Despite the introduction of many novel ophthalmology treatments in recent years, there is still need for more cost-effective and patient-friendly treatments that reduce patient burden and provide improved outcomes. With an aging population and increasing incidence of chronic diseases, the number of patients suffering from eye disorders continues to rise. Drug developers have responded, leading to a full pipeline with many early-phase candidates advancing to later-stage clinical trials. Upscaling to a global landscape is critical to the success of a program. Selection of an ophthalmology-experienced provider of clinical research solutions and vendors with a vast global regulatory reach that implements key clinical, scientific, and regulatory strategies early on is crucial to ensure on-time trial delivery and the highest-quality data.
Drivers for Expansion of Late-Stage Ophthalmic Clinical Trials
Over the past decade, the field of ophthalmology has seen remarkable progress, introducing new treatments for a broad spectrum of conditions, including age-related macular degeneration (AMD), geographic atrophy (GA), diabetic macular edema (DME), and inherited retinal diseases. Notable examples are Syfovre (pegcetacoplan), Izervay (avacincaptad pegol), Vabysmo (faricimab), and Eylea HD (aflibercept), enhanced by the approval of several biosimilars, primarily for treatments based on blockade of vascular endothelial growth factor (VEGF).
This surge in interest can be attributed to a deeper understanding of disease pathogenesis, advances in novel and more targeted therapy modalities, and increasing prevalence of age-related eye diseases, such as macular degeneration, as well as chronic diseases, such as diabetes, obesity, hypertension, thyroid disorders, and a variety of autoimmune diseases, which are linked to a rise in eye disorders. Despite recent advancements, there remains a significant need for treatments that are more cost-effective, patient-friendly, and longer-lasting and require less frequent administration, thereby reducing patient burden and improving their outcomes. Reflecting these needs, the ophthalmology drug development pipeline is robust. As of early 2024, the ophthalmic late-stage pipeline includes 14 compounds targeting AMD that had reached phase II/III development stages. Additionally, there is considerable focus on the development of gene therapies for inherited retinal diseases. The landscape of late-stage clinical trials for treating eye disorders is expected to grow further, necessitating an expansion in the size and scope of these trials.
The Importance of a Strong Global Network in Ophthalmology Clinical Trials
The competitive landscape and larger sample sizes required for success necessitates a broad, global infrastructure for late-stage clinical trials to test the efficacy and safety of ophthalmology drug candidates. These drugs, once approved, are often intended for global markets. Selecting a provider of clinical research solutions with deep therapeutic expertise, global regulatory knowledge, and strong consulting capabilities to support protocol optimization will greatly enhance the efficiency of study initiations and improve the quality of data.
In addition to a global network of investigator sites, it is essential to have well-trained and experienced staff on the ground at those sites. Due to the sensitivity of the endpoints for many ophthalmic trials (e.g., potential for bias, operational variability in collection), partnership with technology vendors that have validated solutions and global reach, along with a strong monitoring team to ensure quality data, is important.
Choosing a partner that will leverage its internal resources, without the need for contracted staff, to scale operations effectively while harnessing indication-specific expertise, country-specific insights, and strong vendor partnerships, is vital for mitigating risks associated with these trials.
Strategic Site Selection
In global late-stage clinical trials, it is impractical to include sites in every country where a drug might ultimately be marketed. Therefore, selecting an effective mix of sites is crucial to ensure high-quality outcomes and appropriate patient diversity and to circumvent potential regulatory or enrollment delays. This mix also supports post-study access and the capacity for additional data collection essential for advancing product commercialization.
A robust, data-driven strategy is necessary, including a thorough analysis of past enrollment rates by country, ongoing competing studies, and the availability of qualified sites with suitable patient populations and regulatory expertise. Other factors to consider include the standard of care, the availability of insurance reimbursements, and the potential for optimizing enrollment across countries with disparate approval timelines.
Assessing competing studies aids in determining if a country’s clinical landscape within that indication is oversaturated, which may impede patient availability and subsequent enrollment. Additionally, sites engaged in multiple trials may experience operational strain, affecting their performance across trials.
The qualifications of sites go beyond capability; they must also have the right equipment, access to the appropriate patient population, and a genuine motivation to participate in a specific trial. The care standard at each site should align with the trial protocol to prevent any adverse effects on the study’s validity.
