The Rare Disease Evidence Problem

More than 10,000 rare diseases affect over 30 million Americans and 400 million people worldwide, yet fewer than 10% have an approved treatment. That gap is both a clinical and evidence challenge, shaping decisions from clinical development through market access.

For rare disease therapeutics manufacturers, the standard evidence toolkit presents a fundamental mismatch. Claims databases depend on large populations for statistically meaningful results, but rare disease populations are small. A condition affecting 1 in 50,000 people may yield only a few hundred identifiable patients even in a comprehensive claims dataset—too few for robust subgroup analyses or a complete view of the patient journey.

Claims data also only captures what the healthcare system bills for, not what patients experience between appointments, the burden on caregivers, or why patients delay care.

Traditional value frameworks are not set up for rare diseases. Most health technology assessment (HTA) methodologies were designed for common diseases with large, homogeneous populations and established clinical endpoints. Applied to rare disease, they can undervalue therapies by focusing on measurable trial outcomes while missing what matters most to patients and families.

Closing that gap requires a different approach to evidence generation—one that starts with the patient and caregiver experience.

Why Qualitative and Survey-Based Research Is Uniquely Suited to Rare Disease

Qualitative and survey-based methods answer questions quantitative methods cannot. In-depth interviews with 20 to 30 patients can reveal disease impacts, care pathway barriers, and unmet needs that large datasets may miss. Surveys and interviews can also elicit psychosocial burden, caregiver impact, occupational disruption, quality of life, and the lived experience of navigating a poorly understood disease—domains often underweighted in traditional value frameworks.

Time is another factor: Where recruiting 100 patients with a rare disease for a quantitative study can take years, qualitative research offers a rigorous, efficient path to evidence.

Critically, surveys and interviews give patients a voice. Payers, regulators, and HTA bodies increasingly expect patient perspectives in evidence submissions. Qualitative and survey-based research can be the primary mechanism for capturing and translating that perspective into decision-relevant data.

How to Apply Qualitative and Quantitative Research Across the Rare Disease Lifecycle

1. Define Unmet Need Before the Market Defines It for You

Manufacturers that do not establish a clear, evidence-based definition of unmet need early risk allowing others to define it narrowly (e.g.,  around claims-visible utilization, direct costs, or available clinical endpoints. Qualitative interviews and surveys can establish which gaps in care patients, caregivers, and clinicians consider most consequential, including burdens not reflected in claims. Bringing those perspectives into the evidence strategy early gives manufacturers a defensible basis for clinical development, payer engagement, advocacy collaboration, and value communication. Companies should pair qualitative interviews with quantitative surveys to characterize the medical, indirect, nonmedical, and psychosocial burden of rare disease. Translating interview findings into survey measures can test how widely and severely those burdens are experienced and produce defensible estimates that complement claims-based evidence.

2. Surface the Impacts That Traditional Value Frameworks Miss

Rare disease therapies are often undervalued by HTA frameworks that were not designed to capture the full range of patient-relevant impacts. Financial and occupational burdens, caregiver disruption, social isolation, and psychological burden may be absent from cost-effectiveness models because the evidence to quantify them does not exist.

Survey research can fill these gaps by asking patients and caregivers to rank disease impacts and quantify associated financial costs. This can support patient-centered value narratives, payer negotiations, and regulatory discussions about what matters to patients.

It is important to use a structured process to identify, prioritize, and quantify patient-centered value elements for each study. Established approaches such as the Patient Perspective Value Framework (PPVF)— developed by Avalere Health and FasterCures with a multistakeholder steering committee—can help surface what patients and caregivers value most and translate those priorities into evidence useful to payers, HTA bodies, and cross-functional teams.

3. Inform Clinical Program Design and Endpoint Selection

Qualitative research can shape clinical development by identifying outcomes that matter most to patients, validating proposed endpoints, and surfacing concepts not captured by existing instruments.

It is critical to engage payers, clinicians, patients, and caregivers early enough for their insights to influence program design—not after endpoints and instruments are fixed. A disciplined approach includes stakeholder-specific discussion guides, comparative synthesis of decision-maker perspectives, and clear recommendations for endpoint selection, protocol design, and evidence planning.

4. Build the Evidence Foundation for Market Access

Qualitative and survey-based research plays a critical role in market access. Survey research can quantify economic burden, treatment gaps, care pathway barriers, and patient and caregiver experience. Qualitative research can explain why those gaps exist, what barriers limit access, and how a new therapy changes the experience of living with disease.

Together, these methods provide a richer evidence foundation than quantitative data alone—supporting formulary negotiations, patient support program design, and challenges to coverage policies.

Manufacturers should integrate qualitative and survey-based research with claims, clinical, and other quantitative analyses from the outset. Aligning these methods with payer and HTA expectations can ensure the evidence answers both scientific and market-access questions and gives cross-functional teams a shared foundation for launch.

Practical Guidance: Designing Qualitative and Survey-Based Research That Works

Not all qualitative and survey-based research is equally effective. In rare disease, where populations are small and resources are limited, design choices matter. The following principles can maximize the value of the investment.

• Start with the strategic question, not the methodology. Define the decision the evidence must support, the audience, what is already known, and the key gaps. Those answers should drive study design.
• Integrate qualitative and quantitative methods. Qualitative research identifies the domains that matter most; surveys quantify their prevalence and severity, while claims analyses provide healthcare utilization context. Together, they create a more complete picture of disease burden and unmet need.
• Partner with patient advocacy organizations to connect with patient communities, disease experts, and KOLs that can support recruitment, strengthen research instruments, and enhance credibility with patients and families.
• Validate instruments rigorously. In rare disease, disease-specific instruments may not exist, so surveys often need to be developed or adapted from disease-agnostic tools. Validation is essential to ensure they measure what they intend to measure.

The Cost of Waiting

Oftentimes, organizations defer qualitative and survey-based research until evidence gaps become urgent. By then, the opportunity to shape the evidence landscape may have passed.

The organizations that get the most from these methods treat them as strategic investments, not reactive measures. They generate evidence early enough to inform clinical development and build the foundation for a successful launch.

How Avalere Can Help

Avalere Health brings expertise in rare disease evidence strategy, qualitative and survey-based research design, and patient-centered outcomes to help clients generate evidence across the product lifecycle, from burden-of-disease characterization through launch readiness and post-market differentiation.

Our rare disease team combines structured interviews with patients, caregivers, clinicians, and payers; quantitative surveys; claims and other real-world analyses; and patient-centered value frameworks. We use these methods to characterize disease burden, identify patient and caregiver priorities, surface care pathway barriers, and translate qualitative insights into defensible estimates and recommendations aligned with payer and HTA requirements. For rare disease companies navigating small populations, limited data, and high stakes, qualitative and survey-based research is not a supplement to evidence strategy. It is the foundation.

To learn more about how Avalere Health can support your rare disease evidence strategy, connect with our team.