By John Seaner
Rare Disease, Rare Opportunity: How A PXO Unlocks Enrollment and Equity in Ultra-Orphan Trials
Rare disease trials are often characterized by a single assumption: smaller patient populations mean simpler studies. Fewer patients, fewer sites, faster timelines, right?
Wrong.
In truth, rare disease trials are among the most complex and fragile studies in the clinical development pipeline. These trials face challenges in:
- Patient identification.
- Diagnosis delays.
- Eligibility barriers.
- Trust gaps.
- Care coordination.
- Long-term retention.
And the most dangerous assumption of all? That rare disease patients are eager to participate simply because they have limited options.
This underestimates the emotional, logistical, and psychological weight of participating in research for a condition that has historically been ignored, misdiagnosed, or misunderstood.
As a Patient Experience Organization (PXO), Jumo Health understands these challenges. And our PX model provides an answer: a structured, behaviorally intelligent system for engaging rare disease patients and caregivers with empathy, clarity, and trust.
In this post, we explore how this PX model transforms rare disease trials from high-risk recruitment efforts into inclusive, scalable, and ethically sound enrollment ecosystems.
The Rare Disease Recruitment Crisis
There are over 7,000 rare diseases, yet less than 10% have FDA-approved treatments. Many rare conditions are ultra-orphan, affecting fewer than 1,000 patients worldwide.
Despite this urgency, the numbers paint a bleak picture:
-
- Average diagnosis delay: 5–8 years
- Screen failure rates: Up to 60% due to narrow eligibility or comorbidity exclusions
- Trial awareness: Rare disease patients are 3x less likely to hear about trials than those with common conditions
- Retention drop-off: As high as 45%, especially in trials with intensive protocols or long durations
Traditional recruitment strategies fall short. Why?
Because for rare disease patients, participation isn’t just a clinical decision, it’s a deeply personal, often traumatic milestone. Many patients are being asked to trust an industry that’s ignored them for decades.
Our PX model is built to repair that trust and convert it into sustained participation.
Rare disease patients don’t arrive at trial participation casually. Their journey is long, nonlinear, and emotionally turbulent.
The Rare Disease Decision Journey: More Than Just a “Yes”
Key phases include:
Symptom Suspicion:
Years of misdiagnosis, false hope, and frustration
Diagnosis Event:
Relief, grief, and identity shift
Search for Options:
Peer forums, advocacy groups, and medical tourism
Encountering Research:
Skepticism, confusion, and guarded optimism
Decision-Making:
Navigating unclear benefits, potential risks, and family concerns
This journey often includes caregiver triangulation, insurance fights, and medical gaslighting. By the time a patient hears about a trial, they are emotionally and cognitively spent.
The PX model honors that reality by designing support systems for the entire decision journey not just the enrollment moment.
PXO in Action: A Custom Framework for Rare Disease Trials
We deliver activation for rare disease trials through 5 integrated layers:
1. Trust Architecture
2. High-Context Clarity
3. Caregiver Integration
4. Decentralized Support Infrastructure
5. Continuity-Driven Retention Systems
Let’s explore each.
1. Trust Architecture
Rare disease patients often enter the trial conversation with a trauma-informed mindset. They’ve been dismissed, misdiagnosed, and underserved.
A PXO builds trust using:
Lived Experience Storytelling: Patient and caregiver narratives integrated into trial education materials
Transparent Framing: Clear articulation of knowns, unknowns, and the purpose of the study
Motivational Congruence Mapping: Aligning trial goals with what patients value (e.g., slowing decline, being heard, helping others)
Co-Created Content: Resources developed with rare disease advocates, not just medical writers
In one neuromuscular disorder trial, PXO-based trust tools increased enrollment intent by 47% among families previously disengaged from research.
2. High-Context Clarity
In rare disease trials, clarity isn’t just about simplifying language, it’s about contextualizing every detail for a patient population with unique lived realities.
