There are more than 7,000 rare diseases, and they affect approximately 4% of the total world population.1,2 These include genetic and environmental diseases as well as infectious illnesses and rare cancers. Although some rare diseases tend to be less rare in certain regions or within specific demographics, all rare diseases pose sizable challenges to patients and those dedicated to providing quality care and breakthrough treatments to address the multitude of unmet needs.
Decentralized clinical trials (DCTs) and the patient-centric options they provide are proving to be a valuable solution to some of the unique challenges presented by rare disease research. In the face of readjustments caused by COVID-19, decentralized strategies allow patients, family members, caregivers, medical practitioners, and sponsors to conduct trials that are flexible and tailored to best suit a patient’s situation. More than ever before, these strategies are enabling patients and care teams to overcome some of the burdens associated with rare disease trial participation.
Despite a myriad of challenges as the patient and caregivers navigate the pathway to obtain a diagnosis, patients and their loved ones relentlessly pursue a correct diagnosis and then research treatment opportunities. This process is often complicated, arduous, expensive, painful, and discouraging. For many patients, obtaining a rare disease diagnosis answers a lot of questions, while also bringing up new ones, spurring the search for understanding and knowledge about the disease and treatment.
During that search, patients and their loved ones are fortunate if they are able to find resources and networks that not only share information and experiences, but also give additional support and a sense of camaraderie. These groups form close-knit patient advocacy communities and are involved in keeping each other up-to-date on the latest news related to the rare disease. They also promote the community’s interests with regulators, legislators, drug developers, and other key influencers. Social media platforms and virtual video technology have increased the ease of staying in touch globally and diffusing pertinent information.
Upcoming trials are a frequent topic of discussion. The openness in these communities allows patients and their families to discuss their feelings about advances in research and clinical studies which may be of interest. Patients and parents, consider the experiences of other individuals participating in trials, including the phase of the research, previous research in humans, potential risks, and potential clinical benefits. Thanks to these communities and networks, there is greater access to trusted sources who are willing to share their thoughts and opinions regarding the research opportunities – and if there are more suitable studies and treatment options available.
Benefits of participating in clinical trials
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Challenges in participating in clinical trials
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Patients, families, and caregivers weigh a variety of other factors when contemplating the benefits and drawbacks of participating in a trial. These factors often relate to the burdens and barriers of participation, and how enrolling affects current and long-term daily life.
Rare diseases can display a wide spectrum of phenotypes, for example, from severe to attenuated, and therefore affect a patient’s neurological, behavioral, and skeletal systems, among others. Symptoms can vary tremendously among patients even with the same rare disease diagnosis, and severe symptoms directly correlate to how greatly a disease impacts the patient’s life. Some of these symptoms may cause it to be extremely difficult for patients to participate in less flexible trials; for example, traveling to a clinical site may require specialized planning for caregivers and transportation equipment like dedicated nurses and oxygen tanks to attend a study visit.
Sponsors and others in the clinical trial space need to understand these decision factors and burdens as thoroughly as possible in order to take them into account when planning and executing a successful study.
DCTs offer the option to minimize the restraints of location or travel logistics when considering trial participation. Patients may be able to avoid or reduce the often long distance travel to clinic sites, which can be viewed as burdensome and disruptive or even unacceptable. This is crucial because clinical sites are often centrally located typically in larger metropolitan areas, whereas patients with rare diseases are spread around the world and often in remote and rural, and even ultra-rural, areas. Technological advances harnessed by a DCT strategy can supplement and virtually replace traditional techniques utilized in studies, making the trials highly flexible and accessible to patients globally, even from the comfort of their own homes.
In addition to a patient’s own care, travel arrangements may be complicated if there are other family members, especially children (or even aging parents), who require their care. This may necessitate arranging additional care options, such as childcare; if it is the caregiver’s professional full-time job, they may also be required to organize alternative caregivers to take their own place for that time.
Another considerable burden is that family caregivers may require time off from their own jobs, resulting in potential salary reductions or using precious paid time off. Even if the travel costs are later reimbursed, sometimes patients and families may not have the resources to cover the costs in advance, making participation an even greater challenge.
Providing monetary support to cover daily expenses while traveling to the site for a study visit, organizing travel arrangements and accommodations, and helping solve for gaps in the care of dependents are crucial to lessen the burden on patients and loved ones, encouraging their participation in rare disease trials, increasing enrollment figures, and improving retention rates.
Challenges related to location, availability, and reimbursement directly correlate to how feasible it is for a patient to participate in a study. Traditionally, study designs induce limits and inadvertently cause a significant percentage of key patients to be excluded from the trial pool due to their inability to participate simply because of the trial design.
Although it can be challenging for sponsors to plan a trial taking the ranges of symptoms and factors into account, designing an inclusive trial increases the patient recruitment rate, which is often lower than desirable. Having a larger and more diverse enrollment ensures that the study population is not inadvertently skewed towards one segment such as mildly-symptomatic patients – a crucial factor in the success of clinical studies and their reliability for treatment development.
Decentralized trial designs enable improved consideration of patient needs (providing flexibility for patient symptoms, locations, caregivers, and financial worries), affording another important advantage. The protocols are more agile and can be tailored to satisfy a patient’s circumstances to a more customized degree.
For example, many patients are likely to have a dedicated healthcare team, and even a standard of care (SOC) provider with whom they have been working closely, often having a history that goes back many years. If they can remain with their familiar physician as part of the trial design, trust in the process and long-term retention are enhanced throughout the inevitable ups and downs of trial participation.
Decentralized trials and a growing orientation to patient centricity, afford all participants better reasons and easier access to join rare disease trials. DCT designs help overcome challenges related to geography, travel, accommodations, specialized individual patient arrangements, symptom management, expenses, and changing care providers. When these challenges are recognized and addressed to the greatest degree possible, more patients with rare diseases are able to participate in trials and generate more diverse and accurate patient population representation. In return, more sample diversity will provide more conclusive study results, leading to better treatment protocols for all current and future patients of rare diseases.
Click here to learn about Precision’s approach to decentralized clinical trials >
Esther Mahillo is the Vice President of Operational Strategy and Feasibility at Precision For Medicine. Dr. Mahillo earned a PhD in Biochemistry at Autonoma University of Madrid and has 25+ years of experience in the clinical research arena, (22 of them in global oncology trials). Dr. Mahillo is a master’s program professor at 3 different universities and authored 3 books, 21 scientific articles, and 24 contributions to scientific congresses. In 2015, Dr. Mahillo was awarded the first prize of the Spanish Society of Medical Oncology (SEOM) contest for her work on promotion of clinical research.
1. Sburlan EA, Voinea LM, Alexandrescu C, et al. Rare ophthalmology diseases. Rom J Ophthalmol. 2019;63(1):10-14.
2. Wakap SN, Lambert DM, Alry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database [published online September 16, 2019]. Eur J Hum Genet. doi: 10.1038/s41431-019-0508-0.
Precision for Medicine is part of the Precision Medicine Group, an integrated team of experts that extends Precision for Medicine’s therapeutic development capabilities beyond approval and into launch strategies, marketing communication, and payer insights. As one company, the Precision Medicine Group helps pharmaceutical and life-sciences clients conquer product development and commercialization challenges in a rapidly evolving environment.
