Equity in rare and genetic disease clinical trials is both a scientific necessity and an ethical responsibility. Unlike patients with more common conditions, those living with rare diseases often face longer diagnostic journeys, fewer treatment options and limited access to specialty care and clinical research trials. With these challenges, it is critical that rare disease patients and families can benefit from medical innovation leading to potential treatments. Advancing equity requires tailored, patient-centered approaches that reflect health care system infrastructure, as well as cultural, geographic and socioeconomic realities. Community-based site networks, thoughtful application of digital technology, flexible study designs and inclusive protocols are key to enabling broader participation in rare disease clinical trials. Sustained collaboration across industry, academia, regulators and advocacy groups can ensure that no patient is left behind in the pursuit of treatment and discovery.
Redefining equity in the rare disease context
Before we can address equity in rare disease clinical research, it’s essential to clarify what equity means — and how it differs from equality. While equality treats everyone the same, equity recognizes that people start from different places and have different needs. It’s about removing systemic and situational barriers to provide everyone with a fair opportunity to achieve the best outcomes.
In the context of rare diseases, equity means ensuring that all patients — regardless of how rare the disease is, where patients live, their socioeconomic background, or their cultural or genetic identity — can receive a timely, accurate diagnosis, access expert care and, most critically, the opportunity to participate in clinical trials. For patients (and caregivers) living with a rare disease, trial enrollment isn’t just an opportunity to contribute to research — it may be their only chance to receive life-changing treatment.
Yet, achieving equity in rare disease trials is uniquely challenging. Small patient populations, geographic dispersion, inconsistent and cumbersome access to care, and a lack of disease awareness further complicate recruitment and retention in a clinical trial. These challenges demand a proactive and tailored approach from day one. Protocols must be built not just around the scientific details of the disease, but around the lived realities of the patients. Everything from patient and caregiver concerns, geography, local resources, and income to culture, age, religion, and more must be factored in.
The landscape of inequity in rare disease research
Rare diseases may each affect only a small number of individuals, but collectively they impact more than 300 million people worldwide — spanning about 10 distinct conditions. Many of these diseases are degenerative, disabling or life-threatening, with a large share affecting children. For the vast majority, no approved treatment exists.
Beyond the physical toll, patients and caregivers often face stigma, isolation and a health care system that is ill-equipped to support them, particularly at a local level. Limited disease knowledge and a lack of clinical expertise compound these challenges, making accurate diagnoses and effective care difficult to access.
The resulting inequities in rare disease research and care stem from multiple systemic issues — including diagnostic delays, limited access to medical specialists, trial access burdens, infrastructure gaps, lack of treatment comparators, and cultural or religious constraints. Each represents a distinct but interconnected barrier to equitable participation and outcomes.
The diagnostic divide
Patients with rare diseases can be found in all corners of the world. They may live in urban, suburban, rural, affluent, middle- and low-income, or minimally populated areas. Often the first challenge they face is getting a timely and accurate diagnosis of their condition. Indeed, diagnostic odysseys are commonplace, particularly in under-resourced locations, owing to lack of access to specialists capable of identifying rare diseases.
Even when specialists are available, the wait list is long, or information about specialists’ availability is limited, and it can take years to receive a correct diagnosis. In addition, local laboratories, particularly in underserved areas, may not be equipped to conduct genetic sequencing and other advanced tests required to correctly diagnose rare diseases. Biological samples may need to be sent to western European countries or the U.S., which requires compliance with special customs requirements that are difficult to meet.
Even in high-income countries, patients outside major urban centers may need to travel long distances to reach a center of excellence. In many parts of the world — particularly outside the U.S., Europe, the UK, Canada and Japan — centers are very sparse.
The problem of incomplete genomic databases creates additional diagnostic difficulties. Much of these data are generated through various population-based studies that are not inclusive of racially and ethnically diverse populations. The lack of full representation of the genomic information for numerous populations in such databases used for diagnostic purposes contributes to misdiagnoses and missed diagnoses –– an additional barrier to building a greater understanding of rare diseases.
