Designing Clinical Trials For Hard-To-Access Patients

By Jonathan Naab, clinical supply chain professional

Clinical trials are increasingly seeking to include diverse populations across geographic and socioeconomic boundaries. This is not just for ethical reasons but also for scientific reasons, especially in these days of equity and personalized medicines. However, traditional clinical supply chain models were designed for large academic medical centers and well-established trial sites. As research expands to remote or underserved communities, supply chain design becomes a critical determinant of whether patients can participate in trials.

The Challenge Of Reaching Hard-To-Access Patients

It is important to reach patients who are deemed hard to reach due to their geographic location or socioeconomic status, as data from these patients adds validity and robustness to the trials they participate in. Responses to drugs can vary across different demographic and biological groups. This variation can stem from factors such as environmental exposure, genetics, lifestyle, and underlying health conditions. When clinical trials consistently recruit patients from a narrow pool of participants, the data may not be representative of how the therapies under consideration perform in broader patient populations. For example, some diseases disproportionately affect populations that have been traditionally underrepresented in clinical trials. Rare diseases, for instance, often require researchers to identify small numbers of patients dispersed across wide geographic regions. In such cases, the ability to reach remote patients is not merely desirable but necessary for generating meaningful clinical evidence. Designing supply chains capable of supporting these patients becomes a critical enabler of scientifically robust trials.

Regulatory authorities have increasingly emphasized the need to make clinical trial enrollment more diverse and representative. Bodies such as the FDA and the European Medicines Agency (EMA) have issued guidance encouraging sponsors to broaden the demographics of their participants and ensure that the populations under examination reflect the patients who will eventually use the therapy under investigation.

These initiatives aim to address safety and efficacy concerns when trial participants are limited to a specific group. Information on differences in responses to treatment or adverse events may only become available after market approval, when the drug is used in a broader patient population, and when trial participants are not diverse. As a result, regulators now encourage sponsors to develop strategies to expand access to clinical trials across geographic, socioeconomic, and demographic boundaries.

Regulatory And Ethical Imperatives

Reaching hard-to-access patients is therefore increasingly aligned with regulatory expectations. Clinical trial designs that incorporate decentralized models, mobile research units, and expanded site networks help address enrollment gaps while strengthening the evidence base required for regulatory approval. However, these approaches place new demands on clinical supply chains, which must deliver investigational products reliably across complex and often unpredictable logistical environments.

Beyond any scientific or regulatory reasons, the issue of ethics in relation to equitable access to lifesaving therapeutics comes into play, which is why it is important to include hard-to-reach patients. Clinical trials help make lifesaving medications available to participants, which usually represent the best available treatment for these patients. This is particularly true for participants in underserved or deprived areas, where the standard of care may be nonexistent or, at best, limited. So, when trial participation is limited to areas near major research centers or health facilities, a significant portion of participants is left out. For instance, in a 2024 index by the Access to Medicine Foundation, it was determined that only 43% of clinical trials are conducted in low- and middle-income countries. This is even though these countries are home to about 80% of the world’s population. Moreover, market access strategies are often tied to where trials are conducted, meaning that countries omitted from the research phase may experience delayed drug availability, limited inclusion in reimbursement negotiations, and persistent gaps in treatment options. Such disparities underscore the ethical and scientific imperative of expanding global trial footprints to ensure equitable access and generalizable research findings.

Supply Chain As An Enabler Of Inclusion

Equitable trial access ensures that the burdens and benefits of clinical research are distributed more fairly across society. Patients from rural regions, underserved communities, or low-income countries should not be excluded simply because logistical barriers make participation more difficult. Ethical clinical research requires that sponsors actively address these barriers through thoughtful trial design and operational planning.

Supply chain infrastructure plays a critical role in enabling such inclusion. Without reliable mechanisms for transporting, storing, and administering investigational products in remote or resource-limited environments, the promise of equitable trial participation remains difficult to achieve. As such, clinical supply chains must evolve from purely operational functions into strategic tools that support inclusive research practices.

Reaching hard-to-access patients can have significant implications for global health outcomes. Many diseases with the highest global burden, such as infectious diseases, certain cancers, and neglected tropical conditions, are concentrated in regions with limited healthcare infrastructure. Conducting clinical trials in these environments not only expands access to potential therapies but also generates data that is directly relevant to the populations most affected by these conditions.

Incorporating these populations into clinical research also accelerates the development of interventions tailored to diverse healthcare settings. For instance, understanding how treatments perform in environments with limited refrigeration, constrained clinical monitoring, or variable patient follow-up can inform the design of therapies and delivery models better suited to real-world conditions.

Moreover, inclusive clinical trials contribute to capacity building in healthcare systems by strengthening local research infrastructure, training medical personnel, and fostering collaborations between global sponsors and regional healthcare providers. These benefits extend beyond the trial itself, supporting longer-term improvements in healthcare delivery and disease management.

In this context, the ability to design clinical supply chains that reach geographically isolated or operationally challenging environments becomes a key enabler of global health innovation. By overcoming logistical barriers to participation, sponsors can generate more representative clinical evidence while expanding access to potentially lifesaving therapies for patients who might otherwise remain excluded from the research ecosystem.

However, there are significant barriers that hinder the operations of clinical trials in hard-to-reach areas. These challenges include geographic barriers, limitations in infrastructure, regulatory complexity, uncertainty in forecasting and temperature-sensitive therapies.

