level failing, is the first step toward meaningful improvement.
Looking Ahead
The retina clinical trial ecosystem faces a choice: continue accepting high screen failure rates as an inevitable cost of doing business, or acknowledge the systemic misalignments and work toward integrated solutions. The path forward will require collaboration, innovation, and a willingness to rethink entrenched practices.
While the solutions are complex, the stakes are clear: improved screening efficiency has the potential to save not only millions in operational costs but also, more importantly, to accelerate the delivery of treatments that preserve and restore vision for patients around the world.
The challenge is real, the implications are significant, and the opportunity for meaningful change is within reach. By identifying the systemic causes of high screen failures, the industry can move from reactionary troubleshooting to proactive transformation — ensuring that clinical trials fulfill their ultimate purpose: delivering life-changing therapies to those who need them most.