Trial access burdens and eligibility barriers
It is important to note that even access to a clinical trial presupposes a certain privilege. Only a fraction of rare diseases have active clinical trials, often those supported by strong advocacy or higher visibility. Most rare conditions remain without trials, leaving many patients without even the chance to participate — a deeper layer of inequity that compounds the challenges rare disease patients face.
For those patients lucky enough to obtain a rapid and accurate rare disease diagnosis and have the potential to participate in a clinical trial, finding a way to take part can present a hurdle. Patients are often widely dispersed, but there are a limited number of treatment facilities that can conduct rare disease trials, making it burdensome for patients to reach those locations.
Most trials are conducted at academic/tertiary care centers located in large cities, requiring many rare disease patients to travel long distances. Business hours for assessment appointments can be a barrier for caregivers and families due to costs and school and work commitments. Lack of available support for rare disease patients and caregivers creates unique concerns and ongoing needs. The cost and other logistical burdens associated with the need to travel can greatly reduce trial participation, even in well-resourced countries.
In addition, local family and general practice physicians and nurse practitioners are often not as informed about current information regarding rare and ultra-rare diseases. Primary care practices may not have sufficient resources or advanced technologies available for faster diagnosis and treatment options. These challenges can be further complicated for under-resourced communities, where awareness of specialty care and the availability of practitioners versed in understanding the diverse needs of affected individuals is more limited.
Infrastructural and global disparities in the health care system –– combined with lack of knowledge of rare diseases and existing diagnostic criteria, inadequate access to treatments and uncoordinated and limited access to research resources for discovery and drug development efforts –– result in sparse data collection and low diagnosis rates that broaden the gaps in knowledge for a given disease and further exacerbate existing disparities.
For instance, patients and physicians may find that lack of publication of research results on specific genetic tests or gene mutations can lead to exclusion from a clinical trial that may involve the only therapy available to them. This issue arises most often for patients with ultra-rare diseases for which multiple variants of the relevant gene may exist. Researchers can only know about those variants published in the literature. Thus, trial protocols may not specify newly identified gene mutations. Due to the strict inclusion criteria, patients with genetic mutations that are not well defined cannot participate, which hurts the patients and is problematic for the trials themselves, because every patient matters.
Comparator disparities
In some regions country-level regulatory guidelines may pose a barrier, as patients are excluded from trials simply because the approved comparator treatment is not available in that country. These standard-of-care therapies, used in blinded arms to assess new drug efficacy, may be unavailable or unaffordable in certain countries.
As a result, otherwise eligible patients are left out, and valuable data from diverse populations is never captured. Sponsors, drug/device manufacturers and contract research organizations (CROs) must work with health authorities and regulators to close this gap — whether through supplying comparator drugs directly or designing more inclusive protocols.
Cultural and religious considerations
Equity also requires cultural competence. Some rare diseases are concentrated in specific populations due to cultural, familial or genetic factors, requiring thoughtful, culturally competent localized recruitment strategies.
Religious beliefs can shape how patients engage with the health care system in general and with clinical trials specifically. For example, members of the Amish or Mennonite communities may decline injectable therapies but accept oral medications. Some groups avoid air travel altogether, necessitating ground transportation and home visit options.
These considerations aren’t peripheral — they’re essential. Understanding and respecting them makes the difference between inclusion and exclusion.
Solutions in practice: Equity in rare disease research requires flexibility, cultural competence and intentionality
Addressing the challenges rare disease patients face and bringing equity into rare disease research requires knowledge about local and country-level regulations, health care system infrastructure and customs, as well as a collaborative approach among all stakeholders, including patients and their caregivers, clinicians, researchers, research institutions, regulatory authorities, patient advocacy groups, pharmaceutical companies, CROs, and clinical trial sponsors.
Together, these stakeholders must foster a clinical trial environment that is not only scientifically rigorous but genuinely patient-focused. That starts with inclusive protocol design — built around the real-world needs and concerns of patients — and extends to long-term collaboration among sponsors, CROs, investigators and advocacy organizations.
Equity also depends on structural investments: expanding regional infrastructure, leveraging technology, empowering community-based sites and training health care professionals to recognize and address rare diseases in diverse populations. Equally important is the continued evolution of regulatory guidance — grounded in both scientific integrity and a clear commitment to inclusion.
