Data Detectives: Overcoming the Challenges of a Rare Disease Evidence Base to Develop a Compelling Value Narrative

Although our five top tips for a winning value dossier are critical regardless of the product or disease, rare diseases present a unique set of additional challenges when it comes to developing a comprehensive and compelling value dossier.

Lets set the scene. You are 18 months away from launching a groundbreaking therapy – the first ever specifically licensed for this ultra-rare condition. This treatment promises to bring a significant and transformative change to the lives of those affected. However, the condition itself was only identified 15 years ago, resulting in a sparse and fragmented data landscape. Your pivotal trial, crucial for reimbursement, is a non-randomised controlled trial (RCT) involving under 50 patients.

You have been tasked with turning this challenging evidence base into a compelling case for the value of your product. So, where should you start?

Step 1:
Collecting and Interrogating the Evidence

Think outside the box with literature reviews

Systematic literature reviews (SLRs) frequently inform value dossiers, but standard SLR methodologies may not generate the evidence you need in rare diseases. Ensure your reviews capture observational studies and consider targeted reviews of case studies for patient-level data where minimal published evidence is available. Broaden your search to proxy conditions if there is limited economic evidence in your target condition.

Utilise data inventories and understand the evidence gaps

A data inventory categorising sources by topic area can be extremely useful in identifying high-level gaps within a limited or weak evidence base, and can also help with prioritising data sources to summarise within the value dossier. If also categorised by geography, a data inventory may help identify local evidence gaps such as regional epidemiology estimates, which are a common evidence gap in rare conditions but are of importance to payers.

Scrutinise your understanding of the natural history of the disease

A deep understanding of the natural history of the relevant disease is crucial for demonstrating how your treatment can make a difference. However, it is common to have limited published literature on natural history of rare diseases. You should identify your strongest and most compelling sources of data, such as larger natural history studies or registries with outcome data, and use these to anchor your narrative. Where gaps in your understanding exist, consider engaging clinicians with specific and relevant experience for expert insight or advisory boards.

Engage with stakeholders

Make sure that stakeholder engagement is considered early and the value of their insights is maximised. Ask yourself key questions, such as: Do you have plans to engage with patient advocacy groups, or do you need to put this into motion? Can patient or clinician interviews provide qualitative evidence to address any key data gaps, and offer valuable insights? Could more structured expert judgement studies generate quantitative evidence to address key gaps or validate key assumptions?

Step 2:
Building Your Case

 

Start early

Whilst this is something we always recommend to our clients, it’s particularly important in rare conditions. Develop your dossier early to ensure evidence gaps (which can be flagged as placeholders throughout the document) are identified well ahead of launch, so there is sufficient time for further evidence generation by both global and local teams.

Evaluate disease awareness

If this rare disease has only recently been identified or knowledge of the disease is limited (e.g. it’s the first product to be launched in this disease), focus on what is essential for payers to understand to appreciate the value of the product. Tailor the level and extent of introductory content needed to fill any gaps in their knowledge, but don’t fall into the trap of an excessively detailed description of the disease.

Focus on the clinical- and patient-relevance

Trials in rare conditions frequently evaluate novel, disease-specific, surrogate or biomarker-driven endpoints, and payers may not appreciate the value of these unfamiliar endpoints. The value dossier narrative should emphasise the importance of these outcomes, using examples where similar endpoints have been validated in related conditions, to demonstrate why they are clinically meaningful and/or patient-relevant. Engagement with clinicians and patients could further validate the relevance of these endpoints.

Build on existing precedent

Evidence bases for rare diseases come with higher levels of uncertainty. Whenever possible, reference precedent set in reimbursement appraisals within the disease or related diseases to support the evidence you present. For example, were other trials in the same condition non-RCTs? If the drug’s mechanism of action is particularly complex or novel for the given indication, can you reduce payer uncertainty by comparing it to similar drugs used in different indications?

Step 3:
Follow-Up Investigation

You’ve developed the early version of your value dossier, but there are a number of sizeable evidence gaps remaining. How do you strengthen your dossier? Regular updates are important for all value dossiers. However, given that the evidence base in a rare disease is often rapidly evolving, regular dossier updates to reflect new evidence are particularly important for rare diseases. In these updates, consider including data from early access or compassionate use programs, updated registry analyses, long-term data cuts, or evolving insights from local affiliates. As engagement with local stakeholders evolves, continuously identify where patient quotes or clinical testimonies can be collected and incorporated into the narrative to emphasise the value of the treatment.

In Summary

Crafting a successful value dossier for a rare disease demands meticulous and early planning, proactive evidence generation, and effective stakeholder engagement. By addressing these key considerations, you can overcome the complexities and challenges in the evidence base, and make a strong case for the value of your new rare disease treatment.

If you would like to discuss the above approaches in more detail, or how Costello Medical can support you with an upcoming value dossier, please do not hesitate to contact Issy Newell, Deputy Head of Rare Diseases (LinkedIn). This article was written by Issy Newell with support from Juliet Johns (LinkedIn). The views/opinions expressed here are their own and do not necessarily reflect those of Costello Medical’s clients/affiliated partners. Issy Newell and Juliet Johns are employees at Costello Medical.

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