In the early 1900s, Ford Motor Company pursued an ambitious experiment. Having reached a historic level of vertical integration at its River Rouge Plant in Michigan, the company began producing its own steel, glass, rubber and power, built transmissions in-house, and even ran its own railroad to move its freight (1).

The result? Without any outside help, the plant was able to take in raw materials and pump out cars at a volume never seen before.

While it might seem that the automobile manufacturing and retinal drug-development industries have little in common, they do share some guiding principles – particularly the need for speed when it comes to achieving their goals. As a result, we can learn a lot from Ford’s pioneering example about how to move past the fragmented systems that often delay retinal clinical trials, sometimes even preventing them from meeting their endpoints (2).

That wisdom will be increasingly important as our field explores a growing number of gene and cell therapies, biologics and novel delivery systems. Often large and prolonged, these trials can incorporate novel protocols and endpoints, specialized drug handling, complicated surgical procedures, and a wide geographic dispersion of sites – coupled with the imaging-heavy outcomes assessments that have long been a hallmark of retina studies (2). To meet these challenges, sponsors often must scramble to assemble patchworks of vendors, subject matter experts, communication models, contracts, documents, and standard operating protocols – while still striving to maintain enough separation between functions to prevent conflicts of interest.

Consolidating operations can make the process more manageable by removing barriers between partners, particularly the complex and lengthy contract negotiations that often slow trials or exclude qualified vendors (3). This integration also promises to benefit patients by creating a smoother, more cohesive trial experience for those involved.

Vertical integration isn’t new in the healthcare arena; in fact, some highly visible examples have captured our attention over the past decade and a half. When McKesson acquired US Oncology and Cencora bought Retina Consultants of America (4, 5), it was intriguing to envision the efficiencies that could be forged through closer working relationships between clinical research, care-delivery networks, and operational infrastructures.

To realize similar benefits, the leaders of today’s retinal trials must be able to identify the most accessible and promising approaches and understand how best to implement them at speed. Clinical ophthalmologists can contribute, too, by supporting integrated networks as principal investigators, as well as keeping tabs on what the pipeline has in store for their patients with retinal diseases.

Overcoming misconceptions

Having participated in the design and operation of myriad retinal trials, we’ve developed half a dozen best practices intended to help sponsors make the most of vertical integration. While we realize these principles may challenge conventional thinking, we’re confident they can improve efficiency, primarily by dispelling the misconceptions that so often slow down retinal research.

Across retinal trials, we want stakeholders to recognize that:

Good sites, not more sites, speed enrollment. In retina trials, the real rate-limiter is not the number of sites, but a good process for securing qualified principal investigators, certified imaging services, and an efficient patient flow. Those factors can all be streamlined through vertical integration.

Recruitment is not the main cause of bottlenecks. While the recruitment process often gets the blame for delays, a more frequent culprit is the failure to integrate a trial’s reading center into the workflow, which can lead to problems with data fidelity, image gradability, and query resolution, as well as the need for re-reads and re-screens.

Quality and speed are not a trade-off. Poor research quality is what counteracts speed in retina trials. The fastest studies are the cleanest ones, which is why a streamlined approach is needed.

Integration doesn’t cause conflicts of interest. Concerns about conflict of interest must be managed by establishing governance and boundaries between partners where needed, but the larger and more unexamined risk is the stitching together of misaligned vendors with no shared accountability.

Technology is not the solution. Unified stacks and artificial intelligence may amplify expertise, but they cannot replace retina specialists with the skills to expertly interpret optical coherence tomography images. Through vertical integration, these experts can be more easily embedded into a trial’s workflow.

Protocols should not be fixed. As retina trials move toward biomarker-informed, adaptive designs, with proteomics and clinomics shaping eligibility and endpoints, infrastructure will need to be built with that in mind. Integrated frameworks will be nimble enough to respond.

Incorporating vertical integration

But what specific strategies should be used to integrate retinal trials?

To get started, we encourage sponsors to look at the Ford model as an à la carte menu rather than a prix fixe experience, with the goal of baking just a few transformative concepts into their clinical trials.

That could mean assigning a single site management organization to support multiple trial locations; using a unified technology platform to complete everything from patient recruitment to the capture and assessment of electronic data; or asking a contract research organization (CRO) to oversee a study’s planning and execution, often working alongside independent or integrated reading centers to support interpretation of outcome measures.

Sponsors can also partner with retina-experienced training academies to ensure that their principal investigators and other site leaders are uniformly prepared.

Empowering some partners to make decisions independently can further reduce vendor handoffs, as can aligning incentives and creating seamless pathways for data flow. Of course, clear, cross-network communication should always guide these processes.

To learn more about the fundamentals of good clinical research and how they can dovetail with the principles of vertical integration in retinal trials, sponsors can check in with professional and academic organizations, including the American Society of Retina Specialists, the Pharmaceutical Business Conference Group and its annual Clinical Outsourcing Group event series, the Tufts Center for the Study of Drug Development and the Society for Clinical Research Sites.

Involving clinicians

Integration can open the door to clinician involvement in retinal research, as well.

Although some ophthalmic practices are specifically dedicated to research, others focused on clinical care can serve as trial sites through organizations such as the DRCR Retinal Network or NVision Clinical Research.

Smaller practices can participate by partnering with CROs, site management companies, or academic institutions. By tapping into integrated mentorship pathways, these practices can cultivate their own principal investigators.

Ophthalmologists who don’t want to become principal investigators can serve as sub-investigators or refer patients for trial enrollment. In addition, all clinicians can now be considered data stewards, as their routine imaging and documentation fuels trial recruitment and real-world evidence.

The integration of clinicians into retinal research can certainly make a big difference – not only by helping to advance novel treatments, but by introducing them to a broader population of patients sooner.

Looking ahead

In the decade ahead, we can expect changing regulatory benchmarks to realign the way we approach retinal research. While investigators have typically needed to conduct two pivotal trials to support the approval of any retinal treatment, the U.S. Food & Drug Administration will now require just one as its default standard (6).

That shift has the potential to save time and money for our field, but it will also mean that sponsors must run smarter, more sustainable late-stage retina studies that have the greatest possible chances of achieving regulatory success – a goal we believe can be best accomplished through integration.

In an era that has brought us landmark therapies such as Luxturna (7) and Eylea (8), vertical integration offers a unique opportunity to streamline and optimize the complex clinical trials that will usher in the next wave of advanced retinal treatments. By taking even small steps toward integration, trial sponsors can significantly speed innovation, and that will go a long way toward improving quality of life for the patients at the center of this challenging but deeply meaningful process.