Managed Access Programs: Building the Evidence Infrastructure for Rare Disease

For many years, Managed Access Programs (MAPs) have served a single, vital purpose: providing patients with serious or life-threatening diseases access to promising therapies before they are commercially available or reimbursed. That compassionate mission remains unchanged.

What has changed is what the pharmaceutical industry now expects these programs to deliver. Increasingly, MAPs are being viewed not simply as a route to treatment, but as a strategic component of long-term planning. MAPs create an opportunity to generate the real-world evidence (RWE) needed to support reimbursement, demonstrate long-term value and reduce uncertainty surrounding rare disease therapies.

In many organisations, this represents a fundamental shift in thinking.

The evidence challenge in rare disease

The challenge is not a lack of innovation. The pipeline for orphan medicines continues to expand rapidly, driven by advances in gene therapies, cell therapies, precision medicines and RNA-based treatments.

The problem is that these innovations are often approved on relatively limited clinical evidence. Unlike therapies for more prevalent conditions, orphan medicines frequently reach the market based on:

• Small patient populations
• Single-arm clinical trials
• Surrogate endpoints
• Short follow-up periods
• Limited long-term safety data
• Uncertainty around treatment durability

These limitations reflect the realities of studying very small patient populations where conducting large, randomised clinical trials is often impossible. However, the uncertainty does not disappear once regulatory approval is achieved.

The questions regulators ask are no longer enough

Regulatory approval demonstrates that a medicine's benefits outweigh its risks. It does not necessarily answer the questions being asked by health technology assessment (HTA) agencies, reimbursement bodies and healthcare payers.

They increasingly want to know:

• Does the treatment continue to work five years later?
• Does it improve quality of life?
• Does it reduce hospital admissions?
• Does it delay disease progression in routine clinical practice?
• Does it justify the expected value/price over time?

For many orphan medicines, those answers simply do not exist at launch. As a result, post-approval evidence generation has become an essential part of the commercialisation strategy.

MAPs are uniquely positioned to support RWE generation

MAPs occupy a unique position within the product lifecycle - providing treatment during the period between regulatory approval and reimbursement, or before commercial availability in individual countries.

Historically, the focus during this period has been operational:

• Identifying eligible patients
• Managing approvals
• Coordinating supply
• Maintaining compliance
• Recording adverse events
  

Today, there is an opportunity to achieve considerably more. Every patient enrolled in a well-designed MAP represents an opportunity to generate structured, high-quality real-world evidence.

That evidence can include:

• Long-term safety
• Durability of response
• Patient-reported outcomes
• Quality of life
• Healthcare resource utilisation
• Treatment persistence
• Natural history comparisons
• Country-specific clinical experience

For therapies developed in very small patient populations, these data can become some of the most valuable evidence generated throughout the product lifecycle.

Momentum around RWE is building

Across Europe and internationally, regulators, HTA organisations and policymakers are placing increasing emphasis on real-world evidence to address the uncertainty that inevitably surrounds medicines for rare diseases:

• The European Medicines Agency's DARWIN EU initiative has expanded the routine use of real-world data (RWD) in regulatory decision-making.

• The European Parliament has highlighted the importance of patient registries, interoperable datasets and coordinated evidence generation as essential components of future rare disease policy.

• Health Technology Assessment International (HTAi) has recognised that evidence uncertainty is inherent to orphan medicines and that decision-making increasingly depends on integrating real-world evidence alongside clinical trial data. 

Industry studies have similarly shown that reimbursement submissions for orphan medicines increasingly incorporate real-world evidence to support pricing and access decisions.

The question is no longer whether real-world evidence should be collected, rather it is how to collect it effectively and without introducing additional administrative burden on both pharma and Healthcare Professionals (HCPs).

The operational opportunity

Unfortunately, many Managed Access Programs still rely on fragmented operational models.

Evidence collection is frequently managed through:

• Spreadsheets
• Separate electronic data capture systems
• Individual patient registries
• Multiple logistics providers
• Standalone safety databases
• Independent research platforms

This fragmentation creates familiar problems with inconsistent data, variable processes between countries and difficulty with full program oversight. HCPs in particular, find the process onerous with multiple sign-ons to multiple inconsistent systems. Evidence collection is treated as an additional project rather than an integrated component of program delivery. The aim should be to make evidence capture easier for healthcare professionals by embedding it into routine program workflows

Perhaps most importantly, valuable opportunities to generate meaningful evidence are often missed entirely.

Evidence-ready from the outset

Collecting high-quality evidence requires more than asking HCPs to complete additional forms. It requires deliberate program design with evidence objectives established before the first patient is enrolled.

Data collection should be proportionate, clinically meaningful and operationally sustainable with governance that ensures consistency across countries, vendors and participating centres.

Rather than evidence generation creating additional administrative burden, the operating system for the Managed Access Program should support this. Managed Access Programs should be evidence-ready by design.

A new role for Managed Access technology

This changing environment also changes what pharmaceutical companies should expect from technology. Historically, Managed Access platforms have focused on operational administration but the new generation of Managed Access Operating Systems need to support something broader.

They must provide the infrastructure to:

• Govern programs consistently across countries
• Coordinate multiple delivery partners
• Maintain regulatory compliance
• Capture structured operational and clinical data
• Enable longitudinal follow-up
• Support future evidence generation
• Provide portfolio-level visibility across global programs

Managed Access needs to become an enterprise capability that connects patient access, operational governance and evidence generation.

Looking ahead

Therapies for rare diseases will continue to push the boundaries of science - and uncertainty will remain an inevitable part of drug development. The organisations that succeed will not be those that get their medicines to patients quickest but those that are able to reduce uncertainty. That reality should not be seen only as a challenge. It is also an opportunity to design better evidence strategies from the outset