A Zebra's Trust: How Rare Disease Communities' Participation in Data Trusts' Governance Builds Trust and Drives Research.

• Author: Smith, Samantha C.

TABLE OF CONTENTS I. INTRODUCTION II. RARE DISEASES A. Understanding Rare Diseases B. Analysis of the Current Legal Frameworks 1. Global Legal Landscapes 2. Critiques of the Current Landscape and the Need to Emphasize Data 3. Small Data, Precision Medicine, and the Need for Data Sharing III. DATA TRUSTS A. Defining Data Trusts B. Case Studies of Data Sharing Initiatives 1. Breaking Barriers to Health Data 2. Other Rare Disease Data Sharing Initiatives 3. The EU's Move toward Broad Data Trusts and Usable Data IV. PROMOTING RESEARCH AND BUILDING TRUST A. Participant-Centricity B. Trust C. Building Trust through Good Governance D. The Role for Rare Disease Populations 1. Being Heard 2. Hesitancy toward Data Sharing 3. Active and Engaged Participation 4. Advocates of Needed Legal Structure V. CONCLUSION I. INTRODUCTION

On May 7, 2020, Lisa Cummings listed out the similarities: fear of the unknown, the way people stare, worry, isolation, and hope. With a click, she shared her post on Facebook's "TSC Alliance Tuberous Sclerosis Complex Discussion Group," highlighting the parallels between COVID-19 and her daughter's Tuberous Sclerosis Complex (TSC) diagnosis. (1)

Thirty-one years earlier, Lisa's daughter, Deborah Ann, or as her mother calls her, Dac, began demonstrating the symptoms of TSC at only six months old. (2) TSC, a rare genetic disorder that causes benign tumor growth throughout the body among other symptoms, (3) proved debilitating for Dac, as it does for the majority of the few individuals with this diagnosis. Dac grew up suffering from autism and epilepsy and survived multiple surgeries, a brain aneurysm, and a stroke. (4) Now thirty-one, Dac is, as her mother described on Facebook, "forever a toddler locked inside an adult body." (5) While Dac requires full time care from Lisa, Lisa in turn relies on the sense of community she finds in her Facebook "family" of other TSC patients and their communal hope for a cure. (e) This combination of community and hope is often the best that a rare disease patient or their caregiver can expect due to the lack of research and drug development in the rare disease space. However, in the modern age of data-driven medical discoveries, this same community could prove key to turning hope into progress.

When the world was overrun by COVID-19 in 2020, many across the world had their first experience facing the trials of a rare medical condition. As Lisa suggested on Facebook, it was a time to fear the unknown, to have people stare at the signs of illness (whether they be the physical symptoms experienced by a rare disease patient like Dac or the visibility of wearing a mask), to worry, to stay in isolation, and to long for normalcy. For many, it was their first time knowing the frustration of getting mixed information from experts, experiencing a condition about which experts knew little, and facing the fear of unknown treatments that lacked the confidence of withstanding the test of time. (7) However, for the roughly 6-8 percent of the world population that has a rare disease (8)--a population roughly equivalent in size to that of the United States (9)--these experiences remain unextraordinary, even daily, occurrences.

COVID-19's alarming transmission and resulting global impact spurred institutions around the world to share their data. (10) As a result, COVID-19 research teams benefited from international cooperation in data sharing, allowing for rapid developments in care and vaccinations. COVID-19 and the world's responsive demand for data thus serves as a poignant example of how data sharing can drive life-changing and life-saving research and outcomes.

In stark contrast to patients who have experienced COVID-19 and other frequently encountered medical conditions, the rare disease patient population suffers from a "small data" problem; their small numbers hinder the ability to study them and limit the market size from which funders can receive a return on their investment in research. (11) Data sharing is not only a benefit but often a requirement for successful rare disease research. While law and legal scholarship for rare diseases currently prioritize the affordability and marketability of cures and treatments in order to incentivize their development, little attention has been given to how the law can improve data sharing for the rare disease community in order to enlarge the available data sets and expedite research processes. The need to address rare diseases became a national priority in the 1980s and is once again gaining political traction, (12) but these new actions must reach beyond the previous success realized in domestic drug-development incentive programs to expand international cooperation and transnational coordination on data sharing initiatives and overcome rare diseases' small data problem.