Designing for the real world
The first step toward equity in rare disease research is ensuring that all patients — regardless of geography, background, or health care access — have a more streamlined path to accurate diagnosis. From there, it’s critical to design clinical trials that meet patients where they are, minimizing burden and building protocols around outcomes that truly matter to them.
That means crafting studies that reflect the lived experiences of patients and caregivers — as well as the biological realities and heterogenicity of the disease. Flexibility and coordination of care are essential. Telehealth options, home or community-based visits, mobile labs, and digital tools can make participation possible for those who might otherwise be excluded.
Minimizing patient burden and addressing their key concerns aids in patient recruitment and retention. Providing ongoing support focused on patient and caregiver needs and concerns also enhances retention, which in turn facilitates the collection of vital data for primary endpoints, ultimately leading to accelerated approval of new treatment options.
Ethical design is also fundamental. Placebos should be avoided in situations where doing so would deny patients a known standard of care. When appropriate comparator treatments exist, they should be offered in blinded fashion to ensure every participant receives active support, while still maintaining scientific rigor.
CRO and sponsor collaboration
Close collaboration between sponsors, patients, caregivers and CROs from the earliest planning stages ensures that equity is prioritized in the trial design from the beginning. But partnership alone isn’t enough. Regulators and patient advocacy groups also need to be at the table to shape protocols that are both scientifically sound and patient-centered.
That means elevating the patient voice, understanding evolving regulatory expectations, genetic variation and clearly defining the roles and responsibilities of each stakeholder. For example, when comparator drugs are required, it’s essential that sponsors provide them — even when they add additional and sometimes significant cost to clinical trial budgets — to ensure equitable access and valid data. Country-level health authorities must also be involved so that standard-of-care treatments can be made available for patients in their jurisdictions.
Logistical barriers should also be addressed upfront. Travel costs, caregiver accommodations and other patient expenses must be factored into trial budgets. CROs, in turn, must ensure that all staff — including those managing decentralized and virtual components — are equipped with the specialized knowledge rare disease trials demand. Disease-specific training, as well as training in patient diversity and cultural competence, isn’t optional; it’s required for success.
Infrastructure investment and regional expertise
For families affected by rare diseases, everyday life leaves little time or energy to seek out clinical trial opportunities — especially when those opportunities are concentrated at academic centers far from home. Expanding access means meeting patients where they are. That starts with building community-based site networks that go beyond traditional hubs to reach underserved areas and overlooked populations.
These networks do more than bring trials closer to patients. They also equip local health care providers — including general practitioners and community physicians — with knowledge about clinical research and rare diseases they might otherwise never encounter or recognize. This outreach is essential for timely diagnosis, referral and enrollment.
The PPD™ clinical research business of Thermo Fisher Scientific takes seriously the critical role CROs play in expanding rare disease awareness and access. Through targeted education initiatives, we raise awareness of clinical research, illuminate the specific challenges of rare diseases, and increase visibility into how these conditions disproportionately affect certain ethnic and geographic populations. By sharing knowledge and supporting diagnostic capacity, we enable growth in the pipeline of specialists who are able to care for rare disease patients in underserved regions.
Equally as important, our global and regional teams include regulatory experts who understand both the formal frameworks and the logistical, linguistic and cultural dynamics that shape participation. These on-the-ground insights makes it easier to enroll and retain patients respectfully and effectively.
Engaging advocacy and education
Driving equity in rare disease research depends not only on building infrastructure — but on building trust, awareness and shared knowledge. That starts with sustained collaboration with patient advocacy groups and community organizations.
These groups are typically the first — and sometimes only — touchpoint for families navigating rare disease diagnoses. Engaging them early raises awareness about clinical trials, dispels misconceptions and connects patients to potential treatment opportunities. We have prioritized establishing research site networks in diverse, non-traditional regions to support rare disease education at the community level and increase participation in trials that might otherwise feel out of reach.
We also prioritize equipping health care professionals and investigators with the tools they need to approach rare disease research through an equity lens. Ongoing training on inclusive recruitment, cultural competence and the unique diagnostic challenges rare disease populations face is a baseline responsibility for both sponsors and CROs.
