The Rare Disease Education Gap
Approximately 1 in 10 patients seen by the average physician in the United States may have a rare disease.
Summary
There are at least 7,500 identified rare diseases, affecting about 30 million people in the United States.* That means that approximately 1 in 10 patients seen by the average physician in the United States may have a rare disease. But often neither the doctor nor the patient knows it.
Because the number of people affected with an individual disease is relatively small and the number of rare diseases is so large, the average healthcare professional is unlikely to consider that an individual patient may have a rare disease. The challenge of diagnosing rare disease patients is further complicated by the fact that so many of the symptoms that rare disease patients exhibit overlap with symptoms that are similar to many of the common conditions that physicians see every day.
For decades, medical students and residents have been taught the phrase “when you hear hoofbeats, think of horses, not zebras”, rightly indicating that the symptoms that appear most commonly in their clinical practice are usually the result of relatively common conditions, not the rare syndromes that they may learn about in training. That training is reinforced by years of clinical practice, which provides healthcare professionals with consistent reinforcement that most sets of symptoms they see – and most test results – are indicative of common conditions.
The result is that, on average, the journey that rare disease patients and caregivers go through to get an accurate diagnosis takes 4-8 years, and the average time it takes for rare disease patients to receive an accurate diagnosis is 4.8 years (1). This “diagnostic odyssey” is a hallmark of the rare disease patient and caregiver experience, and clear evidence that there is a gap in rare disease education that must be addressed if the diagnostic journey is to be improved.
*Many sources indicate that there may now be more than 10,000 rare diseases
40 Years of Progress
The plight of patients with many rare diseases has greatly improved since the passage of the Orphan Drug Act in 1983. The act made drugs, vaccines, and diagnostic agents able to qualify for orphan status if they were intended to treat a disease affecting less than 200,000 American citizens. In order to encourage the development of drugs for orphan diseases, the act also included a number of incentives for biopharma companies, including seven-year market exclusivity for companies that developed the orphan drug, tax credits equal to half of the development costs, and accelerated approval of drugs indicated for rare diseases. Since 1983, more than 600 orphan drugs have been approved by the FDA (2). Still, there remains a major unmet need for patients with rare diseases – only about 5% of rare diseases have an FDA-approved treatment.
Significant progress has also been made in the diagnosis of diseases over the past several decades. Newborn screening of many genetic diseases is performed in all 50 states. Each year, millions of babies in the U.S. are routinely screened, using a few drops of blood from the newborn’s heel, for specific genetic, endocrine, and metabolic disorders – most of which are rare diseases. But much more needs to be done. In most states, only about 60 diseases are part of the regular newborn screening process.
Genetic testing for rare diseases that are not screened for at birth is also accelerating the diagnostic process, but they are underutilized in the screening and diagnosis of rare diseases. There are now more than 77,000 genetic tests currently in use, representing more than 10,000 unique test types, and many others are being developed (3). The largest number of tests utilized are prenatal tests, with the next largest group of tests are those used to define genetic alterations in cancer. Although the use of genetic testing for rare diseases is increasing, they make up a relatively small percentage of genetic tests that are performed.
An estimated 80% of rare diseases are believed to have a genetic origin. Advances in genetic testing, such as next generation sequencing technologies (NGS) and whole exome sequencing (WES ) have positively impacted the likelihood of obtaining the molecular cause of rare and undiagnosed diseases. These technologies have accelerated the diagnosis for an increasing number of undiagnosed rare disease patients, but their use is still related uncommon.
Despite advances in diagnosis and treatment, the overwhelming majority of rare disease patients still take many years to find out what is actually wrong with them. The underlying knowledge to diagnose them is often available, tests that can provide valuable information could be performed, and potentially life-changing genetic tests could be ordered. But if healthcare professionals don’t think to order the right tests or refer the patients to an academic center, patients and caregivers will continue to struggle to find what is actually wrong with them.
The Diagnostic Odyssey
Definition: a long wandering or voyage usually marked by many changes of fortune
Source: https://www.merriam-webster.com/dictionary/odyssey
For the average rare disease patient, the time between the onset of initial symptoms and an accurate diagnosis is often many years, with estimates ranging from 4 to 8 years for the “average” rare disease patient to get an accurate diagnosis. The patient advocacy group, Global Genes, reports that average time for a rare patient to receive an accurate diagnosis is 4.8 years (1). It is common for patients to be evaluated by numerous physicians – 8 or more is not unusual – and receive 2 to 3 misdiagnoses. And since every diagnosis is usually to believed to be the ”right answer” at the time, it leads to a false belief that healthcare professionals, the patient, and caregivers finally know what the issue is, and how they can begin to address it (4).
The process takes so long and is so well in known in the rare disease world that it has its own name: “The Diagnostic Odyssey”. The word “odyssey” has a special meaning for those in the rare disease community, because of the many obstacles that patients and their caregivers face along the way. While each patient’s journey is unique, there are many similar obstacles: frequent physician visits, endless lab tests, multiple misdiagnoses, fights with insurance companies, long waits to see specialists, costly travel, endless online searching, financial pain, and numerous missed opportunities to receive potentially life-changing treatments. The diagnostic inefficiencies not only result in wrong, ineffective, and unnecessary treatments, but they also can push the patient beyond viable treatment windows, which results in significant morbidity and, potentially, premature death (6).
