A recent FDA decision to reject a drug submission due to an inability to demonstrate benefit in the small fraction of U.S. patients that were enrolled has sent a clear and urgent signal to trial sponsors: Relying heavily on ex-U.S. data is a risky development strategy and may not be sufficient to support an FDA approval. Outcomes among U.S. patients can differ meaningfully from those abroad, raising concerns about the generalizability and reliability of trials accruing predominantly outside of the U.S.

The FDA’s decision reflects a regulatory reality: ex-U.S. data have to be applicable to the U.S. population and its medical practice. The FDA approves drugs for the U.S. population, and clinical trial results are therefore most persuasive when they enroll more U.S. patients who mirror the intended treatment population.

But increasing U.S. enrollment, particularly among patients who lack convenient access to an academic medical center, requires overcoming a few persistent structural barriers:

• High Site Burden: Many providers lack the time, staff, or infrastructure to take on trial participation without added support.
• Operational Misalignment: Trial protocols are rarely designed with these sites in mind, making activation and participation unnecessarily complex.
• Limited Inclusion of Community Sites: Sponsors often overlook rural or community sites when designing trial enrollment strategies, which reduces incentives for these sites to invest in the infrastructure needed for participation.

These barriers have long relegated most U.S. accrual at large academic medical centers in urban areas, leaving out patients treated in community settings, such as hospital systems, IDNs, and independent practices, in rural, exurban, and urban areas with challenges like transportation, traffic congestion, and limited clinical trial infrastructure.

To meet these challenges head-on, clinical research must evolve. Sponsors must begin to expand their site choices to make it easier for patients, like those who are seen in the community and in rural locations. To help build this capacity, the design and conduct of trials need to keep operational simplicity in mind. This can be facilitated by more pragmatic designs, but even more complicated trials can be made less burdensome by embedding software tools at sites that reduce provider and research staff workload (especially around data capture). Increasing site capacity at community and academic medical centers alike can drive the participation needed to generate larger and more representative U.S. enrollment in trials submitted for FDA review.

Building and Running Trials for Today’s Regulatory Landscape

Designing clinical trials for today's regulatory environment requires rethinking how, where, and for whom studies are conducted. With greater regulatory focus on improving the number of U.S. patients in an FDA submission, there is a clear incentive for those developing innovative cancer therapies to activate sites across urban, suburban, and rural catchment areas. Broader enrollment will not just reduce regulatory risk, but provide innovative trials as a treatment option to patients being seen in community care settings who will ultimately use the therapy if approved. Importantly, selecting sites where relevant patient populations are already receiving care removes the need for patients to choose between accessing experimental care and staying close to home. 

While there are incentives to bring more trials to a broader set of U.S. sites, unlocking that access requires work. Many community sites, including those affiliated with academic medical centers, are eager to bring trials to their patients and would benefit from technical solutions and workflow enhancements that provide the capacity needed to conduct high-quality clinical research at scale. Sponsors can help reduce the operational burden for these providers through more pragmatic trial design and by equipping sites with integrated, site-embedded tools that make participation easier, particularly when it comes to data capture and documentation.

Paradigm Health is committed to enabling this model, delivering a software platform and clinical support that streamlines end-to-end trial execution so more providers can offer research opportunities to their patients. With more diverse clinical site options, sponsors benefit from faster, more efficient recruitment, higher-quality data, and infrastructure that supports a smoother path from research to market.

The following stages and focus areas are critical to ensuring sites can deliver high-quality, efficient clinical trial access for patients and drive successful enrollment and study execution.

Strategic Protocol Design and Optimization

The protocol serves as the foundation of any clinical trial, outlining the study's objectives, eligibility criteria, and data collection methods. Regulatory agencies have increasingly encouraged sponsors to consider making protocols more pragmatic and less complicated which can generate data that applies to a broader treatment population.

Designing protocols with broader eligibility and fewer intensive assessments can better reflect routine U.S. patient care. While not all trials can be made highly pragmatic, insights from frontline providers, grounded in real clinical practice, can reduce patient and research staff burden and bring trial participation closer to everyday care.

Tip #1
Work with a partner that can incorporate clinical insights and provider feedback into protocol design. By leveraging comprehensive patient understanding and provider networks, you can ensure your protocols are reaching the broadest population and are more attractive for patients and providers, reducing recruitment challenges.

Data-Driven Feasibility

Before a trial begins, feasibility assessments are performed across potential trial sites to determine whether they have the capacity to recruit patients who meet protocol eligibility criteria. Inaccurate projections can lead to poor site selection, recruitment delays, and, in the worst case, failure to enroll any patients, wasting sponsor and research staff resources.