Fortunately, data sharing is currently at the forefront of many legal conversations. As the world becomes increasingly data dependent, many countries are beginning to see data as a public good, (13) and government actions to increase the availability of data necessarily affect the rights of data subjects. Government programs like the European Union's (EU's) new data trust initiative, Trusted Secure Data Sharing Space (TRUSTS), aim to commodify data, depicting data sharing as a civic obligation. (14)

Data trusts are a promising instrument for data sharing but remain unsettled in their legal structure. While defined by the obligations between parties, data trusts lack a standard legal form. Even the TRUSTS project has identified a number of prospective legal problems without yet identifying its own legal structure. (15) Nevertheless, current scholarship seems to agree that, as their use increases, data trusts and similar data sharing programs will rely on the interrelated factors of stakeholder participation and trust to be successful. (16) As data trusts determine the nuance of their applicable law and legal structure, they should prioritize how their governance structures meaningfully involve participants to build long-term public trust throughout the data trust's lifespan.

This Note suggests that, rather than focusing on rare-disease-specific data sharing methods, crafting emerging large-scale data sharing programs like TRUSTS with an eye toward rare diseases will benefit both parties. Rare disease communities can harness the power of data trusts to promote cross-border research despite the current shortcomings in rare disease legislation, just as data trusts can welcome these communities' participation as a means to instill public trust in their evolving governance structure. Rare disease populations can benefit from decreasing the costs associated with current rare disease research and drug development--a goal largely beyond the scope of current legislative measures--while ensuring their voice and data are included in data samples intended for cross-sector use. Data trusts can benefit from the community oversight and cooperation of rare disease groups. These groups are regularly comprised of active, social communities uniquely situated to prioritize the success of both data sharing platforms and data protection measures, given their unique vulnerabilities from both constraints on sharing as well as privacy breaches.

Part II will describe rare diseases, the current focus of rare disease legislation, and how precision medicine will benefit from that legislation's structure, potentially exhausting the system to the point of making it ineffective in supporting cross-border research for both rare diseases and precision medicine. (17) Part III will address data sharing initiatives, focusing on the rise of data trusts, their nature, and the legal questions emerging from their structure. Part III will then turn to current data sharing initiatives, beginning with rare disease-oriented initiatives before addressing the EU's shift to broader cross-sector data sharing. Part IV will bring together these two matters to show the mutually beneficial relationship that can be formed through the rare disease population's role in data trust governance. Part V concludes by emphasizing that public trust in data sharing platforms revolves around a sense of personal data security in relationship to the benefits received from that data, and, therefore, any new system of governance requires ongoing monitoring to ensure that trust is well placed.

2. RARE DISEASES

   Understanding the impact current and prospective legislative and regulatory schemes may have on rare disease research relies first on understanding what constitutes a rare disease. The challenges present in defining and describing rare diseases indicate both how rare disease populations are disempowered and the unattractive market they present to investors. Their inability to create an attractive market serves as the hindrance to properly addressing rare diseases as the global health crisis that they are. However, these same features make the community strong in its interpersonal connections, its fierce advocacy for its interests, and its eagerness for innovation.

   1. Understanding Rare Diseases

      Defining rare diseases, which are also referred to as zebras (18) or orphan (19) diseases, is a complicated task because of the lack of sufficient data, scientific publications, and databases. (20) Although no universal definition exists, definitions found in legal frameworks, such as those described below, generally rely on prevalence thresholds: rare diseases are those diseases that affect 1 person in 500,000 thousand (0.0002 percent) to 1 in 2,000 (0.05 percent) of a state's population. (21) This reliance on point prevalence serves in large part to recognize the market hurdles facing rare diseases. (22)

      An estimated five thousand to eight thousand (23) rare diseases affect an estimated 300 million people. Some rare diseases are recognizable, such as sickle cell disease with its frequent presence in biology textbooks, or...