What makes The Diagnostic Odyssey even more painful is that about two-thirds of rare disease patients are children (5). Families and kids travel all over the USA and the world seeking answers, and looking to connect to specialists that can give them more clues about what’s wrong with their child. During the odyssey, the patient may deteriorate, suffer multiple new symptoms, and often experience severe mental health issues. Patients also face long waits due to a shortage of medial geneticists and genetic counselors.
“It feels incredibly isolating to want to help your child and not be able to because even the doctors don’t know what’s wrong. To not have someone who understands because there is nobody like your child. To not be able to have a treatment plan because there is no diagnosis.”
—Susie Stretton
In The Mighty
December 15, 2015
And if they are fortunate enough to receive an accurate diagnosis, the care of children with rare diseases usually requires numerous visits to specialists in multiple locations. And most conditions may only have a handful of experts or specialty centers able to manage the disease. So the current wait to see specialists in academic centers is often 6-12 months.
The diagnostic odyssey creates an immense strain and psychological distress on the patients and their families. Patients see multiple providers, often outside of a their insurance network and geographic region, and their diagnosis is likely to be hampered by limited diagnostic tools, multiple wrong diagnoses, and false hopes. Numerous barriers stand in the way of shortening the diagnostic odyssey, including low disease awareness, access to the right specialists, insurance coverage limits, specialist shortages, and geographic barriers. The rare disease diagnostic odyssey is a hidden tragedy that affects a large – and mostly vulnerable – part of society. But unlike other large challenges that impact healthcare in the US, many of the solutions are relatively straightforward.
The Economic Impact of Rare Diseases
The most commonly cited disease estimates that the burden of a rare diseases is massive – at least $1 trillion/year in direct and indirect costs in the United States (7). A study published o=in 2022 estimated significantly higher costs – more than $2.2 trillion. This study also compared rare disease costs with “mass-market” chronic disease, and estimated that the average cost per patient to the healthcare system is approximately 10x the cost associated with “mass market” diseases (8.)
The direct costs start with long and frustrating diagnostic journey. Because patients with rare diseases so often go undiagnosed for long periods of time and are often misdiagnosed, they are intense users of the healthcare system. As patients go from doctor to doctor, with additional tests ordered at each appointment, the costs continue to add up. As noted earlier patients may see eight or more different physicians – most several times, each with their own set of lab tests, and then often experience multiple x-rays, CT scans, MRIs, and other imaging methods covering different parts of the body. In some cases, biopsies are performed.
Once accurately diagnosed, managing rare diseases is extremely expensive. Patients with rare diseases require specialized care from healthcare providers with expertise in their specific condition. Care for rare diseases is usually intensive and expensive, and most patients require ongoing treatments and interventions. The burden of direct medical or health-care costs can reach millions of dollars annually for many rare diseases, with cost drivers that include outpatient visits, hospitalizations and emergency visits, medications, palliative care, extra dental and vision care, insurance cost and reimbursement, rehabilitation care, home health care, medical devices, social services, and the use of outside caregivers (6).
In addition to the direct costs of diagnosis and care, rare diseases often cause high indirect costs for caregivers and families. In most cases, caregivers have to dedicate a large proportion of their time to the management of family members with rare diseases, requiring that they miss a large number of work days or stop working completely. If the rare disease patient in an adult, there will almost certainly be a significant negative impact on productivity. Individuals with rare diseases may experience significant disability, leading to missed workdays, decreased productivity, and reduced earnings.
Overall, the economic burden of rare diseases in the United States is significant, affecting patients, their families, healthcare providers, employers, and society as a whole. The economic impact of lack of rare disease awareness, with resulting delays in diagnosis, numerous misdiagnoses, associated ineffective treatment, and innumerable other costs is huge – accounting for a significant portion of the $1 trillion+ impact of rare diseases in the United States. Importantly, better education about rare disease may actually reduce overall healthcare spending by eliminating unnecessary testing and treatment that patients receive before an accurate diagnosis is made.
Diagnosis: The Challenge for Healthcare Professionals
According to a 2019 survey by NORD, 50% of patients and caregivers attributed diagnostic delays to a lack of (HCP) disease awareness (10).
About 1 out of 10 patients in an average clinical practice will, at some point in their lives, have a rare disease. But the average physician hasn’t been trained to consider the possibility that many of their patients – who probably have many symptoms that are consistent with many common diseases – may have an unknown rare disease. In medical school and residency, physicians are rightly taught that they should first consider a common diagnosis, not a rare one. Consequently, although most physicians will have to diagnosis or manage patients with a rare disease at some point in their professional lives, many assume that they are unlikely to ever see a rare disease patient in their practice.
Unsurprisingly, knowledge of rare diseases by average US clinicians is not optimal. Low rare disease awareness and knowledge among HCPs is one of the most important reasons why many rare disease patients face late and numerous misdiagnoses. According to a 2019 survey by NORD, 50% of patients and caregivers attributed diagnostic delays to a lack of (HCP) disease awareness (10). A majority of physical that they need to know more more about rare disease. Research indicates that most physicians (>80% of specialists and >60% of PCPs) want to learn more about rare diseases (11).