One of the most significant challenges facing clinical trials in hard-to-reach areas has to do with access to the patients. Patients may be located in remote or rural locations with limited transportation. In some cases, investigational products may require multiple modes of transportation before reaching a patient. For instance, Rwanda and Ghana use small aircraft or drones to supply medical products to patients in hard-to-reach areas.

Operational Challenges And Innovative Solutions

In most geographic locations, clinical trials have to navigate a complex network of regulations surrounding the importation, storage, and distribution of investigational products. Each country may have certain requirements that are unique to them, requiring sponsors to prepare separate permits for each country under consideration. This can be cumbersome and time consuming. In contrast, Europe’s EMA has a standardized process for most of its member countries, which reduces this burden for sponsors.

A lot of regions outside the so-called developed countries lack the infrastructure required to support clinical trials. This is especially true for temperature-sensitive materials that may require special storage considerations, such as refrigeration. A lot of countries still grapple with electricity issues and may also lack adequate storage facilities. There is also the issue of not having enough experienced staff to handle the investigational medicinal products. In cases like these, the clinical supply chain planners must carefully work with the sites and coordinate the quantities to ensure the sites receive inventory they can manage effectively to minimize risks associated with temperature excursions and expiration of the product.

Forecasting uncertainty is an issue that bedevils most, if not all, clinical trials but the issue is exacerbated for trials that are targeting or including patients that are hard to access. Reasons include limited awareness, barriers to transportation, or the limited capacity of the site. For some trials, like rare disease trials, there is an extra layer of complexity as patients may be dispersed across different geographical areas. It is imperative for clinical planners to adapt their planning strategies to fit these scenarios.

Addressing these challenges requires clinical supply strategies that prioritize flexibility and resilience. Rather than relying solely on centralized distribution models, sponsors increasingly employ regionalized logistics networks that position investigational products closer to clinical sites.

Regional depots can significantly reduce transit times and mitigate the risks associated with long international shipping routes. By strategically placing inventory in geographic proximity to trial sites, sponsors can respond more quickly to fluctuations in patient enrollment while maintaining appropriate temperature control.

Advances in temperature-controlled packaging have also expanded the feasibility of conducting trials in challenging environments. Modern insulated shippers with extended thermal protection allow temperature-sensitive products to remain stable for extended transit durations without requiring active refrigeration.

Decentralized clinical trial models are another emerging strategy for reaching underserved populations. Telemedicine platforms, home nursing services, and mobile clinical units enable investigators to engage patients who might otherwise face significant travel barriers. This shifts distribution from site-centric delivery to patient-centric logistics.

Digital supply chain monitoring tools further enhance operational visibility. Real-time shipment tracking and temperature monitoring systems allow supply planners to detect potential disruptions and intervene before product integrity is compromised.

The Last Mile Challenge

While international logistics often receive significant attention during trial planning, the final stage of distribution, the last mile, remains the most vulnerable segment of the clinical supply chain.

Delivering investigational products from regional depots to remote clinical sites or directly to patients may involve complex local transportation networks with limited reliability. Poor road infrastructure, inconsistent courier services, and environmental factors may introduce additional risks.

Innovative last-mile solutions are emerging to address these challenges. In some regions, drone delivery systems have been used to transport medical supplies to isolated communities. Mobile clinical units equipped with temperature-controlled storage can deliver therapies directly to patients in remote locations. Partnerships with local healthcare providers or nongovernmental organizations can also help establish reliable distribution networks in underserved regions.

Ultimately, successful last-mile strategies depend on a detailed understanding of local conditions and close collaboration with regional logistics partners.

Strategic Supply Chain Design For Global Trials

Reaching hard-to-access patients requires clinical supply chains designed with resilience as a core principle. Sponsors must anticipate potential disruptions and incorporate redundancy into their logistics networks.

Maintaining safety stock at regional depots, establishing alternative shipping routes, and working with multiple logistics providers can help mitigate the impact of transportation delays or infrastructure failures. Risk-based supply planning approaches allow teams to identify the most vulnerable segments of the distribution network and develop targeted mitigation strategies.

Equally important is close coordination between clinical operations teams and supply chain planners. Real-time communication regarding site activation timelines, enrollment trends, and protocol amendments allows supply strategies to evolve alongside the trial.

As clinical research continues to expand globally, the ability to reach hard-to-access patients will become increasingly central to successful trial execution. Advances in digital monitoring technologies, decentralized trial models, and innovative distribution solutions are transforming how investigational therapies are delivered.

However, technology alone cannot solve the challenge. Effective supply chain design also requires a strategic mindset that places patient accessibility at the center of operational planning. By building flexible, resilient logistics networks capable of operating in complex environments, sponsors can expand trial participation while ensuring that investigational therapies reach patients safely and reliably.

In doing so, clinical supply chains become more than logistical support functions; they become essential enablers of inclusive and globally relevant clinical research.

About The Author:

Jonathan Naab is a clinical supply chain professional and biotechnology specialist with more than five years of experience supporting global clinical trials across oncology, virology, hematology and general medicine. Naab has led end-to-end supply planning, forecasting, IRT setup, material transfers, and cold-chain distribution across 50+ global sites, helping achieve over 98% on-time delivery and supporting pivotal programs such as LUMAKRAS. He is currently pursuing a Ph.D. in Business at the University of the Cumberlands and holds a Master of Business & Science from Keck Graduate Institute. His work bridges biotechnology, operations, and patient-centered access in clinical research.