Clinical Pathways Improving Management of Rare Conditions

Rare disease treatments seem to be everywhere today despite the fact that to be considered rare, a disease must affect <200,000 patients and <7000 patients to be considered ultra-rare.^1,2 The US Congress created this definition when it passed the Orphan Drug Act of 1983. Rare diseases became known as orphan diseases because pharmaceutical companies were not interested in adopting them to develop treatments. The Institute for Clinical & Economic Research (ISPOR) has been instrumental in working to foster an environment with improved access to treatments for rare conditions.

ISPOR describes itself as the leading global professional society for health economics and outcomes research (HEOR). Its mission is to improve decision making for health by promoting HEOR excellence. ISPOR has stated that because of the small patient population that is inflicted with rare conditions, it is not possible for pharmaceutical companies to recoup development costs unless prices exceed those that would be commensurate with traditional cost-effectiveness thresholds.

ISPOR believes that these factors are operative for drugs with populations >10,000 patients. To assure development and access of treatments for rare conditions, the Orphan Drug Act created financial incentives to encourage companies to develop new drugs for rare diseases. The rare disease definition is used to establish the conditions that qualify for these incentives.

Based on the definition of rare conditions, a 1 million member plan is likely to only have one patient with a rare condition. And a primary care provider with only 2500 patients is unlikely to see one patient with a rare condition over their career. As such, rare is rarely on anyone’s radar. However, the impact of rare diseases is significant when one examines rare disease collective. Around 350 million people, or the population of the United States, worldwide are affected by a rare disease.³ In the United States, there may be as many as 7,000 rare diseases, affecting about 30 million people or slightly <10% of the population.⁴ As such when taking in its totality, rare conditions are not so rare. 

From a clinical basis, rare diseases typically are severe in their morbidity and mortality. Despite significant clinical need, there are most often large gaps in treatments because rare diseases historically have not supported large investments, although discoveries in gene science and financial incentives is changing that. The majority of rare diseases are thought to be genetic, directly caused by changes in genes or chromosomes. In some cases, genetic changes that cause disease are passed from one generation to the next. As a result, for scientific and financial reasons, new therapies are coming to market on a regular basis to treat rare diseases. 

However, several things have not changed, but need to. For starters, simply diagnosing rare diseases most often is delayed. This in part is due to physician training that is based in part on the mantra: “If you hear hooves, think horses not zebras.” In a world of medical practice built on memorization, physicians are forced to play the odds, which of course, are  that patients are more likely to suffer from common conditions rather than rare ones. 

This thinking always contributed to a delay in the diagnosis of rare diseases, the impact of COVID-19 has increased this delay. Cancer screening rates plummeted during the first year of the coronavirus pandemic, a new survey revealed.⁵ In addition, patients are being diagnosed with more advanced cancers than they were before the pandemic, according to the American Society for Radiation Oncology.⁶ 

There are, of course, opportunities to improve the diagnosis of rare diseases. Clinical pathways can play a role by directing physicians to rare conditions to consider within diagnostic pathways of more common conditions. Education efforts on rare conditions can do the same by including their call out when describing differential diagnosis of more common conditions or grouping several rare conditions together for an education session that would have more impact on a physician’s practice.

This of course can be improved through education and use of machine learning. Systems have been developed that can analyze big data to earlier identify patients with rare conditions, alerting physicians of the possibilities and developing predicting patient personas to best target care.  This application programming interface- driven automated intelligence and machine learning technologies, complemented with wrap-around data science services and subscription-based offerings, can integrate and feed alerts to downstream systems. This data can be used to drive educational programs. Programs designed to combine several rare diseases or focus on a broader hot topic making it worth’s a physician’s time.

Finances of rare disease are a challenge as well. One potential change is Medicare for More instead of Medicare for All, which remains politically impossible. In 2001, Congress passed landmark legislation to add amyotrophic lateral sclerosis (ALS) as a qualifying condition for automatic Medicare coverage. The regular 24-month waiting period was eliminated for ALS patients receiving Social Security Disability Insurance. Medicare eligibility now begins simultaneously with cash benefits, approximately 5 months after an individual gains Social Security disability status. Just as ALS has been granted immediate access to Medicare coverage despite a patient’s age or length of disability, Medicare could immediately cover other rare diseases.

This would alleviate the burden in patients and payer as well as make the payer HEOR cases easier as there would always be just Medicare as the payer. This would eliminate the issue of gene therapy and others that have a large single payment despite the benefit paying out over many years, across potential health insurers. Until that occurs, rare diseases are an ideal area for value-based contracting based on outcomes. So, given the increase in rare disease treatments there are many opportunities to assist all stakeholders to improve both clinical and financial outcomes.

Clinical pathways have a unique opportunity to improve the diagnosis of rare diseases, in addition to their role in treatment. The use of artificial intelligence can provide an individualized patient-centered approach which is missing from the traditional paper clinical pathways. As clinical pathways become more sophisticated, tackling the increasing number of treatable rare conditions may be within reach. 

Afiliation: EVERSANA™, Berkeley Heights, NJ

Disclosures: Dr Stefanacci is the chief medical director for the managed markets agency of EVERSANA™