We are living in a golden age of orphan drug development, with new targets, candidates, and treatments offering fresh hope to people who may previously have felt forgotten. While the root cause is advances in technology and medical understanding, the emergence of decentralized and hybrid clinical trials has played a huge role in getting innovative, life changing medicines through the pipeline and to the people who need them as soon as possible. 
 
As we mark the 15th international Rare Disease Day, other therapy areas are well on the path to applying the sub-sector’s approach to their own portfolios. But, as with all transitions, the move from traditional to modern research must be managed carefully.
 
The key to “having it all”, from faster recruitment, higher retention, and increased participant diversity to high levels of patient protection and data quality, is maintaining connections, providing support, and enhancing transparency across stakeholders. 
 
In short – success relies on making sure we take everyone along for the ride. 
 
The future is hybrid
The potential benefits of decentralized methods, in which some or all site visits are replaced with remote data collection, have been well documented. 
 
In the rare disease space, where eligible study participants are few and far between, this model has been boosting recruitment and accessibility for some time. And since 2020, when COVID-19 resulted in travel restrictions and social distancing measures, other therapeutic areas have increasingly been following suit. The intervening years have built an evidence base on how this evolution of methods can drive trial efficiency and patient centricity – and demonstrated that the future is hybrid. 
 
We now know that the majority of studies will be unsuited to pure decentralization, as most protocols will require at least some face-to-face participant/site interaction. In addition, a European Medicines Agency (EMA) recommendation paper on decentralized elements in clinical trials, published in December, advised that sponsors maximize accessibility by giving all participants the opportunity to visit sites, should they wish. 
 
But knowing the direction of travel isn’t enough to arrive at the destination. If we, as a sector, are to squeeze every drop of potential from the hybrid trials model, we need to identify and address the challenges presented by this transformative shift. 
 
Supporting the participants
A significant proportion of hybrid trial benefits are clustered around the theme of patient centricity, such as boosting recruitment and retention by reducing participant burden and improving patient engagement in the protocol. 
 
Central to this is choice. In some circumstances, people may prefer to travel to a site for their appointments, as set out in the EU DCT recommendation paper.  Additionally, some potential participants may not live in an environment where it is safe and effective to conduct study procedures.  It is important to remember that not providing a bricks and mortar option, or other locations for in-person visits, would effectively exclude them from the study. Luckily, where site visits are required or desired, the technology exists to make their trip as easy as possible. Advanced travel concierge services can provide a comfortable, stress-free journey, whether it is 12 minutes or 12 hours, and specialist expense reimbursement solutions ensure participants are not left out of pocket. 
 
We also need to be cognizant of the fact that remote data collection, through home health visits or wearables and sensors, runs the risk of eroding the link between investigators and participants. This lack of communication can have a huge impact on trial retention. If people are not kept “in the loop” they can feel unappreciated or disconnected from the study, which can lead to dropouts and, consequently, missed data points. Maintaining this vital connection by enabling two-way conversation between the site and the participant, and by ensuring home health teams have all the information they need to answer questions and provide updates, can help sidestep this potential pitfall. 
 
Supporting the sites 
A key stakeholder that is often forgotten in the shift away from 100% physical trials is the site. Investigators, who are ultimately responsible for patient safety, can be confused about their regulatory commitments, wary of losing oversight to home health teams and are often frustrated with the sheer volume of different technologies and solutions sponsors may ask them to engage with. 
 
Allowing sites to review or interview healthcare professionals (HCPs) before appointment, and fostering relationships, via face-to face meetings or in-person HCP training, for example, can provide important reassurance. Site teams could also join visits virtually using an established telehealth system, to increase their comfort levels and provide some more tangible continuity of care for the participants.
 
When attempting to reduce the burden on sites, sponsors can look for partners who provide seamlessly integrated solutions. When services such as participant support, home health, travel and reimbursement, and meetings management are all operated through the same platform, it streamlines administration processes. This makes life easier for sites on a practical level, reducing the number of moving parts they are expected to track.
 
Supporting study design 
In the shift to hybrid, preparation remains one of the most important considerations. Every decentralized element of a study needs to be embedded into the protocol from day one. That means ensuring that the type of sample collection and measurement are suited to the home setting and that visiting HCPs have everything they need to do their job. The alternative is frustrating and expensive protocol amendments and delays. 
 
Getting it right first time relies on effective communication between all sites, partners, and providers. Open dialogue between central laboratories and home health teams, for example, allows for seamless lab manual development, HCP training and remote sample collection processes from the outset. Direct lines of communication between the two and sites will also help avoid in-study delays connected to queries.
 
Emulating success
Hybrid trials have huge potential to drive change by making research more efficient, more patient centric, and less burdensome for sites and participants, while still prioritizing safety and high-quality data collection. 
 
Trials in the rare disease space over the last decade have shown us that it is possible. Emulating that success will rely on our ability to view this new model as a team sport and implement the frameworks and processes we need to all move forward together.