Expanding access, enhancing research: The evolving landscape of ophthalmic clinical trials

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The ophthalmic drug development industry is undergoing significant transformation, marked by unprecedented advancements in therapies and expanding indications for treatment. Gene therapy, next-generation biologics, novel mechanisms of action, and cutting-edge drug-delivery systems hold immense potential to revolutionize care for millions of patients. However, these breakthroughs come with increased trial complexity and regulatory scrutiny, placing greater demands on investigators and clinical sites.

This evolving ecosystem is also shaped by demographic trends. An increasing aging population is driving a surge in age-related ocular diseases such as macular degeneration, cataracts, and diabetic retinopathy, further increasing the demand for specialized care. Unfortunately, at the same time, the ophthalmology workforce is shrinking, exacerbating existing challenges in meeting patient demand and research participation. The resulting workforce shortage has profound implications for both patient care and clinical research, highlighting the need for innovative solutions to address these challenges.

Growing complexity demands expertise

As trials grow more intricate, success hinges on the ability to navigate scientific, regulatory, and logistical hurdles. Clinical trial success requires meticulous planning, robust site management, and strategies to maintain an uncompromised level of data integrity, patient safety, and regulatory compliance. This is where experienced partners, including contract research organizations (CROs), play a pivotal role.

CROs can provide end-to-end trial management services, serving as a vital link among sponsors, sites, and patients. By streamlining processes, monitoring compliance, and optimizing recruitment strategies, CROs help accelerate timelines and maintain the integrity of trial outcomes. Well-equipped CROs can develop a tailored site list best suited to the needs of a clinical program, significantly contributing to its success.

Investigational sites

Types of sites can include institutional centers, those that are part of a site management organization (SMO), non-SMO sites, and others. Institutional sites often provide robust infrastructure and access to specialized resources, whereas independent clinics bring localized expertise and strong community ties. SMOs are a distinct category that either own or manage investigational sites, providing centralized services to improve efficiency and regulatory compliance.

SMOs provide services that have the potential to shorten recruitment periods, offsetting their added site costs. They can contribute to the success of a program, but their rise has led to a shift away from independently operated research sites. These independent clinical sites are crucial for maintaining diversity and innovation, providing localized expertise, and ensuring strong community ties in the clinical research ecosystem.

Addressing specialist shortages

The number of ophthalmologists in the US is projected to decline by 12% by 2035, while the demand for eye care services is expected to increase by 24%, leading to a significant supply-demand mismatch.¹ With fewer ophthalmologists available to meet growing patient demands, more clinical sites must participate in trials to ensure that research progresses efficiently and that new treatments reach patients in a timely manner.

Expanding site participation can help alleviate bottlenecks in recruitment, diversify trial populations, and improve access to innovative therapies, ultimately strengthening the research infrastructure needed to support the future of ophthalmic care. Investigator shortages are particularly acute in rural areas, where only 4% to 8% of ophthalmic subspecialists practice, despite 13% to 18% of patients residing in these regions.² This geographic disparity undermines efforts to ensure diverse and representative clinical trial populations—a priority emphasized by the FDA to improve health equity and ensure that new treatments are effective across all demographics.

The consolidation of sites into SMOs, while addressing some recruitment and efficiency challenges, may exacerbate this issue by concentrating trials at fewer locations and creating competition among studies for the same pool of participants.³ To mitigate these challenges, the industry must strike a careful balance between leveraging SMO efficiencies and fostering non-SMO site participation.

There are also significant resource constraints putting pressure on the clinical trial ecosystem. Research centers are experiencing shortages of skilled technicians, clinical research coordinators, and physician researchers, all of whom are crucial for trial success. While SMOs can alleviate some of these challenges by helping share resources, specialization is often lost when centers contract and consolidate.

Implications of low participation

Fewer non-SMO sites participating in research could lead to competition for sites and patients, resulting in increased costs and timeline delays. These delays can hinder the development of innovative treatments, slowing patient access to potentially life-changing therapies, and result in increased treatment cost for consumers and society at large. The lack of investigator diversity may also limit the generalizability of trial results, posing risks to broader patient populations.

The consolidation of research efforts under SMOs must be complemented by initiatives to support and expand the pool of non-SMO investigators. This includes providing resources, training, and incentives to encourage clinicians to engage in research.

Strategies to engage clinicians in research

Adapting to the changing clinical trial ecosystem and addressing these challenges requires a multifaceted approach. Sponsors and CROs can leverage specialized SMOs to help mitigate investigator shortages and site limitations, as SMOs may encourage more sites to participate.

Despite the benefits of participating in research, many clinicians face barriers such as time constraints, administrative burdens, and financial disincentives. Addressing these challenges can encourage greater engagement in research. Clinicians and sites can actively engage in research beyond the SMO model through the following strategies:

Building capabilities by teaming with experienced investigators, hiring research-trained clinicians or clinical coordinators, and completing necessary certifications and training

Integrating digital tools with artificial intelligence into ecosystems to help manage trial operations and balance practice workload with clinical research

Serving as a referral site for another clinician engaging in research

Collaborating with CROs and drug/device development companies as a researcher, adviser, or consultant

Publishing data and articles that will both build credibility and engage with the research community at large

Ophthalmic clinicians have a unique opportunity to contribute to this effort. Participation in research not only advances the field but also strengthens professional development, enhances patient trust, deepens community ties, and provides access to cutting-edge treatments. Supporting non-SMO investigators and fostering collaboration across the clinical trial ecosystem will ensure that ophthalmology continues to thrive in the face of growing demands and challenges.

Conclusion

Clinical trials are essential to driving innovation and improving patient outcomes in ophthalmology. As the research ecosystem evolves, maintaining a diverse and well-supported pool of investigators is vital. By addressing the challenges posed by trial complexity, workforce shortages, and site consolidation, we can create a research environment that is both efficient and inclusive.

By fostering collaboration among sponsors, CROs, SMOs, and non-SMO investigators, the industry can overcome current challenges and ensure the continued advancement of ophthalmic care. A diverse mix of SMO and non-SMO sites is necessary to ensure clinical research remains innovative, efficient, and widely accessible with unique perspectives and expertise.

Lejla Vajzovic, MD, FASRS

E: lejla.vajzovic@gmail.com

Vajzovic is director of the Duke Vitreoretinal Surgery Fellowship Program and a tenured professor of ophthalmology with expertise in adult and pediatric vitreoretinal surgery and disease, Duke University School of Medicine in Durham, North Carolina.

Yesha Raval

E: yesha.raval@lexitas.com

Raval is the operational strategy director at Lexitas.

References

1. Berkowitz ST, Finn AP, Parikh R, Kuriyan AE, Patel S. Ophthalmology workforce projections in the United States, 2020 to 2035. Ophthalmology. 2024;131(2):133-139. doi:10.1016/j.ophtha.2023.09.018

2. Wang SY. The rural shortage of ophthalmic subspecialists. JAMA Ophthalmol. 2025;143(2):125. doi:10.1001/jamaophthalmol.2024.5704

3. Pareek R. Site management organization: a trend in the clinical trial domain. Roots Analysis. December 15, 2021. Accessed January 30, 2025. https://www.rootsanalysis.com/blog/site-management-organizations-smos-a-trending-term-in-the-clinical-trial-domain/