Furthermore, for many ophthalmic indications, variations in the standard of care are expected, particularly in global trials, as treatment preferences and available therapies may differ significantly among countries. Such differences influence the choice of comparator drugs, supply logistics, and insurance reimbursement strategies. Additionally, recently launched treatments, like those for GA, may not be available in all countries, introducing further variability in care standards.
Regulatory demands also differ across countries, affecting what is deemed acceptable among procedures and comparators in trial protocols, as well as what is most clinically relevant to measure to evaluate the benefit versus risk of the therapy. Adjustments may be necessary to gain study approval and, to achieve marketing approval, trials might need to include a specific percentage of participants from the host country. The need to meet such requirements can have a significant impact on the country site mix.
Ultimately, the number of sites and their geographic distribution must be carefully planned to balance the timely completion of the trial with the need for a diverse patient base. This is critical to ensure that the drug reaches the market efficiently and the sponsor gathers adequate data to secure its approval. Trials in certain regions may face time constraints, which may limit site selection in those areas.
Essential Patient-Centric Approach
As study competition intensifies and the footprints of global clinical trials expand, prioritizing site and patient support is crucial to prevent delays in study initiation and to ensure that project timelines are met. Patient-relevant trial designs are used to drive quality data for all downstream stakeholders (patients, providers, regulators, and payers). Successful trial implementation necessitates a proactive strategy that incorporates advanced technology solutions to address the needs of sites and patients. These should include options for electronic consent (eConsent), electronic clinical outcome assessments (eCOA), home-health nursing services, mobile eye care solutions, collaboration with patient advocacy groups, and comprehensive patient concierge services.
A deep understanding of the patient journey is vital to designing the best trial and selecting the most effective solutions to foster successful recruitment strategies. This might involve utilizing electronic medical records; conducting supportive onsite chart reviews; providing dedicated in-house study coordinator support; engaging with advocacy groups; and employing technologies that facilitate the identification of potential participants via ophthalmic imaging data. Social media outreach, educational tools, site-specific recruitment plans, and initiatives to support sites in following up on patient referrals have a significant impact on effective engagement.
Ensuring diversity within clinical trials also demands a patient-centered approach. This involves establishing a broad and inclusive global network of ophthalmology sites and crafting a robust strategy that addresses diversity across geographic, cultural, and social backgrounds and ensures representation across different races, ethnicities, socioeconomic statuses, and genders.
Increasing diversity leads to a more heterogeneous patient population, which necessitates larger participant numbers to allow for confident measurement of clinically relevant effect sizes and for informative subgroup analyses. Maintaining a comprehensive global network that provides access to a diverse patient pool is critical for the successful implementation of late-stage ophthalmic clinical trials.
Optimizing Late-Stage Retinal Clinical Trials
Operationalizing ophthalmic clinical trials requires an alignment across clinical development, scientific research, and regulatory compliance. A thorough understanding of the disease pathology of the specific eye disorder under study, the drug’s mechanism of action (MoA), and the demographics of the patient population — including its subgroups — is crucial. The implementation speed of trials is also influenced by accelerated development designations, which are often critical elements in shaping the clinical development strategy.
The pathology of the disorder and the specific molecular targets underpin the design and MoA of the drug candidate. Recognizing the affected signaling pathways and cellular processes enables researchers to predict the drug’s efficacy and potential off-target effects. Additionally, the use of diagnostic, predictive, pharmacodynamic, and imaging biomarkers enables identification of patient subgroups most likely to benefit from the therapy and facilitates monitoring their responses. Delivery methods also play a role. For example, sustained- or controlled-release systems, including implants, decrease the frequency of treatment, while intravitreal injections provide targeted delivery but require training and oversight to ensure patient safety. The same is true for newer technologies, such as delivery of gene therapies using viral vectors and nanoparticle carriers.
Accelerated development designations like the FDA’s Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval are designed to expedite the development and review of drugs that address unmet medical needs, potentially speeding up the availability of treatments for patients. These programs allow for more frequent interactions with the FDA throughout development, which can have a significant impact on shortening development timelines. Drugs targeting rare diseases may also qualify for Orphan Drug Designation, which offers tax advantages, market exclusivity, and accelerated timelines. For many candidates with these designations, post-marketing studies (phase IV trials) are required to gather additional information about safety and efficacy in broader populations.
