Today, less than 5% of the more than 7,000 rare diseases have an effective treatment. As such, continued research into rare disease remains imperative. Fortunately, recent years have seen increased impetus in orphan drug development spurred by several national and international programs. Launched by the European Commission and the US National Institutes of Health, the International Rare Diseases Research Consortium (IRDiRC) is one example. IRDiRC is committed to contributing to the development of 1,000 new therapies by 2027 and is focusing on rare diseases without currently approved treatments.

Meanwhile, incentives for orphan drug development provided under the US Food and Drug Administration’s Orphan Drug Act are succeeding. In 2023, GlobalData reported that over half of the novel drugs approved by the FDA in 2022 had an orphan drug designation. 

For progress to continue, the industry must address issues in the clinical trial space, and rare disease research is plagued by several. A lack of established endpoints and the often progressive and life-threatening nature of most of these diseases have become two key stumbling blocks. In addition, many countries will have only a few specialized clinics capable of serving as study sites for individual rare diseases. With 85% of rare diseases affecting fewer than one in a million people, the lack of available patients near sites has become one of the biggest impediments to these trials. 

It is neither fair nor feasible to expect a rare disease patient (approximately half of which are children, and many of which experience life-debilitating symptoms) to travel across the country for a study visit. When following the traditional trial model, small and nonrepresentative sample sizes are one of the most significant hurdles to running a successful rare disease trial.

Bringing trials to patients

The good news is some much-needed change is afoot. Interest in the decentralized clinical trial (DCT) model – which brings some or all study activities directly to the patient – has jumped since the pandemic, and many are looking at DCTs as the solution the rare disease community needs. The idea is not to eliminate clinical sites entirely but rather to extend them into the patient’s home in order to reduce the burden of participation and thereby recruit and retain more patients in the study.

“If you’re looking at a small subset of patients and they’re dispersed throughout the globe, there is probably a very small number of key principal investigators working in a small number of sites, and patients are going to have to come from quite far away to participate in any trial at all,” summarizes Ellen Weiss, former Vice President, In-Home Solutions for PCM Trials and well-respected industry expert in DCT strategy. “If we can have them diagnosed and perhaps screened and consented at the site and then continue the trial from home, everybody wins.”

According to GlobalData figures, this kind of model is starting to take off. As of 18 December 2023, the Clinical Trials database showed a total of 2,030 rare disease trials that have used components of decentralization so far, including ongoing trials. The chart below shows the most common types of decentralization in rare disease trials, with mobile healthcare – defined as the provision of healthcare services e.g. medical care, nursing, therapy, and monitoring directly at a patient’s residence – the most frequently used component.

While this includes telemedicine, mobile visits from a certified mobile research nurse (CMRN) are an important part of this. Such visits can be used to facilitate treatments that cannot be done virtually. A face-to-face visit from a nurse can also be instrumental in providing the support needed to keep patients and their carers engaged with the trial and in compliance with the protocol. In a trial involving highly vulnerable and often pediatric patients, this level of care can be critical to the success of the study.

Mobile visits and rare diseases

Mobile visits are an invaluable addition to any trial, but they are emerging as a key enabler of remote rare disease research. According to GlobalData’s database, the five most common therapy areas for rare disease trials with mobile visits are infectious disease, oncology, hematological disorders, central nervous system, and metabolic disorders.

Since 2003, 23% of all trials with mobile visits in GlobalData’s Clinical Trials database have studied a rare disease. The average for trials that use other aspects of decentralization (but not mobile visits) is 16%. This suggests in-person visits to a patient’s home or location of choice are being recognized as an important element in a decentralized rare disease trial, while a reliance on web and mobile-based technologies may be less suitable.

Of all the rare disease studies that utilized mobile visits, almost a third (32%) are currently ongoing. These kinds of protocols are on the rise, growing at a rate of 700% from 2006 to 2023.

2021 was the record year for new rare disease trials with mobile visits. While growth has now steadied, GlobalData’s Managing Analyst Scotty Chung-Siu expects it to continue. “I do believe COVID-19 has shown many sponsors the benefits of DCTs such as home nursing/mobile visits,” he adds.

Rare diseases currently represent over 30% of the protocols supported by mobile research company PCM Trials. “Sponsors are also now asking PCM Trials to add more international locations in the trials they are serving,” says Weiss. “For example, a sponsor with trials in a rare musculoskeletal disease has added home visits for subjects in several additional countries. This new footprint is much broader than trials we envisioned just a few years ago. Added geographies include Baltic, Eastern EU and African countries to broaden the trial’s reach. We expect this to continue into 2024 and beyond, across more sponsors active in rare disease. PCM Trials is ideally positioned to serve."

Mobile nurses in action: Rett Syndrome

To consider the importance of mobile visits to rare disease research in more detail, we look below at Rett Syndrome – a very rare neurological disorder believed to affect around 1 in 10,000 girls born worldwide every year. Caused by mutations on the X chromosome of the MECP2 gene, Rett Syndrome leads to severe brain impairments, with symptoms commonly including loss of speech, involuntary hand movements, reduced mobility, muscle weakness, and frequent seizures.

There have been just 30 trials in the US that have studied Rett Syndrome to date, meaning trial sites with experience of the disorder are severely limited. In the below chart, we map out the number of sites that have taken part in at least one previous study for Rett Syndrome by US state. 

Clinical research experience in the relevant field is an important consideration when selecting sites for a trial but, as shown in the example above, this could leave large parts of a country (e.g., the mid-west region of the US) completely underserved. This is just one example for one disease, but the picture will be similar for thousands of other indications in need of new therapies. The importance of mobile visit services, which are often designed to act as an extension of the study site, becomes obvious.

PCM Trials has previously supported a Phase III double-blinded study investigating a new therapy for Rett Syndrome. Mobile nurse teams worked closely with sites, a collaboration that helped to ensure excellent data quality and strong protocol compliance. As sites were shut down in response to the COVID-19 pandemic, PCM Trials stepped up its service with additional requests to handle blood draws and ECGs.

PCM’s nurses were essential in ensuring patient compliance with the protocol, providing caregiver training and support while simultaneously building rapport with participants and their families. There were numerous challenges faced by the team throughout the duration of this trial, from the pediatric population group itself to the pandemic restrictions and even a severe winter storm, but all data and samples were collected in a timely manner. To reduce the burden of participation, PCM Trials took care to work around school and caregiver schedules. This flexibility paid off, with more than 50% of the enrolled patients remaining in the four-year trial throughout its three stages.

To learn more about how PCM Trials’ mobile nurse visits contributed to the success of a rare disease trial, please download the case study below.