Understanding patient advocacy – the Rare Epilepsy Landscape Analysis (RELA)

The Rares. The increasing number of genetic diagnoses in rare epilepsies has resulted in the formation of a large number of non-profit organizations and support groups over the last decade.  These support organizations for rare epilepsies (“Rares”) have already had an important impact on the epilepsy genetics field. However, the overall impact, direction, and needs of the Rares have never been assessed systematically.  In a recent editorial, Ilene Penn Miller summarized the findings of the Rare Epilepsy Landscape Analysis (RELA), which surveyed 44 advocacy and support organizations for rare epilepsies.

Figure 1. The landscape of rare epilepsy support organizations in the US (adapted from the Rare Epilepsy Landscape Analysis, Penn Miller 2020)

Defining Rares. The Rare Epilepsy Landscape Analysis (RELA) defines “Rares” as rare epilepsy disease focused 501c3 nonprofit organizations and support groups, a definition that I will also use throughout the blog post. While conceptualizing this post, I had already learned that using the term patient organizations is often misleading and somewhat incorrect. In a recent editorial published in Epilepsy and Behavior entitled “Raring for Change: Confluence of Scientific Discovery and Advocate Alignment Warrants New Investments in The Epilepsies”, three main factors have been highlighted that are relevant to understanding the ecosystem of rare epilepsy support organizations. In this blog post, I would like to summarize some of these aspects. However, I realize that I am not doing justice to the full scope of the RELA Analysis and Appendix, and have therefore included the links to the Epilepsy Foundation website (link).

1 – The changing landscape of rare genetic epilepsies
Over the last two decades, rare genetic epilepsies have been transformed from a group of poorly understood disorders to well-defined disease entities, often with specific genetic etiologies found as the underlying cause. This transformation has spurred the development of precision medicine approaches. However, despite the fact that strategies for the development of targeted therapies are happening in parallel, the RELA recognizes that a common framework and approach to rare epilepsies is still missing. As of 2020, most rare genetic epilepsies do not have standardized guidelines for diagnosis and treatments, and there is no infrastructure for natural history studies or even retrospective approaches such as comparative effectiveness research, head-to-head comparisons of active treatments in real-life clinic populations to inform care tailored to the characteristics of individual patients. Accordingly, the rare epilepsy space does not only have a treatment gap given the lack of precision therapies, but also an infrastructure gap that may become apparent once the effectiveness of novel or existing therapies is studied. In summary, the diagnostic landscape has significantly changed, but both infrastructure and therapy development are lagging behind according to the RELA.

2 – Common challenges across the rare epilepsies
Most Rares foundations have been motivated by a lack of information, community, treatments, and research for the condition. Common challenges of the advocacy organizations that are largely staffed by volunteers were the (a) difficulties of connecting to specialty care, (b) the lack of natural history data, and (c) the discrepancy between research promise and research funding. With regards to access to care, the overall impression by advocacy organizations requires the medical community to take a close look in the mirror. Rares are concerned about collaborations between healthcare providers, territorial behavior, and unwillingness to learn beyond the focus of one’s practice. Such concerns are especially relevant for rare diseases, where patient communities are geographically dispersed. The lack of natural history data and a lack of an understanding of the overall burden of rare epilepsies was also recognized by the RELA. In total, 20 Rares had maintained disease-specific registries in the past, and the editorial by Penn Miller highlighted that this has generated a complex and costly landscape of disconnected registries despite the hope that these registries may provide benefit in tracking outcomes, accelerate approval of novel drugs, and support research.

3 – A consensus about high priority areas
The RELA analysis found a striking consensus between Rares with regards to high priority initiatives, including (a) transforming care, (b) improving disease understanding, (c) increasing research, and (d) translating interventions into clinical practice. A commonly shared challenge was the rapid access to multidisciplinary experts. The RELA analysis identified high-priority recommendations for the formation of multidisciplinary clinics or Centers of Excellence, development of Quality of Life scales for patient-centered trials, establishing guidelines for management, and provider education. The editorial suggests a National Registry for rare epilepsies following the model of the Rare Epilepsy Network (REN) that incorporates concepts for standardized outcome measures and quality improvement as pioneered in the Epilepsy Learning Healthcare System (ELHS) and the Pediatric Epilepsy Learning Healthcare System (PELHS).

What you need to know
With more than 40 rare disease patient advocacy organizations (Rares) responding to the RELA, the results of this study are reflective of the overall opinion of the rare epilepsy community. With up to $10 million combined annual private research investment, Rares are not only an important factor in rare disease research by providing the advocate perspective, but are an important driver of research. However, the private research investment is small compared to the annual >$150 million funds awarded by NIH. By emphasizing strategies to overcome the treatment gap through infrastructure for natural history studies, highlighting common challenges such as the need for collaboration between multidisciplinary providers, and recognizing strategies to overcome common challenges including Centers of Excellence and developing Quality of Life scales, the perspective of the Rares are invaluable to guide future directions in the rare epilepsy space. The perspective of the Rares will undoubtedly factor into the revised NINDS Epilepsy Research Benchmarks (link) and the overall strategies by which outcomes in rare epilepsies will be evaluated.

Finally, I would to thank Ilene Penn Miller in assistance with writing this blog post. Ilene is the current volunteer Director of the Rare Epilepsy Network (REN), a network including 50+ rare epilepsy organizations. She also serves as the Advocacy Co-Chair on the 2020 NINDS Curing the Epilepsies Conference (link).

Ingo Helbig is a child neurologist and epilepsy genetics researcher working at the Children’s Hospital of Philadelphia (CHOP), USA.