By Marcelo Vaz, Vice President of Medical Services at TMC
Rare disease clinical trials face unique challenges that demand innovative solutions. With patient populations that are both small and geographically dispersed, traditional trial models often create insurmountable barriers to participation.
The journey of rare disease patients is arduous long before any clinical trial begins. Diagnosis is frequently delayed as many physicians may not immediately consider rare conditions. By the time a diagnosis is confirmed, patients have often experienced a lengthy and traumatising process, forming strong bonds with the specialists who finally identified their condition.
However, these specialist centres — often the only locations qualified to treat and conduct clinical trials — may be hundreds of miles from a patient’s home.
Although rare disease patients tend to be highly engaged with studies that might offer treatment for previously untreatable conditions, traditional study designs frequently attempt to extract maximum data during site visits, leading to exhausting day-long appointments after hours of travel.
Even seemingly minor considerations, such as fasting requirements for morning tests, might necessitate overnight accommodation for travelling patients, turning a single visit into a multi-day commitment for both patients and their caregivers.
When we talk about essential care and visiting a site hundreds of miles away once or twice a year, that is one thing. However, when we start talking about a clinical trial requiring weekly or monthly visits, this becomes a significant hurdle.
This is where decentralised clinical trials (DCTs) and patient-centric approaches offer a promising path forward — not as afterthoughts but as foundational elements of trial design.
Balancing connection and burden with a hybrid approach
In the wake of the COVID-19 pandemic, regulatory attitudes towards remote trial elements have shifted dramatically. What was once viewed with scepticism is now recognised as an essential component of modern clinical research.
DCTs offer a transformative solution to the challenges of conducting clinical trials for rare diseases.
By bringing trial procedures to the patient’s home or local community, DCTs have the potential to significantly reduce the burden of frequent, long-distance travel. This approach increases patient convenience and broadens the potential pool of participants, ensuring that even those in remote or underserved areas can participate.
Although decentralised elements often require substantial upfront investments in technology, home nursing and system setups, the value of the human element cannot be ignored. While the cost of the trial itself may be higher, in the long run, it may become cheaper as DCTs can improve enrolment rates and reduce dropout rates — potentially accelerating study timelines to bring the treatment to market sooner.
DCTs increasingly open up access to potentially life-changing treatments for patients who would otherwise be excluded due to geographical or physical limitations.
However, while the theoretical benefits of decentralised trials are clear, practical implementation requires careful planning. The logistics of DCTs can be complex, particularly when the trial involves interventions that are not easily administered outside a traditional clinical setting, such as intravenous infusions or specialised diagnostic tests.
Country selection also becomes even more critical when planning decentralised elements, as regulatory frameworks, telemedicine regulations and home nursing availability vary significantly across regions. The variability in service provision between regions is particularly challenging when rare disease patients are already scattered across multiple locations.
Taking into account the variability between countries and solutions, a hybrid approach — combining on-site and remote visits — is likely to be the optimal model. This approach reduces the burden on both patients and sites while maintaining the crucial patient-clinician relationship that is often vital for these vulnerable populations.
With hybrid models, critical efficacy and safety evaluations and procedures that require specialised equipment can still be conducted at a central location or reference centre. At the same time, routine follow-ups, data collection and even some assessments can be performed remotely.
Technology plays a crucial role in making hybrid models viable, reducing the burden on patients while maintaining data integrity and safety monitoring. For example, modern portable spirometry devices allow patients with respiratory conditions to perform tests at home while being guided remotely by a clinician who can view the results in real-time. Similarly, point-of-care testing enables critical safety labs to be conducted in the patient’s home, with results available immediately.
Nonetheless, technology should serve as a facilitator rather than the focal point. The goal is not to embrace technology for its own sake but to harness it in ways that genuinely improve the patient experience and clinical data quality.
Achieving patient-centricity across multiple disciplines
Central to the success of DCTs and hybrid trials is the principle of patient-centricity by design: incorporating these considerations from the earliest stages of protocol development rather than attempting to retrofit decentralised elements into a traditional design.
This approach requires asking fundamental questions in addition to the traditional medical or scientific ones. Can certain tests be performed at home, and are all proposed tests necessary? Are remote data capture methods validated, and are the necessary resources available where patients are concentrated? Lastly, how will patients and caregivers perceive the study?
In practice, this means engaging with patients, caregivers and advocacy groups long before the trial commences. By soliciting feedback on the impact of visit frequency, procedure scheduling and remote assessment feasibility, sponsors can design trials that better fit participants’ real-world needs with minimal disruption to their lives.
Rather than being an afterthought, patient-centricity must be a foundational element that shapes every decision in the trial design process, allowing studies to become more accessible, more humane and more effective.
Successfully implementing patient-centric designs requires collaboration across multiple disciplines. Clinical operations must assess feasibility, while regulatory experts must navigate country-specific requirements. Medics, statisticians and investigators then need to validate the scientific integrity of the approach. Patient advocacy groups should also provide insight into acceptability.
In rare disease research, where every patient counts and traditional trial designs often fall short, this multidisciplinary approach to creating hybrid, patient-centric trials is not just good practice — it is essential for expanding treatment access for some of our most vulnerable patient populations.
This article first appeared in Life Sciences Review Europe.