Sunday is Rare Disease Day! The last day of every February is dedicated to raising awareness among the general public and decision-makers about rare diseases, and their impact on patients’ lives. This is a cause near and dear to our hearts here at Broadstreet. Rare disease research accounts for a significant amount of the work we do; over 150 of our projects in the past 5 years have centered around rare diseases. Because of that, today we thought we’d focus on some of the unique challenges and new frontiers found in rare disease research. The term rare disease can be confusing because people often have the perception that if they have heard of a condition, it can’t be rare. But, worldwide around 400,000,000 people suffer from a rare diseases, and these conditions touch the lives of people all around us. While the definition of rare disease varies from country to country, generally a condition is considered rare if it affects fewer than 1 in 2,000 people. Examples of relatively frequent and well-known rare diseases include hemophilia and Hodgkin lymphoma.

Over 7,000 rare diseases have been identified

To date, over 7,000 rare diseases have been identified. Approximately 80% of those have a genetic basis and more than 50% of patients with rare diseases are children. Having a rare disease can be isolating for patients and their families; often patients don’t know anyone else in their community with the same condition. Information about the disease can be very limited and there may be no treatment. In addition, getting a diagnosis can be a long and frustrating process, which can be detrimental in cases where early treatment can bring benefits to the patient.

Researching rare diseases poses considerable challenges

Part of the reason diagnosis and treatment of rare diseases are so complex is because these conditions present a number of unique challenges for research. Because of the lack of information about disease progression, researchers and clinicians don’t have a very good understanding of how the condition can be expected to affect a patient during different points of their life. Additionally, rare diseases pose complex issues around how research studies are conducted both in terms of methodology, ethics, and even funding. Briefly, those issues include:

• How to conduct rigorous studies when, because of disease rarity, it is difficult to recruit enough similar participants to meet accepted sample size criteria (eg. groups of the same age, point in disease progression, genotype, etc.).
• How to compare results across studies when there is often a lack of standardized measures tailored to the symptoms of that particular rare disease. This lack of comparability can make it difficult to understand the relative efficacy and safety of one treatment verses another.
• Is it ethical to conduct trials with untreated control populations thus denying some patients a potentially life-saving treatment? This is particularly a concern for progressive conditions where early treatment may result in the most benefit.
• How do we fund research in rare diseases in light of economic challenges such as limited drug budgets and the difficulty in recouping the high costs of research and development from a small pool of eligible patients.

New frontiers in research offer hope

Despite these challenges, a number of exciting new frontiers are emerging in rare disease research. Firstly, the perception that research into rare diseases only benefits a small group is beginning to change as wider applications for rare disease research emerge. For example, recent research on treatment for the rare disease Hutchinson-Gilford progeria syndrome, which affects the vascular system, is providing insight into potential treatments for cardiovascular disease, one of the world’s most common and deadliest medical conditions. And there are other reasons to feel positive about the future of rare disease research. Governments are increasingly putting focus on finding treatments for rare disease with the Orphan Drug Act in the US and the European Orphan Medicinal Products Regulation for example both facilitating more research on these types of conditions. In addition, with so many rare diseases being genetic in origin, recent advances in genetic research are also a source of hope. The emergence of gene therapy and personalized medicine has allowed for the development of treatments targeted to correct specific genetic issues like missing or defective genes. The result of all of this is that in recent years the US government has approved over 500 treatments for rare diseases.

Broadstreet is very positive about the future of rare disease research

On our rare diseases projects, we tend to work with small teams at small companies. Because of that, we have been lucky enough to get involved at all stages of treatment development, from working with the early clinical team; informing clinical trial design; developing and implementing evidence generation plans; and ultimately, helping spearhead the evidence communication platforms. This has given us a profound understanding of rare disease research but beyond that a deep empathy for the people affected. HEOR so often involves big data and big statistics, so the small numbers of patients involved in rare disease studies really brings home to us the people whose lives are so gravely affected by these conditions. Being able to make a contribution to potentially improving their lives gives meaning every day to the work that we do.