Feasibility improves when planning is informed by real-time clinical data and input from providers within the system being assessed. This approach not only helps ensure the protocol can be executed successfully, but also supports activation of community sites, where most patients receive care, including those affiliated with academic medical centers. Selecting and activating these sites keeps patients in their usual care setting while enabling access to trials without the need to travel to a central academic location.

Tip #2
Utilize up-to-date patient population insights, combined with provider feedback within each site’s specific healthcare system. This enables sponsors to identify and activate sites best suited to meet enrollment targets and demographic requirements, including community care locations, whether independent or affiliated with academic medical centers, where most patients already receive treatment.

Precise Patient Identification and Trial Matching

Complex inclusion and exclusion criteria make identifying eligible patients increasingly challenging once a trial begins. Reactive, referral-based screening can miss patients who might qualify but are never given the chance to consider a clinical trial as a treatment option. Proactive screening can address this gap, but manually reviewing records for all potentially eligible patients is impractical and can overwhelm research staff. AI-enabled clinical trial matching, guided by clinical documentation and provider oversight, can surface a manageable list of likely eligible patients for research teams to review earlier in the process.

Tip #3
Use AI-driven patient identification to make proactive screening more precise and less burdensome. Tech-enabled clinical trial matching surfaces a broader pool of well-matched patients, giving more people the opportunity to consider clinical trials as a treatment option and helping sites accelerate recruitment.

Optimized Research Workflow and Timing

Many trials require patients to progress on initial therapy. Even with accurate early identification, patients may remain on their initial treatment for months before becoming eligible for a trial.

Providing a workflow that enables research staff to track patients and equips providers with clinical trial options increases the chances that patients can consider trials as part of their treatment decisions. Importantly, being well-prepared can reduce the time patients wait for full screening upon disease progression, a challenging phase in their treatment journey. Bridging the gap between treating providers and principal investigators within a health system ensures that patients under the care of non-PIs can still be referred to and enrolled in available trials.

Tip #4
Provide clinical and research teams with integrated tools that surface trial options at the right moment in a patient’s care journey. This not only reduces wait times for patients and providers reactively searching for suitable trials, but also strengthens the connection between treating providers and principal investigators, ensuring that eligible patients remain within their healthcare system for trial participation.

Integrated Data Capture and eSource Enablement

Accurate, high-quality data is essential for regulatory review. Manual data entry using disconnected systems creates significant burdens on research and clinical staff. Manual entry also can lead to transcription errors, data queries, and protocol deviations or other data quality concerns.

Automating data capture directly from electronic health records (eSource) can populate case report forms and reduce data entry burden for sites while improving data completeness, accuracy and traceability. This approach strengthens protocol compliance and can support faster database lock, which is increasingly important for timely submissions.

Tip #5
Use an eSource solution that captures data directly from clinical systems to reduce manual errors and streamline data collection. This improves data quality and compliance, eases burden on research sites, and helps sponsors meet stringent regulatory data quality expectations.

Leveraging Technology, Clinical Workflow and More Pragmatic Trial Design to Achieve Accrual of a Representative U.S. Population

Recent regulatory decisions underscore the importance of enrolling a representative U.S. population, with incentives now aligning across the drug development and clinical care landscape to support this goal. Ensuring all U.S. cancer patients, regardless of location, have access to innovative treatments through clinical trials is critical. Bringing trials back to the U.S., spanning urban and rural healthcare systems, demands a proactive and comprehensive approach to strengthening our research infrastructure. 

Technology and clinical systems can reduce burdens on patients, healthcare providers, and research staff. From pragmatic protocol design and optimal site selection to proactive screening, timely trial presentation, and eSource data capture, every aspect of the research paradigm must be optimized. While various vendors may address individual challenges, a seamless end-to-end platform offers the best path to meaningful improvements for patients, healthcare systems, and sponsors alike.

Paradigm Health delivers an AI-powered, end-to-end platform deployed across a nationwide network of healthcare providers covering both urban and rural areas. We partner with clinical sites to optimize their trial portfolios for their patient populations, accelerate recruitment through AI-enhanced clinical trial matching, and reduce data entry burden with eSource capabilities that ensure high-quality data.

Commercial sponsors collaborate with Paradigm Health in several ways. Paradigm Health supports expanding access to high-quality clinical trial sites across the U.S. Its data-driven site selection, AI-enhanced proactive screening, and eSource capabilities have been utilized by pharmaceutical and biotech companies in both early and late-phase programs. Additionally, Paradigm Health has partnered with sponsors to optimize clinical trial designs, making them more reflective of routine clinical care, reducing patient burden, and enhancing the generalizability of study results.

Paradigm Health is committed to expanding trial access to every patient, everywhere. Whether by increasing efficiency at existing academic sites or expanding research in community and rural settings, Paradigm Health enables a technology-supported network of research-ready U.S. sites to reach a broad, representative patient population.

To learn more about our approach to making trials more efficient and accessible, contact Paradigm Health today.