Unlocking the potential in rare disease research with decentralised trials

A survey by rare disease patient network Raremark found that 86% of the community members asked were interested in taking part in clinical trials. CEO Jeremy Edwards looks at how decentralised trial models can solve some of the challenges for clinical trial recruitment in rare disease.

With low and geographically dispersed patient populations in rare disease, deciding where best to place trial sites can be a headache for sponsors. Sites need to be close enough for travel, and the number of site visits and trial appointments must also be manageable for people living with the complications of having little-known and rarely-researched orphan diseases.

Decentralising trials, a topic revitalised by the COVID-19 pandemic, seems like a no-brainer, but would people with rare diseases be open to them? In fact, how do rare disease patients even feel about clinical trials? A survey of members of the Raremark community found that 86% of respondents were interested in taking part in a clinical trial now or in the future.  The people who took part were from across the world, living with hemophilia, idiopathic pulmonary fibrosis, myasthenia gravis, and sickle cell disease.

Research and development will always be important to rare disease patients

This finding may come as a surprise to anyone who read this CISCRP report last year. The report found that people’s willingness to take part in clinical trials in 2020 fell dramatically compared to previous years – however that survey was conducted with the wider public while the Raremark survey focused specifically on people with rare diseases.

Progress in research and development for better treatments will always be a priority for rare disease patients. There are around 7,000 known rare diseases and only a fraction of those have treatments available.

“For those participants that did not want to take part in a clinical trial, reasons given included not knowing where to start looking for information as well as the COVID-19 pandemic, hesitance about traveling and not wanting to disrupt their medication plans.”

Getting a diagnosis is not always easy; people have to battle many years because rare diseases are not as extensively researched or known about as more common ailments. Common experiences heard from people with rare diseases can be things like:

“It took me a full 10 years [to get a diagnosis]! I experienced my first symptoms when I was 12, they progressed at 13 and I got a correct diagnosis at 22.”

“No one ever knows what to do with you! It’s a pure guessing game!”

“Never heard of it before my mum was diagnosed, also nothing was actually explained to us, we found out most information on the internet!”

“I had to suffer hours of excruciating pain before I could be taken seriously.”

This illustrates the toll that having a rare disease can have on the individual and their family’s lives. This is a key reason why patients view the continued progress of research and development as important. For those participants that did not want to take part in a clinical trial, reasons given included not knowing where to start looking for information as well as the COVID-19 pandemic, hesitance about traveling and not wanting to disrupt their medication plans.

Positive patient feedback for decentralised trials

While the idea of decentralised and virtual trial methods – i.e. taking the trial to the patient, rather than the patient to the trial – has been a topic of interest for some time, COVID-19 has brought it to the forefront.

Investment into companies that offer decentralised and virtual trial solutions increased dramatically in 2020 and this is translating into practical discussions regarding the implementation of decentralised trials. With all of this in mind, Raremark was interested to learn what people with rare diseases think about them.

We asked people where they would prefer to receive their trial medication and monitoring appointments if they decided to take part in a clinical trial. 57% of participants said they would like to receive the trial medication through a mix of clinic, home, and nearby hospital visits, and 45% would like the same mix for how they are monitored during trials.

Only a few people surveyed said they wanted to have all their appointments only at the clinic or only at their home.

We also asked participants if they would have any concerns about taking part in a trial that would not require them to travel to the clinic for all their appointments – 87% of survey participants expressed no concerns about this approach to trials.

When asked about features of decentralised trial designs that people found most attractive, the top reasons given were the convenience of having more of the study take place at home and less time traveling, as well as the use of technology, both to communicate with research staff and to have their health monitored.

For the 13% of participants who did have some concerns about these types of trials, the reasons they gave for their reservations included possible adverse reactions to the drug, and not having specialists there to help them. A few others said they would struggle to comprehend all the trial literature on their own.

What does this mean for clinical trials in the future?

The COVID-19 pandemic has turned many aspects of clinical research upside down; however it will also be a powerful agent for change in the way the pharma industry conducts clinical trials. One of the barriers to uptake of virtual trials in the past has been the assumption that it requires a fully decentralised approach. We’re now seeing a shift in focus towards hybrid models where sponsors identify aspects of a trial that could be done virtually or at locations closer to patients’ homes.

Clearly, face-to-face visits will still be necessary, but through a decentralised approach these can be limited and balanced with home visits from nurses or by engaging local clinics and hospitals so some appointments can be conducted at the patient’s regular doctor’s office.

There are already tools available and more being developed that can help make decentralised trials a possibility, including software that capture patient consent easily, at home video consultation tools that make staying in contact with patients straightforward, apps for nurses to use when they’re making home visits, and even integrated wearable devices that collect the relevant data needed for a trial such as biomarker data, physical activity and motor symptoms.

Adopt a person-first approach to increase engagement and retention

The best way to keep people engaged in trials and reduce trial dropouts is taking a person-first, approach.

It is essential to remember that the people who take part in clinical trials may have jobs, work or childcare commitments, or the nature of their disease may mean certain tasks take priority over others.

To keep people living with rare diseases engaged, clinical trials must adapt to fit as seamlessly as possible into people’s lives. Decentralised and hybrid trial models can help by removing obstacles that people may find disruptive to their everyday life when taking part in a trial, such as the burden of traveling to trial sites multiple times.

Additionally, there are several ways to keep the people who opted to participate interested and engaged, whether a decentralised approach is adopted. These include access to information and keeping communication lines open before, during and after a trial.

Participants should always feel comfortable asking questions and voicing concerns, so it is important to use every opportunity to keep people informed and treat their time and commitment with respect.

A few simple ways to achieve this include:

  • Replying to patient emails and call-backs promptly – there’s nothing worse than spending lots of time looking for patients only to lose them because of a missed call
  • Catering for work schedules, planning calls and screening appointments accordingly – remember patients have lives too.
  • Addressing any anxieties patients and caregivers have, including coming off existing medication, as well as questions regarding the trial drug or the tests and procedures involved in the trial.


Shifting towards decentralised trial designs can help solve some of the challenges around recruiting patients for orphan drug trials. Designing trials where participants do not have to travel as often and where some appointments can be done virtually will make them more convenient and cause less disruption to people’s lives. Rare disease patients are open to these trial types but still need some in-person appointments, therefore a hybrid approach with a mix of in-person and virtual appointments is desirable.

Ultimately, by understanding the world that rare disease patients are living in and designing trials accordingly, sponsors can significantly improve clinical trial engagement and participation.

You can learn more about our findings and the opinions around clinical trials in rare disease here.

About the author

Jeremy Edwards is the CEO of Raremark. He has been focused on aiding the biopharmaceutical and health sciences industry in the development of key compounds and new therapies for over 25 years.  His background includes executive leadership positions across the clinical development continuum; from full-service CROs, to highly specialised imaging modalities, to niche patient-focused service providers.