It’s no longer a luxury to treat rare diseases — we must act accordingly

I am a medical geneticist. Over the last 35 years, I have been privileged to work with patients and families with some of the most uncommon, rare conditions on the planet. In the past, there were only a handful of rare diseases we could accurately diagnose or effectively treat. And it often took years for patients to receive that diagnosis (if ever).  

However, two things have radically changed my field to both better diagnose and care for more rare disease cases. The first was the Orphan Drug Act (ODA) of 1983, which provided strong incentives for the development of therapies for orphan disease indications. The second was the completion of the Human Genome Project (HGP) in 2003. These major developments, coupled with the associated technological advancements they spurred, provided a new way to diagnose and treat rare diseases. 

We can now diagnose over 6,000 distinct conditions with accurate DNA sequencing, with a potential increase to over 10,000 identified conditions in the coming years. As our abilities to diagnose and treat rare disease has grown, our impact has started to become noticeable in medical economics. Notwithstanding, the existing payor and evidence systems are not well equipped to model rare diseases.

In rare diseases, there are many conditions with fewer than 100 patients, who are then further subdivided by their own unique genetic mutations, often with enormous clinical variation (called phenotype). So how does one design payment models, pricing models, public policy, outcome targets, evidence-based treatments and clinical trials with so few highly variable individuals? It is impractical or impossible to achieve the large numbers typically used for statistics acceptable as classic scientific proof. 

Given the powerful incentives of the Orphan Drug Act, pharmaceutical and biotechnology companies have rapidly expanded into rare disease product development. Still, the costs of these therapies highlight the denominator problem of rare diseases. 

A rare disease clinical trial is around half the cost of a common disease trial; however, the number of potential patients is exponentially less due to the nature of rare diseases. For rare diseases, the treatments being developed are typically considered life-altering/saving, while for more common diseases they may represent only an incremental gain. All of these factors make comparative cost/benefit analysis difficult for groups like the Institute for Clinical and Economic Review (ICER), a nonprofit organization that reviews clinical evidence and comments on the cost-effectiveness of treatment. Payors who often use and rely on such analyses ultimately have no clear source to go to for metrics in rare diseases. Therefore, the fallback position is typically denial of testing or treatment leading to lengthy and exhausting battles between families/physicians and payors. This system does not harbor ill intent, it is simply not well equipped to deal with the new reality of rare diseases.

Genetic sequencing has come to play a crucial role for patients, providers and drug developers alike. Beyond ending the diagnostic odyssey, genetic sequencing allows us to identify potential treatments or individualize treatment plans for patients, particularly in the fields of cancer and rare disease. Earlier treatment and eliminating more expensive diagnostic searches can improve patient care and satisfaction and reduce overall costs. According to my estimates, the current cost for a whole genome sequence and analysis sits around $2,000-3,000. For comparison, a routine MRI generally costs around $1,200. Genetic testing is coming in line with the costs of well-accepted diagnostic tests yet brings tremendous power.

Access to genomic sequencing varies depending on location and socioeconomic status. Despite the progress made in lowering the costs to conduct genomic sequencing, payor coverage remains a major barrier and pre-authorization a constant struggle. On an internally released survey we conducted at Children’s National, responses indicated that clinical geneticists and genetic counselors spend about 25-35 percent of their time on the authorization process alone, with no guarantee of success. That is unacceptable given how effective genomic testing has become in the last 20 years and the benefits of identifying a potential treatment it may lead to. We need to align our payor models with the advancements in the field.

Genetic testing has been on a continuously changing improvement curve and will be for the next several years. We need to start thinking of DNA and genetic testing as a combination of a classical laboratory test combined with a pathologist’s interpretation (board-certified molecular geneticists currently), rather than a research test. And we need to think that way in our payment and reimbursement systems as well. One potential answer to the dilemma of insurance barriers to genomic sequencing would be to grant board-certified medical genetics experts access to pre-approvals for both testing and the therapies that result from diagnosis. That would go a long way to addressing the high burnout rate seen in the field, which is causally topped by excessive administrative burdens.

We cannot treat rare diseases as luxury items where diagnoses and treatments are sparse and available only to a few or only the well-off. We need to make sure access to genetic diagnostics and therapies is available to all of our patients. Genetics is often cited as the future of medicine — we just need to fix the potholes in the road to get there.  

Marshall Summar, M.D.., is the division chief of Genetics and Metabolism and the director of the Rare Disease Institute at Children’s National. Hospital. He is a physician, clinical geneticist and researcher, best known for his pioneering work in caring for children diagnosed with rare diseases.