Illuminating a Rare Disease: It is More than a Number
200,000. That’s how a “rare disease” is most often distinguished from a “common disease” — 200,000 or fewer people need to be affected for a particular disease to be rare, officially, in the United States. The number triggers many benefits for rare disease patients, but it also triggers some generalizations of rare diseases, which can obscure important issues. Thus, while 200,000 enumerates rare diseases, it fails to illuminate rare diseases.
Why is 200,000 considered the cut off point to distinguish a rare disease from a common one? Surprisingly, the number 200,000 was an afterthought. No prevalence number was attached to the original Orphan Drug Act signed into law in 1983. But, Congress found it needed a prevalence number to clearly distinguish rare disease and so it made 200,000 that number in a bill passed the following year. How Congress landed on 200,000 is not easily traced. However, I frequently hear people who were close to the early legislative efforts behind the Orphan Drug Act tell the same story about how patient advocates involved in the original bill suggested that multiple sclerosis be used as a benchmark for establishing the upper border of rare disease prevalence. At that time, 200,000 people had multiple sclerosis in the United States. The number hasn’t changed since.
So, 200,000 it is. As arbitrary as the number may seem, the distinction is important, at least at the macro level. Powerful business incentives exist to entice drug developers to invent and market new treatments for patient populations no larger than 200,000. Scientists and patient groups get special attention from rare disease offices and operations within the U.S. Food and Drug Administration and the National Institutes of Health when they focus their attention on diseases affecting fewer than 200,000. Professional societies and health care organizations interested in rare diseases set their sites on those with prevalence estimates below 200,000.
Yet, while the 200,000 prevalence figure is important for legal, regulatory, and programmatic purposes, prevalence alone is woefully inadequate to reveal micro level attributes of rare diseases and rare disease communities. Designating a single number to delineate rare diseases generates an impulse to aggregate all rare diseases together as if they are the same, because, after all, they all have a prevalence of less than 200,000.
Bottom up vs top down enterprises
One consequence of aggregating rare diseases under this one number is that justifications for any special accommodations are linked to the single attribute rare. In many cases, however, just rare is insufficient. Take, for example, claims rare disease constituencies may make for special accommodations, such as research funding, clinical training, coverage policies, and patient education. Many common diseases have a similar claim on these accommodations, and thus a prevalence of less than 200,000 will not be persuasive. However, rare disease can be distinguished beyond the prevalence aggregation. Consider how rare disease is by and large a bottom up enterprise. That is, advances in rare diseases often start with the affected patients, families, and communities. The people leading rare disease efforts often do not come from the life sciences. They come to the rare disease from other realms, like business, education, trades, and home. They come to it from necessity and urgency, not from a primary interest or advanced training in the life sciences. They organize patient groups, establish research programs, find clinical centers, push for legal and regulatory reforms, and educate patients, health care providers, payers, and regulators. They do all this mostly on their own wits and determination.
Patients with common diseases contribute to advancements to be sure; however, they can rely on professional managers, experienced scientists, and others who come to those diseases through an interest and training in life sciences to lead the way. The support structures of well-established, large, common diseases take on the forms and functions of institutions: they are top down enterprises in effect. Think of diabetes, cardiovascular diseases, and cancer, for example. As a result, there is often a big gap between rare diseases and common diseases in resources and wherewithal that give rare diseases their claim for special accommodations. In this respect, the distinction between rare and common diseases is better understood as the distinction between bottom up and top down support than between more or less than 200,000 affected people. Characterizing rare disease is this way is much more powerful than leaning on prevalence alone.
All rare diseases are rare, but all rare diseases are not alike
The aggregation of rare diseases based on the 200,000 prevalence number also obscures the considerable variation that exists among rare diseases. Differences can be appreciated in the pathophysiological basis and clinical manifestations of rare diseases, age groups affected, and the experience, capabilities, and wherewithal of rare disease patient advocacy groups among other important attributes. The degree of help needed in particular rare diseases ranges considerably. For some rare diseases the science can be well developed, research well funded, clinical support well established, and advocacy well organized and supported. Rare diseases of this nature can take on the top down, institutional attributes of large, common diseases. On the other end of the continuum are those rare diseases for which there are very few researchers and little funding to find more, a dearth of clinicians who can diagnosis and treat them, and advocacy groups too new and inexperienced to advance their causes boldly and quickly. And, then there are the rare diseases that fall all along the continuum between these extremes. Looking past the aggregation of rare diseases based on the prevalence threshold could enable better matching of needs and support, and also more efficient and just resource allocation.
Aggregating rare diseases under the single prevalence number can have its own effects on the rare disease community itself as well. It could shield them from seeing how the heterogeneity within the community can generate obligations among them. For example, perhaps highly evolved and sophisticated rare disease groups should consider how they can help other less advanced groups (i.e., exhibit some noblesse oblige), or at least how they can be sure not hinder their progress (i.e., avoid tragedy of the commons).
Seeing through the prevalence veil
When we illuminate rare disease, we can see much more than what the statutory prevalence distinction shows. We can see that claims the rare disease community makes for accommodations are not based on just smaller patient populations, but rather on patient populations that are at a decided disadvantage compared with larger, common diseases with support structures that are institutional in scope and size. We can also see the heterogeneity across individual rare disease communities, which could enable more just and efficient resource allocation. Enumerating rare diseases is important to distinguishing them, officially, illuminating rare diseases is important to understanding them, thoroughly.