Addressing Diagnosis Challenges in the Rare Disease Space

Patients with rare diseases often visit several physicians over the course of many years before they receive diagnoses for their conditions—and that’s if they ever do. Delay in diagnosis continues to be a serious issue of all stakeholders involved in the rare disease space.

In a session presented today, October 15, 2018, at the National Organization for Rare Disorder’s Rare Diseases and Orphan Products Breakthrough Summit (NORD Rare Summit 2018) held this year in Washington, D.C., William A. Gahl, MD, PhD, clinical director of the National Human Genome Research Institute at the National Institutes of Health (NIH), and colleagues discussed the many diagnostic challenges that plague the rare disease community and ways to reduce time to diagnosis in these patients.

Dr. Gahl sat down with Rare Disease Report^® for an exclusive interview in which he discussed the session, the issue at hand, and proposed ways to solve the diagnosis challenge in the space.

RareDR^®: Can you tell us a little about the session you participated in this morning?

William Gahl, MD, PhD: This morning, we talked about diagnosis and how difficult it is. There were issues that were germane to individual diseases and then issues related to patients who have undiagnosed diseases in general. People talked about how difficult it was to find the appropriate diagnostician and I spoke a bit about how the Undiagnosed Diseases Program addresses those issues by receiving medical records and reviewing them with experts and then seeing some of the patients at the NIH, and now, at different centers around the country.

What are some challenges associated with rare disease diagnosis?

Financial difficulties with undiagnosed patients are enormous; that is to say, insurance companies are often unaware of how important a certain diagnostic test is, or, for example, if you wanted to get generic genetic testing—with an exome or a genome or some such—at least until recently, it was very difficult to do that because the insurance companies’ approvals are based upon specific diagnoses and the specific testing for that diagnosis. And so, to have what we call agnostic testing like that, it’s really difficult to get support for that from insurance companies. That’s actually getting a little bit better now.

But scientifically, our patients have run through an enormous number of tests already, and they’ve seen many, many experts, and no diagnosis has come to the fore—that means that this is either an extremely rare disorder, an atypical presentation of a rare disorder, or it’s a new disease. And when that happens, it’s very difficult to try to tie a particular genetic variant in with a particular presentation or clinical phenotype.

You need to have experts who have enough time to devote themselves to this and that’s actually not a part of the current medical paradigm in this country. Which is to say that there’s a business model that’s associated with physicians and other caregivers spending relatively little time with patients and being reimbursed for seeing a large number of patients. And so, one has to sort of exclude oneself or exclude these patients from that paradigm and allow for a considerable expenditure of time to invest in the undiagnosed disease.

How can health care providers overcome some of these challenges?

Physicians need to recognize when a disorder or presentation is unique, and they need to refer appropriately. Going to specialists and defining which specialists to go to, is something that providers have to do. But then there’s another step, and that’s at the level of the expert or the consultant, and at some point, if that consultant doesn’t recognize this as a particular disorder, then we do have the Undiagnosed Diseases Network in this country now that provides essentially free diagnostic evaluations for people at, now, 12 different sites around the country. That should be the next step when all diagnostic avenues have been exhausted by specialists at medical centers, and we just need to increase awareness of that.

What’s your take-home message for patients and providers?

One of the overriding themes here is that individuals who have rare diseases—especially undiagnosed diseases—are incredibly desperate; they want to share their stories, and they do so with social media. They need to have a community and they can establish a community like that through social media. They need advocacy groups and then they need a champion within the medical community to bring to fruition some of the studies that need to be done in order for interventions.

I think we all need to recognize that there are an awful lot of rare diseases—there are thought to be 25 million rare disease patients or people who are influenced by rare diseases in the United States—and all of us probably have someone within our network who has a rare disease. We need to be empathetic to those folks and not abandon them as a medical profession just because we don’t know enough about the disease.