It’s not rare to have a rare disease

It’s not rare to have a rare disease

It’s not rare to have a rare disease 558 344 Exploristics

By Exploristics Chief Data Scientific Officer, Kimberley Hacquoil

It’s estimated that 300 million people worldwide are living with a rare disease and 85% – 90% of these are considered “serious or life threatening”. Even though there has been huge progress in advancing clinical innovations for rare diseases, 95% still don’t have a treatment option. This means that there is a significant unmet need for patients and demand for continued improvements in the way we approach drug development.

What is a Rare Disease?

The Orphan Drug Act defines a rare disease as a disease or condition that affects less than 200,000 people in the United States. The European Union defines a disease as rare when it affects less than 1 in 2,000 people. Other countries may have their own official definitions of a rare disease. Many rare diseases may only affect a few hundred or a few thousand patients worldwide.

There are about 7,000 known rare diseases, with more added each year. It is estimated that 80% of rare diseases are genetic in origin and approximately 75% impact children. Rare diseases are often complex from a biological standpoint. Usually there are a lot of unknowns regarding their biological mechanisms as well as  a lack of understanding of their natural histories.

Challenges to drug development

There are numerous challenges for drug development and approval of drugs, biologics and devices for treatment of rare diseases. These include:

  • Low prevalence and availability of patients which poses logistical challenges to conducting clinical trials.
  • Limited knowledge of the disease pathology and phenotypic heterogeneity which means there can be issues with identification and diagnosis of the patient population. This can hinder running clinical trials in this setting.
  • Rare diseases often impact children and are serious or life-threatening, which can add complications regarding safety risks and in many cases, it may be unethical to use placebo-controlled trials.
  • There is often a lack of well-defined or established and validated endpoints, outcome measures and biomarkers within rare diseases which can lead to regulatory hurdles.

Opportunities for innovation

Randomised controlled clinical trials are still considered the gold standard, however, traditional adequately powered studies may not be feasible. This leaves a large opportunity for innovation and novel approaches to the design, implementation, and analysis of trials.

When designing clinical trials, alternative design options should be identified, explored, and quantified to highlight the benefits and risks associated with different choices in a prospective manner. It’s likely that many designs could be possible, but understanding the applicability with respect to efficiency, risk of bias and practical implications is vital.

Engaging early with a range of stakeholders, including patients and statisticians, is important to ensure studies and development plans are well suited to the complex and unique circumstances each rare disease presents. Individuals with rare diseases desperately require new treatments to relieve their unmet clinical need. Currently, there are more than 1,000 medicines in development for rare diseases and conditions. By embracing more innovative study approaches to evaluate them during this process, we will be better-placed to  deliver them.


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