A PXO addresses this with:
Disease-Specific Visual Consent Guides: Tailored to illustrate how the trial may impact progression, daily life, and caregiver support
Treatment History Mapping Tools: Helping patients visualize how trial participation integrates with current regimens, devices, or assistive technologies
Benefit-Risk Positioning Grids: Presenting what’s known about the investigational therapy in the context of current standard of care (or lack thereof)
Decision Dialog Templates: Scripts and tools for family conversations, especially in conditions affecting minors or cognitively impaired adults
The result? Patients and caregivers feel prepared, not pressured, leading to higher-quality consent and fewer early withdrawals.
3. Caregiver Integration
Most rare disease trials involve proxy decision-makers such as parents, spouses, or legal guardians. Yet many trial designs treat caregivers as bystanders.
A PXO repositions them as co-pilots, with:
Parallel Education Tracks: Separate but aligned materials for patients and caregivers
Caregiver Burden Planners: Tools to visualize time, travel, emotional, and financial impact over trial duration
Emotional Resilience Guides: Supporting caregivers in managing hope, guilt, fear, and grief throughout the study
Logistics Coordination Modules: Simplifying transportation, visit scheduling, and communication with schools or workplaces
This isn’t just ethical, it’s operational. Trials that engage caregivers retain patients longer and experience fewer protocol deviations.
4. Decentralized Support Infrastructure
Rare disease patients often travel hundreds of miles to access care. Many live in rural or medically underserved areas.
A PXO builds distributed access pathways with:
Tele-Consent and Tele-Coordination: Enabling participation without geographic restriction
Home Health Visit Toolkits: Visual and procedural materials for mobile nurses and phlebotomists
Digital Visit Prep Engines: Interactive modules that simulate visits, so patients know what to expect even if the site is far away
Remote-Ready ePRO Systems: Designed for ease of use across age, tech literacy, and cognitive function
This decentralized approach expands access while reducing dropouts driven by travel fatigue and logistical overwhelm.
5. Continuity-Driven Retention Systems
Rare disease patients are often in trials for months, even years. Many studies include open-label extensions or post-market observational arms.
A PXO delivers long-term retention through:
Visit Milestone Recognition: Behavioral nudges that reinforce progress and contribution
Personalized Information Refreshers: Updates that re-explain trial goals, procedures, and importance as context shifts
Care Continuity Coordination: Supporting transitions between trial care and routine clinical care
End-of-Trial Transitions: Preparing patients and families emotionally and medically for what comes after the study
In a pediatric lysosomal storage disorder trial, PX interventions led to a 66% improvement in end-of-trial visit attendance compared to sponsor benchmarks.
Metrics That Matter
A PXO tracks rare disease trial performance using:
- Patient Decision Readiness Score (PDRS): Measures emotional, informational, and logistical readiness pre-consent
- Caregiver Confidence Index (CCI): Assesses caregiver understanding and support capacity
- Equity Access Score (EAS): Monitors trial reach across geographic, socioeconomic, and racial demographics
- Behavioral Retention Probability (BRP): Predicts dropout risk based on real-time engagement signals
These metrics allow clinical operations teams to intervene early and optimize continuously.
Why Clinical Operations Must Lead the Shift
Rare disease trials can’t afford waste. Every patient counts. Every visit matters. Every dropout jeopardizes the study.
PX optimization is not a “nice-to-have.” It’s a mission-critical system that delivers:
Faster enrollment
Higher consent quality
Lower screen fail rate
Longer retention
Greater data equity
Higher regulatory confidence
Conclusion: Respect Builds Results
Rare disease patients are not desperate, they’re discerning. They’ve waited years for this moment. And when they agree to participate, they’re not just volunteering, they’re advocating.
A PXO ensures that this act of advocacy is met with respect, clarity, and support at every touchpoint. If your next rare disease trial can’t afford enrollment delays, protocol amendments, or mid-study attrition, let’s talk.
