When the Purcells brought their new baby, Trey, home from the hospital, he was a seemingly healthy newborn. But he quickly began to develop a series of health complications. After several tests, at the age of two Trey was diagnosed with Hunter syndrome, a rare, inherited genetic disorder that affects the body’s metabolism, leading to poor physical and mental development, that affects organ function and results in other complications.
While Hunter syndrome is rare, the experience of the Purcells is not so uncommon. Defined by the World Health Organization as any disease that affects less than 1 in 2000 people, there are about 7,000 known rare diseases with more new rare diseases being identified every year. Some estimates suggest that as many as 1 in 12 Canadians may have a rare disease, though many of them will not present with serious symptoms.
“A rare disease is rare, but having a rare disease is not,” explains Dr. Larry Lynd, a CHÉOS Scientist and Director of the Collaboration for Outcomes Research and Evaluation (CORE) at UBC.
The story of the Purcells comes from Million Dollar Meds (www.milliondollarmeds.ca), a collaborative project between the UBC Graduate School of Journalism and the CIHR New Emerging Team for Rare Diseases led by Dr. Lynd, whose body of work has largely focused on understanding rare diseases using a health economics approach.
This award-winning multimedia project was launched to share the stories of families like the Purcells and the struggles that come along with living with and caring for people with rare diseases. This project ultimately culminated into a CBC Ideas documentary which was a discussion and debate among researchers, patients, clinicians, and policy makers.
Getting a Diagnosis: Access to Genetic Services
However, even getting a diagnosis from a genetic specialist can be difficult to access, due to geography and growing wait times.
While the Purcell family was able to get a diagnosis relatively quickly, many children and adults can spend years enduring test after test to eventually discover that a rare disease is at the root of their suffering. Dr. Lynd calls that lengthy journey a “diagnostic odyssey”.
In the CAUSES Study, in collaboration with Drs. Jan Friedman and Alison Elliott at BC Children’s Hospital, Dr. Lynd and his team did an evaluation performing whole genome sequencing in children who appear to have an undiagnosed genetic disorder. The team then estimated the cost difference of doing early whole genome sequencing compared to the cost of the diagnostic odyssey, which include both medical costs as well as the financial burden on families for travel, caregiving, and work loss.
“We found a genetic diagnosis in about half of the kids. Avoiding these 5-, 10-, or 15-year diagnostic odysseys by using whole genome sequencing as a first-line test would actually save money for the health care system, and for families,” said Dr. Lynd “Historically, whole genome sequencing hasn’t been used in this way and our research shows that even though it is expensive, it is actually more efficient in some patients.”
Even if there isn’t a treatment for the disease, a diagnosis can get families access to other programs, services, and funding, as well more effective treatment to help with symptoms, he added.
Dr. Lynd is now looking at the clinical implementation of genome-wide sequencing in adults and the potential impact of this approach as the Health Economics Lead for the GAPP Study.
“Here we’re applying the findings from the CAUSES Study into a clinical setting and an older population and looking at how provision of genetic services could work in the real world,” he explained.
But while early whole genome testing seems like an easy win, he adds one of the biggest issues facing many countries is access to genetic services.
“The current wait time to see a genetic counsellor or clinical geneticists in B.C. can be up to 2 years or more, which requires travel to the Lower Mainland,” he said. “Those years in limbo can affect the access people have to other treatments and means they may continue to seek out other specialists. This can also affect family planning decisions around whether or not to have other children.” In response to these challenges, Dr. Lynd is also co-lead on GenCOUNSEL, a project funded by Genome Canada and Genome BC that is evaluating the Canadian capacity to provide clinical genetic services.
Cost of treating rare disease continues to rise
Beyond his work with Million Dollar Meds, Dr. Lynd and his team have been investigating the diagnosis, treatment, and management of rare diseases from a societal cost-benefit perspective, both currently and in future projections.
“Recent projections from the health minister indicate that by 2025, the province could be spending $125 million per year to treat a group of 250 patients with rare diseases. That’s about 7% of the provincial pharmacare budget,” said Dr. Lynd. “The drugs that are being developed for these diseases are getting more and more expensive and the burden on our health system grows. But on the other side, this needs to be balanced with the potential impacts on patients and families.”
Once diagnosed, Trey was put on a medication to treat his Hunter syndrome. At the time, this medication was the second most expensive drug in the world, at $3,500 per dose and an annual cost of over $700,000. This ignominious title has since been passed on to newer drugs that can reach up to $3 million per year, per patient.
“In the current profit-maximizing environment, drug makers are developing and releasing new treatments at increasingly high prices” notes Dr. Lynd.
In our publicly funded healthcare system, decisions about funding drugs for rare diseases like Trey’s are not made at the disease level, but at the individual patient level, says Lynd, who sits on BC’s advisory panel for rare disease funding. “These decisions are made based on each patient and the available evidence, in conjunction with expert clinician input.”
But he adds the cost of these drugs means that there is significant uncertainty about funding them because it’s not always clear whether or not a drug will work in a particular patient. On top of this, each decision to fund treatment for one person uses up healthcare dollars that could be spent elsewhere.
A series of trade-offs
“There is a significant opportunity cost to funding these expensive drugs,” says Dr. Lynd. “We can pay for them but then may not have enough money left over to put towards things like long-term care or the opioid crisis.”
Another important piece of the puzzle is the balance between treating the disease or treating the symptoms. Symptoms vary greatly from person to person and some people may not even realize they have a rare disease until later in life, if ever. For example, one patient also featured in the Million Dollar Meds project was only diagnosed with Pompe disease at age 69, after a slow onset of mild symptoms.
“Treatment for this disease costs about $1 million per year,” notes Dr. Lynd. “If that patient had been screened earlier in his life, it could be difficult to justify this expensive treatment without serious symptoms.”
These trade-offs lead to heartbreaking stories about patients in need who are denied access to treatment for their disease. “With the cost of these drugs, nobody is able to pay out of pocket for their treatment like they could for less expensive but unfunded drugs,” says Dr. Lynd.
In the end, taxpayers and private insurers (i.e., employers) are the ones paying for these drugs and decisions about rare diseases have to be made in the context of the whole healthcare system. Dr. Lynd and his team have conducted a series of studies to understand Canadians’ values when it comes to funding rare diseases. They found that Canadians prioritize the effectiveness and safety of a treatment as well as the severity of a disease.
“Decision makers need to integrate the public’s values into their reimbursement framework for prioritization of drugs,” he notes.
Ultimately, the astronomical cost of some of these drugs is unavoidable with the current way they are developed, says Dr. Lynd. New research is looking at different ways of incentivizing and funding drug development to avoid prohibitively expensive but much-need treatments.
There is also ongoing research of gene therapies that could potentially be a one-time treatment to cure certain rare diseases and bring relief to families like the Purcells.
“We don’t know what causes common diseases like asthma, depression, or hypertension so we can’t target the underlying source,” he says “In rare diseases, we have the opportunity to get to the root cause of a disease and find a solution.”