Evolving regulations, sustaining commitment
Over the past four decades, the global recognition of rare disease research has steadily grown — marked by key policy milestones. The U.S. Orphan Drug Act of 1983 laid the foundation, followed by the European Union’s regulation on orphan medicinal products. More recently, rare diseases were included in the United Nations’ 2019 Political Declaration on Universal Health Coverage and the 2021 Resolution on “Addressing the Challenges of Persons Living with a Rare Disease.” In 2024, rare diseases appeared for the first time in the World Health Organization’s Fourteenth General Programme of Work.
In parallel, regulatory guidance has evolved to address the unique complexities of rare disease trials. Agencies around the world now recognize the need for flexible approaches that uphold data integrity while ensuring patient inclusion. These guidelines are not just about operational frameworks — they reflect a scientific imperative. Medications often behave differently across populations. Without diverse participation, our understanding of safety, efficacy, and therapeutic value remains incomplete.
As global regulatory landscapes become more nuanced, CROs must stay abreast of change. That means going beyond therapeutic expertise to include deep regulatory fluency — with teams that understand not only current policies, but the trends shaping tomorrow’s expectations. Sponsors rely on partners who can anticipate requirements across multiple regions and translate that foresight into smarter, more inclusive trial design.
What’s next: A vision for equitable rare disease research
Despite growing momentum, rare disease clinical trials still exclude too many people — individuals living with lifelong, debilitating, and potentially fatal conditions. The need for a more equitable future is urgent, and the path forward depends on broad, sustained collaboration. Difficult-to-enroll studies stand to benefit from the leadership of experienced, cross-functional rare disease teams, innovative trial designs and globally distributed site partnerships.
One-size-fits-all approaches won’t work. Each therapeutic area demands its own tailored strategy, and even within a single disease, different patient communities may require distinct engagement models. Cultural and religious considerations, logistical realities and historical mistrust must all be taken into account. Community-based participatory research — conducted in partnership with patients, investigators and local organizations — enables these barriers to be identified and addressed while reducing unconscious bias in protocol design.
The diagnostic journey must also be reimagined. For patients far from centers of excellence, advanced testing remains largely inaccessible. Solutions like genetic testing and genomic screening, sequencing and genetic counseling across diverse populations and communities — coupled with early intervention — can dramatically reduce time to diagnosis and connect patients with life-saving therapies sooner. Public policy and payor support will be key to expanding access and ensuring that underrepresented populations are no longer left behind.
Local physicians and healthcare providers must be better equipped to recognize, diagnose and refer patients with rare diseases. At the same time, investment in infrastructure — both physical and digital — is critical to enabling equitable trial participation and accelerating research.
CROs play a central role in this future. By raising awareness, sharing information and data transparently, and embracing digital innovations, we can drive progress across geographies and disease areas. These efforts should be supported by harmonized global regulatory frameworks, deeper alignment across patient advocacy groups, and strengthened partnerships between CROs, sponsors, investigators, and regulators.
Ultimately, advancing equity in rare disease research is about more than improving clinical trials — it’s about reshaping the system to serve all patients, everywhere.
Conclusion: Equity is a prerequisite for rare disease progress
Equity in rare and genetic disease research is a moral obligation and scientific necessity. Without it, we risk missing critical data, delaying discoveries and leaving entire communities behind. Progress depends on collective action: sponsors, CROs, investigators, patient advocates, and regulators must each do their part to close long-standing gaps in diagnosis, trial access, infrastructure and education.
For sponsors, choosing the right partner is essential. A CRO with deep rare disease expertise; global regulatory fluency; an expansive site network across regions like Europe, the Americas, the Middle East, Africa and Asia-Pacific; and a track record of patient-centered design and scientific rigor can help transform intent into impact. When that partnership is grounded in shared values and a commitment to long-term investment, the benefits extend beyond the trial — reaching patients, families and entire communities.
The path to equity is not without obstacles. But by working together, we can dismantle the barriers rare disease patients too often face — and accelerate the delivery of innovative therapies to those who need them most.