When formulating the clinical development strategy, it is essential to consider that most late-stage (phase II/III) trials are randomized controlled trials, providing the highest level of evidence for assessing safety and efficacy. Such trials require large sample sizes to statistically estimate treatment effects and evaluate safety across diverse patient populations. Double-masked studies, where neither patients nor investigators know the treatment assignments, are recommended in order to minimize bias in reporting of safety or efficacy parameters. These can be complex to implement in ophthalmology, where multiple investigators are often required per site when surgical or injectable delivery mechanisms are commonplace. Where possible, trials should have extended durations and follow-up periods to capture both immediate and prolonged treatment impacts, which is particularly vital for chronic eye conditions.
Primary and secondary endpoints must reflect the treatment’s impact across dimensions important to patients, providers, regulators, and payers. Common primary endpoints include best corrected visual acuity, measured via ETDRS eye charts and functional vision, which assesses the impact on daily activities. Secondary endpoints might encompass structural changes observable through imaging techniques, quality of life metrics, and overall safety.
The target patient population should include individuals most likely to benefit from the treatment, spanning various demographic categories, and exclude those with conditions that might confound the results. The active comparator should generally be the current standard of care, allowing direct efficacy comparisons with the new treatment. In some scenarios, a placebo arm is unavoidable, especially when no standard treatment exists; occasionally, historical controls are utilized if past trials provide robust data.
With respect to trial design, it is challenging to conduct fully decentralized trials for ophthalmology indications, owing to the requirements for imaging and visual acuity assessments, which must be performed at clinical sites. In the United States, mobile eye buses equipped with validated tools can be used to facilitate assessments at patients’ homes for long-term studies, particularly for inherited retinal diseases, though this approach is not approved in other regions.
Successfully Executing Ophthalmology Clinical Trials with an Experienced Provider of Clinical Research Solutions
At the PPD™ clinical research business of Thermo Fisher Scientific, we excel in managing ophthalmology clinical trials, focusing on the substantial benefits we can deliver to our clients. Our deep experience, exemplified by successfully conducting 62 studies with nearly 10,000 patients across 2,300 sites worldwide, ensures that our clients receive not only expertise but also customized solutions that cater specifically to the unique needs of ophthalmology drug development. Through our global network of more than 600 retinal specialists and a robust internal team, we streamline the study startup and approval process, enabling faster market entry and quicker patient access to new therapies.
Our commitment extends beyond standard trial execution; we emphasize creating real-world solutions that enhance trial efficiency and outcomes. This includes rigorous training for clinical research associates (CRAs) and clinical science liaisons (CSLs), ensuring top-tier data integrity and regulatory compliance. Furthermore, our collaborations with leading ophthalmic imaging and visual acuity vendors enable us to support our clients in maintaining high standards throughout the trial process.
By integrating advanced technologies, expanding access to patient registries, and employing electronic medical records, we help reduce operational burdens, maximize patient engagement, and streamline the pathway to innovative treatments. Our approach is not just about conducting trials but about fostering sustainable partnerships that support the continuous advancement of ophthalmology therapies, ensuring that each phase of the clinical trial process not only meets but exceeds the expectations of our clients. This client-centric focus is pivotal as we work together to turn promising scientific insights into accessible, life-changing therapies.
Harnessing Innovations for Future Success in Ophthalmology
The evolving landscape of ophthalmology clinical trials, driven by scientific advancements to address an increasing disease burden from an aging population and rising chronic conditions, demands groundbreaking yet cost-effective treatments for a diverse array of ophthalmic diseases from anterior to posterior indications. Successful outcomes hinge on a deep understanding of disease pathology, strategic site selection, the integration of advanced technologies, and diverse patient strategies to enhance site and patient engagement.
As a leader in driving ophthalmology clinical trials forward, combined with access to the broader Thermo Fisher Scientific resources and our extensive global reach and deep expertise, we are the ideal partner for therapy developers seeking to navigate the complexities of modern clinical studies. We enable you to implement solutions that de-risk drug development by ensuring communication and continuity across drug manufacturing and clinical research. By continuously advancing our partnerships and expanding our technological capabilities, we are committed to reducing operational burdens and enhancing the efficiency of your clinical trial.
Partner with us to advance innovative solutions and exceed patient needs. Let’s turn your promising scientific insights into accessible, life-changing therapies.