Jan 1, 1970 - Jan 1, 1970,

RWE: A new hope for rare disease

RWE shows great promise in helping accelerate treatments for rare disease

Rare disease treatments are, by their nature, complex to develop and launch. But in recent years these diseases – broadly defined as being of low prevalence, chronically debilitating and without satisfactory treatment – have been gaining more attention from pharma companies.


Of the record 59 drugs the FDA approved in 2018, almost 60% were orphan drugs, increasingly developed with a different approach to traditional pharma routes. 


“A randomised clinical trial (RCT) is not always going to be a feasible way to address a research question in rare disease because there’s typically a smaller community of patients,” says Sonal Bhatia, Vice President, Medical Affairs Rare Disease at Pfizer. “When it comes to rare disease you need real-world evidence (RWE).” 





In short, RWE is proving crucial in demonstrating the benefits of new molecules, in shaping trial design and in measuring the long-term safety and efficacy of a product.



“Typically for rare disease you’re entering a space where there’s no standard of care or treatment,” says Dirk Vander Mijnsbrugge, Senior Regional Medical Affairs Director Europe at Pfizer. “It is really important to understand the natural course of the disease, to understand how impactful you can be with your medicine and develop a really targeted development plan. Here RWE is of the essence.”


The regulators are also increasingly supportive. The FDA and the EMA both recognise that rare disease calls for a different approach, including both smaller sized trials and ongoing RWE generation. 


Drowning in data

Generating useful RWE insights is, however, anything but straightforward and pharma is still working to map out the best way forward. It is a complex undertaking involving multiple bodies that comprise the RWE ‘ecosystem’, including regulatory agencies, payers, clinicians, patients and health technology assessment agencies (HTAs). 


Added to that are the numerous measures of interest – treatment patterns, adherence or compliance, comparative effectiveness, long-term safety or patient-reported outcomes (PROs) – and the wide variety of methodological approaches available, including database analyses, medical chart reviews, artificial intelligence (AI), registries and observational studies. 


“The danger with data is that there’s too much,” says Bhatia, pointing to retrospective data, such as primary chart reviews, medical claims data and electronic medical records, as well as prospective data, such as pragmatic trials or patient and population surveys.






The relatively small patient populations in the rare disease space, coupled with the immense amount of noise in ‘messy’ data, makes it important to establish targeted, standardized and validated approaches to developing fit-for-purpose datasets, says Jennifer L. Wong, Head, Real World Evidence, The Americas at Sanofi. “Being laser-focused on solving the key scientific or clinical questions with the appropriate data, methods and agile approach is of paramount importance.”



Clinicians are making progress. One source for rare disease data that is proving especially valuable comes in the form of patient registries, says Bhatia. Real-world, observational and hypothesis-generating, they show the lifecycle of a disease over time, highlighting patterns, needs and the variability of clinical progression.  


“The value of registries is to understand what’s happening in clinical practice and validate what you really believe are those unmet medical needs, the true progression of the disease, the treatment and how it’s being utilised by physicians,” she says. “This gives us a better insight on the appropriate endpoints that are going to be of value to the patient once the drug gets approved.”


Escaping siloed practices

However, creating new registries and databases can be costly and they can be challenging to maintain, and expand beyond their original purpose. “We should always think beyond a one-time solve,” says Wong. 


Every stakeholder’s aim, says Wong, should be to “leverage innovations in data science, advanced analytics and digital technologies – and build alliances. We need to collaborate across the community to learn and harness the collective wisdom, especially to reduce data and organisational silos and maximize the value of all that already exists in the real-world.”


“Trust, traceability and transparency are the priority in the adoption and acceptance of RWE,” says Wong. “The most important things are the reliability, validity and reproducibility of the data and methods used.”


There’s much work to be done here. Siloes are very much in evidence with different stakeholders favouring different data and methodologies, Vander Mijnsbrugge has found. 

For example, patient groups typically attach more value to PROs than other groups while institutions and payers value post-comparison or effectiveness more than regulatory authorities do. 


The method of RWE collection affects acceptability too, with most stakeholders attaching high value to observational studies and registries, while pragmatic clinical trials and non-interventional studies are also highly rated for collecting information on safety and comparative effectiveness. 


RWE procedures vary considerably. “We still see different policies across multiple European countries on how RWE is being judged, respected and valued,” says Vander Mijnsbrugge. “Payers see the value of it, they need it to do their cost modelling, but the policy for using RWD is not yet as well established.” 


Engaging with patients

To succeed in generating useful RWE for rare diseases pharma will also have to engage deeply with patients and patient advocacy groups. By engaging patients early, valuable insights shape strategy from the outset and can continue throughout the lifecycle, building in efficiencies and ensuring appropriate RWE is being collected that reflects the reality of day-to-day life of those living with disease. 






“Early engagement with patients and patient organisations is really critical, not only for your clinical trial development plan but also your evidence plan in addressing the needs they have,” says Vander Mijnsbrugge. “We engage as soon as we have the first idea, asking patient groups what type of evidence we should collect. When you bring the medicine to market, it’s then addressing their needs, not only the FDA or payer’s needs.”



Furthermore, insights gleaned from patients and registries can shine a light on the diversity of experience among disease populations, says Bhatia. “In rare disease especially I have noticed that many patients have a completely different patient journey, all ending in the same diagnosis.”


An end in mind

When it comes to developing effective RWE rare disease programmes, it is also useful to start with the end in mind, says Bhatia. “There was a time when we would create RWE, develop and publish it and then say, ‘What should we do with it?’ I don’t think that’s the right path anymore. 


“We need to think about who the patient is, what the payer wants in order for us to be able to bring this product to market, what type of data is going to have the most impact and then work backwards with that end customer in mind so that we can really generate the right data.”


For Vander Mijnsbrugge, this means developing a RWE strategy in tandem with a clinical development programme. “Right from the start these go hand in hand – the two are extremely complementary. It’s also important to really look at RWE as an enabler throughout your entire lifecycle development.”


Clearly there is work to be done but the direction of travel is getting more clear and promising every day. Thanks in part to the permissive approach to RWD in the 21st Century Cures Act and the anticipation of the FDA’s issuance of draft guidance on RWE in 2021, there is a “hunger and thirst to explore RWE in the US”, says Wong. 


“It is exciting to see more and more multi-stakeholder, cross-disciplinary public-private consortiums and coalitions coming together. We may be looking at a new world order of drug development and regulatory approvals. Our patients deserve it.”

Jan 1, 1970 - Jan 1, 1970,