The Power of Patient-Centricity in Rare Disease Studies

Orphan drug discoveries promise unprecedented opportunities, as well as challenges. Unfortunately, research in the rare disease space presents some of the highest hurdles in medicine due to the nature of their small, complex patient populations.

Therefore, clinical trial design and implementation require a level of operational orchestration, scientific expertise, regulatory knowledge, and patient-centric workflows that many sponsors find cumbersome. 

This level of complexity heavily impacts patient recruitment and retention for eligible rare disease populations. Orphan drug studies suffer the same industry-wide challenges with sourcing, screening, and retaining the right patients for their trials. But issues are amplified in rare disease populations for several reasons:

  • Small populations of eligible patients are distributed over broad geographic regions
  • A large percentage of the rare disease population are pediatric patients 
  • Many patients live with debilitating and life-threatening conditions 
  • There are few centers for diagnosis1
  • Few researchers have experience conducting studies with rare disease patients 
  • Rare diseases often lack validated outcome measures 
  • Treatments options are often costly 

To conduct a successful orphan drug study, trials must be designed with patient-centricity in mind.

These fragile patient populations require an innate understanding of their clinical disease and how they and their caregivers experience it in their daily lives.

Therefore, researchers must design their trials in a way that takes their unique populations into account to enhance the trial experience, reduce patient burden, and achieve more meaningful outcomes for these critically important trials. 

Current State of Rare Disease Patient Engagement 

To date, little research exists that shows the impact of patient engagement on rare disease patients. The reasons for this are due to the inherent challenges faced by these patient cohorts: 

  • It can take patients years—and multiple specialists—before receiving the correct rare disease diagnosis. 
  • Once diagnosed, few rare diseases have effective treatment options available. 
  • Without effective treatment, many progressive or life-threatening rare diseases can result in loss of abilities or premature death. 
  • A combination of small cohorts coupled with clinical heterogeneity and complex disease dynamics make patient engagement challenging.  
  • There is a diametric difference between the vast number of rare diseases and small numbers of rare disease patients. 

These challenges are only expected to increase. Every year, 250 – 280 new rare diseases are identified due to an increase in new subtypes, diagnostic improvements, and a better understanding of disease pathology.2

These new discoveries add to the 6,000 – 8,000 known rare diseases that impact 3.5 – 5.9% of the global population.2 

Additionally, regulatory guidance like the United States Orphan Drug Act or European Union Regulation on Orphan Medicines reward innovation for unmet patient needs.

This has driven an increase in orphan drug interest, with experts predicting orphan drugs will account for one-fifth of all prescription drug sales by 2024.2

With the rise in research paired with increasingly dispersed patient populations, it’s critical for rare disease trials to formulate concrete patient engagement strategies. 

The Power of PAOs and Patient Input

With roughly 7,000 known rare diseases, it’s impossible for sponsors or CROs to be experts in all of them. Patient Advocate Organizations (PAO) are a powerful bridge between clinical teams and their patient cohorts. Collaboration with PAOs at the onset of a study is critical to understanding the unique patient journey of a particular disease and identifying meaningful endpoints.

With direct access to patient groups, PAOs can help promote upcoming trials, answer questions about trial participation, and weigh in on protocol design. In fact, a study found that PAOs contribute to over 40% of patient enrollments in rare disease trials.3 

PAOs not only act on behalf of their patient groups, but they can also enlist patients to weigh in on study design. Patients living with these rare conditions can provide keen insight that enhances enrollment, retention, and engagement in your trials.

This buy-in is crucial during protocol design to ensure the trials are conducted in a way that enhances patients’ experiences while reducing trial burden and protocol complexity. 

Orphan drug studies are also fraught with uncertainties that arise from a lack of information around:

  1. Value for sponsors 
  2. Clinical benefit
  3. Market approval 
  4. Potential patient adoption 
  5. Affordability 

Patient and PAO input on orphan drug protocol design can identify potential barriers to enrollment and retention, including:

  • Providing a better understanding of the disease burden and level of unmet needs.
  • Modifying protocol so that patients living with rare conditions find value in the study.
  • Developing outreach messaging and materials specific to unique patient cohorts. 
  • Establishing more responsive services that result in better outcomes for studies with limited historical validation. 
  • Identifying barriers of entry and developing logistical support. 
  • Enriching engagement and retention strategies with patient-centric workflows. 
  • Identifying outcomes and costs often missing from assessments of new therapies.

More than other therapeutic areas, involving PAOs and patients as partners in orphan drug studies is critical. In fact, 82% of rare disease studies report that patient- and PAO-reviewed protocols provide substantive input on study design and impacted patient engagement.2 

The Next Phase of Orphan Study Engagement

The pathway to patient engagement in orphan drug studies is still unpaved. No two rare disease trials are the same, which is why a coordinated effort from all stakeholders is needed. 

Clinical teams need to find ways to determine: 

  • What is the disease burden and level of unmet needs for this specific disease? 
  • What is the intended treatment impact of the potential drug? 
  • What is the patient’s perception of change? 
  • What is the meaningfulness of the perceived change? 

Understanding these outcomes is key to recognizing the nuances and challenges of orphan study patients and caregivers. It also allows clinical teams to design trials that reflect the knowledge of what unique patient cohorts and their families are experiencing.

Protocols can be structured based on visit frequency, the need for any specialized testing, and highly diverse clinical diseases.

By investing in patient engagement early in your orphan drug studies, sponsors can reduce timelines, costs, and lower their development risk why better supporting the patient populations who need it most. 

With the rise of rare disease research, these efforts are needed now more than ever. Medrio has supported over 25+ therapeutic areas and understands the flexibility needed to achieve rare disease patient engagement.

Our unique suite of solutions is designed to enable patients to interact with clinical studies remotely throughout the process, from consenting to post-approval. 

Are you ready for the next phase of orphan drug research? Sign up for a demo to learn more.


1 Patient Engagement in Clinical Trial Protocol Design and Recruitment Strategies: What Does It Mean for Orphan Drug Manufacturers?

2 Lanar, S., Acquadro, C., Seaton, J. et al. To what degree are orphan drugs patient-centered? A review of the current state of clinical research in rare diseases. Orphanet J Rare Dis 15, 134 (2020).

3 How Engaging Patients in Trial Design Maximises Orphan Drug Success

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