HTA for Rare Diseases: Policy Development

HTA for rare diseases faces unique challenges:

• Small patient populations limit clinical evidence
• High treatment costs strain budgets
• Ethical issues in assessing value
• Traditional cost-effectiveness analyses don't fit

Key policy elements:

• Flexible evidence requirements
• Alternative economic models
• Patient and clinician input
• Ethical frameworks

Country approaches:

Country	Approach
France	Early Access Program
Scotland	Ultra-Orphan Medicines Pathway
Australia	Life Saving Drugs Program

Implementation needs:

1. Clear goals and standards
2. Flexible review methods
3. Uncertainty management
4. Stakeholder engagement

Future focus: AI diagnostics, personalized therapies, global collaboration.

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Current State of Rare Disease HTA

HTA for rare diseases faces challenges due to:

• Tiny patient populations
• Limited clinical data
• Sky-high treatment costs
• Ethical dilemmas

A Canadian study of 63 rare disease drug submissions showed an average of just 190 patients per study. Annual treatment costs averaged C$215,631.

Countries are taking different approaches:

Country	Approach
France	"Temporary Authorization for Use" (ATU)
USA	Orphan Drug Act
Scotland	Ultra-orphan medicines pathway
England	NICE's Highly Specialised Technology Programme
Sweden	TLV's flexible approach for unmet needs

Key players include government agencies, patient groups, pharma companies, healthcare providers, and health economists.

Annie Kennedy of EveryLife Foundation notes:

"We often see HTA policies that don't reflect input from clinical experts or patients with rare disease experience."

This highlights the need for more patient and expert involvement in rare disease HTA.

Key Parts of HTA Policy for Rare Diseases

Evidence requirements:

• Accept smaller studies (average 190 patients in Canadian review)
• Consider surrogate endpoints
• Use real-world data (like France's ATU program)

Cost analysis challenges:

Issue	Solution
High costs	Consider broader impact
Few comparators	Use flexible models
Uncertain long-term outcomes	Managed entry agreements

Patient and clinician input is crucial. The UK and Germany have advanced processes for this.

Ethical issues to address:

• Balancing access and spending
• Valuing health gains for severe illnesses
• Considering societal impact (nearly $1 trillion in 2019)

Creating a Full HTA Policy Plan

Set clear goals:

• Define "appropriate access"
• Improve stakeholder coordination
• Manage uncertainty while improving access

Create tailored assessment criteria:

Criteria	Approach
Evidence	Accept smaller studies, surrogate endpoints
Economic evaluation	Use flexible models, consider wider impact
Patient input	Include patient experience data

Use flexible methods:

• Fast-track innovative drugs
• Implement Managed Access Plans
• Try Multi-criteria Decision Analysis

Handle uncertainty:

• Build rare disease data infrastructure
• Use patient registries for long-term data
• Accept lower p-value thresholds

Darius N. Lakdawalla notes:

"HTA bodies often ignore or make exceptions to cost-effectiveness analyses for rare diseases. This shows they don't capture the full value."

Good Examples in Rare Disease HTA Policy

Lessons from other countries:

Country	Policy	Key Features
France	Early Access Program	Fast-track innovative drugs
Scotland	Ultra-Orphan Medicines Pathway	3-year evidence period
Australia	Life Saving Drugs Program	Covers effective but costly drugs

France, Germany, and the Netherlands allow market access at set prices if yearly budgets stay under €30M, €50M, and €2.5M.

Key takeaways:

• Flexible evidence rules (FDA approved Galsulfase with just 7 patients in a key trial)
• Patient involvement is crucial
• Traditional cost-effectiveness often fails for rare diseases

New ideas:

1. GRACE method: Accounts for illness severity
2. Consortium models: Academia-industry-patient partnerships
3. Patient registries: Gather long-term data
4. Regulatory changes: U.S. STAT Act aims to improve FDA rare disease approach

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Putting HTA Policies into Action

Implementation steps:

1. Set clear access goals
2. Create flexible review methods
3. Set budget thresholds
4. Engage stakeholders early

Preparation needs:

Resource	Purpose
Specialized HTA teams	Train in rare disease complexities
Patient registries	Collect long-term outcome data
Funding mechanisms	Set up special programs
Communication platforms	Enable stakeholder input

Monitor results:

• Track approval rates
• Measure access times
• Gather stakeholder feedback
• Assess budget impact

Regular reviews with patient groups and experts are crucial to keep policies aligned with real needs.

Solving Policy Creation Problems

Data scarcity solutions:

• Use patient registries and real-world evidence
• Allow evidence generation periods
• Lower statistical thresholds

Budget management:

Strategy	Example
Budget thresholds	France (€30M), Germany (€50M), Netherlands (€2.5M)
Managed entry agreements	Used for treatments like nusinersen
Special funding programs	Australia's Life Saving Drugs Program

Balancing stakeholder needs:

• Early engagement
• Multi-dimensional value assessment
• Ethical frameworks (like INESSS in Canada)

Regular stakeholder reviews help keep policies on track.

What's Next for Rare Disease HTA Policy

Emerging tech:

• AI diagnostics (Mayo Clinic identified causes for 30% of patients in 2023)
• Personalized treatments (like Dr. Cousin's antisense oligonucleotide trial)
• Advanced analytics for complex data

Global teamwork:

Initiative	Purpose	Impact
Global Network for Rare Disease	Build expertise network	250+ clinicians and advocates
E-Rare	Connect national funders	26 bodies across 18 countries
IRDiRC	Global research cooperation	Aims for 200 new therapies

Research priorities:

1. New value assessment methods
2. Patient-driven research
3. Global access strategies
4. Long-term outcome tracking

Dr. Margot Cousin says: "It's a really exciting time for rare disease therapeutics."

Conclusion

Key points:

• Standard HTA methods often fail for rare diseases
• Teamwork is crucial for effective frameworks
• Patient input and real-world data are vital
• Flexible approaches improve orphan drug access

Collaboration needs:

Stakeholder	Role
Policymakers	Create special pathways and higher thresholds
Pharma	Plan early for reimbursement
Patient groups	Provide experience data and drive research
HTA bodies	Use pre-authorization for some orphan drugs
Researchers	Share data globally

Next steps:

1. Global data sharing
2. Patient-centered approach
3. Innovative funding models
4. Ongoing policy updates

Extra Information

Key terms:

Term	Definition
HTA	Evaluates health tech impacts
Rare Disease	Affects < 5 in 10,000 people
Orphan Drug	Treats rare conditions
Ultra-Rare Disease	Affects < 1 in 100,000
Early Scientific Advice	Pre-approval evidence planning
Managed Access Plan	Controlled access with data collection

Further reading:

• "Health Technology Assessments and Rare Diseases - Volume 13(3,4)"
• National strategies from Australia and Canada
• HTA body websites (NICE, G-BA)
• EURORDIS patient perspectives
• Industry reports on orphan drug challenges

A Canadian review found median annual costs of CAN$330,395 per patient for ultra-rare disease drugs.

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