Developing drugs for rare diseases involves complexities beyond those typically seen in large trials for more common conditions.

Challenge # 1: Enrolling, engaging and retaining patients

Finding enough patients who fit inclusion and exclusion criteria for a particular trial can be difficult, because by definition, rare diseases affect very few people. Also, rare disease patient populations are often widely dispersed and heterogeneous in disease subtype, symptoms, stages and exposure to prior treatment. 

A solution to this challenge is to use real-time patient data and physicians’ notes from electronic health records (EHRs) to model various recruitment scenarios, by partnering with a CRO that already partners with organisations that collect EHRs.

Challenge # 2: Designing and evaluating clinical trials

Designing a trial that can meet enrollment goals and designating an appropriate comparator make it difficult for rare disease drug developers to gather sufficient data and build a compelling value story for their product. 

Trials must be simplified, flexible and attractive to enroll enough patients. It is critical that clinicians, statisticians, and other well-qualified professionals collaborate to build a study design that is attractive to patients and develop a strong evidence-generation plan.

Challenge # 3: Ensuring the quality of patient data

Measuring clinical trial outcomes in rare disease patients is especially challenging because they often exhibit huge diversity in their clinical presentation and histories. Variables including age, disease progression, and disease severity influence reported outcomes, whether they are clinician-reported, observer-reported, or patient-reported outcomes (PROs).

Sponsors can benefit from engaging clinical outcome assessment (COA) experts who understand the nuances of disease progression and PROs in rare diseases, who will provide tools and knowledge needed to support collection of valid data, and help find the most appropriate and valid PROs to include in their orphan drug development.

Challenge # 4: Global regulatory requirements and payer evidence

Since rare disease research seldom fits the traditional randomised clinical trial mould, collecting and communicating evidence that is compelling to regulators and convincing to payers is challenging. Also, the definition and regulations of rare and orphan diseases differ considerably by location. 

A solution is to generate real-world data (RWD) that fulfils regional and worldwide regulatory and payer requirements using a patient-centric approach through the use of wearables, apps and EHRs. 

ICON has the experience and expertise you need to bring your rare disease drugs to market.  For further information, please contact one of our experts

This blog is an edited version of “Overcoming Four Challenges to Successful Rare Disease Drug Development” which appeared in the April 2017 edition of Pharmafocus. To view the full article, please visit

Rare and orphan diseases insights

ICON's Rare and Orphan Diseases team provides analysis including whitepapers, blogs and contributions to media and industry conversations relating to all aspects of rare and orphan diseases in clinical trials.

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