But there are more than 7,500 identified rare diseases, and perhaps as many as 10,000. Genetic and phenotypic variability add to the incomplete knowledge of rare diseases, which complicates the process of diagnosis. No healthcare professional could be expected to have the knowledge level needed to consider and accurately diagnose every rare disease that has been identified.
Physicians may also not be aware of what tests to order for patients – and when. The rapid technological advancements in genomics, sequencing, and genetic testing in this field make it virtually impossible for the average clinician to stay up-to-date on the availability – and potential value – of genetic tests for hundreds of diseases. Even when clinicians consider the option of genetic testing, most will refer patients to a medical geneticist, a specialty that currently faces extremely high demand, with typical wait-times for appointments of more than 3 months, and another 2-3 months to receive test results.
Another dimension of the rare disease diagnostic challenge that is often overlooked is the frustration and emotional impact on healthcare professionals. Trained to identify and solve problems and empathetic to the suffering of patients and families, HCP are often as frustrated by the mysteries of rare diseases as patients and families. Diagnosing rare pediatric diseases can be especially difficult , complex, and fraught with sensitive emotional issues. The age of many patients, the uncertainty surrounding the diagnosis, the fear of disease progression, and the potential lack of treatments all can contribute to an extremely stressful environment for healthcare professionals.
“Nothing about rare diseases is simple — not the diagnosis, not the daily care, not the long term”
Elizabeth Grehl Breden
In The Mighty
December 15, 2015
How the Gap Can Be Closed
Rare disease patient identification is difficult for physicians and other healthcare professionals – symptoms often overlap with more common diagnoses, and most physicians will encounter relatively few patients with rare diseases in their entire career. Even if they suspect a rare disease, most physicians lack the time to thoroughly research the possibilities – and there may not a clear sense of what to do next – what tests to order, who and where to refer, or even what information to search for online.
The task, however, is not quite as daunting as it might appear at first. Although there are at least 7,500 identified rare diseases, 150 conditions account for approximately 80% of rare disease patients and another 200 – 300 diseases account for another 15-18% (12). So, providing improved education about the “most common” 400-500 rare diseases could make a significant impact on the diagnostic journey for a large majority of patients.
Moreover, it’s possible to focus rare disease educational initiatives to make them as relevant as possible to specific specialties. Although rare diseases often impact multiple organ systems, the effect of most diseases can be matched to specialties that are most likely to be involved in their diagnosis and management, and then the most relevant education can be provided by specialty. By following this logic, the number of rare diseases that most individual healthcare professionals would need to learn about becomes manageable. Broader rare disease education for the greater number of rare diseases that primary care physicians may see is somewhat more challenging, but still manageable.
Strategies that can help close the gap:
Start earlier: Medical students and residents should be provided with more intensive rare disease education. Optimally, this training should include case-based discussions, patient encounters and skill-building exercises.
Improve continuing medical education (CME): Although there are dozens of online CME courses for individual rare diseases, courses should be to increase designed general awareness and rare diseases vigilance.
Leverage the novelty of rare diseases: Take advantage of the interest that most healthcare professionals have about science by designing educational programs that leverage the inherent novelty of rare diseases to engage and intrigue participants.
Engagement: One of the things that intrigues medical professionals is the challenge of clinical diagnosis. By creating content that engages HCPs in solving unusual cases, they can be engaged and informed about rare diseases, especially those that may seem like more common conditions.
Online Resources: Online resources, such as webinars, podcasts, blogs, and e-learning modules, can be made to provide healthcare professionals with current information on rare diseases.
The challenge of improving rare disease knowledge by healthcare professionals is daunting – but critical. As more epidemiological data become available, it’s clear that the number of people that have rare diseases is great – with most estimates indicating that 1 out of 10 Americans probably have or will have a rare disease, and a majority have yet to be accurately diagnosed. The value of improving the knowledge level about rare diseases for healthcare professionals has enormous scientific, human, and economic value, and should be a high priority for society.
Conclusions
The rare disease knowledge gap refers to the lack of information and understanding about rare diseases among physicians, researchers, and the general public. Despite their “rarity”, rare diseases collectively affect tens of millions of people in the United States, and many of them are life-threatening or severely debilitating. However, because each rare disease affects only a small number of people, they often receive less attention and funding than more common diseases.
Estimates indicate that of the 30 million people in the United States that have – or will have – a rare disease, and only a small minority have been accurately diagnosed.
Doctors and other healthcare professionals have committed their lives to doing every that they can to improve the lives of their patients – and research indicates that they want do more to help rare disease patients. But training and education about rare diseases has rarely been a priority of the healthcare system, and historically, more common diseases have received the vast majority of attention and education. The world has changed, and more rare diseases are increasing being identified and diagnosed, but there is a large gap between the knowledge that exists in academic medicine and everyday clinical practice. Closing the gap can make a major contribution to improving the lives of millions.
The key missing elements are:
recognition of the possibility that some patients may actually have a rare disease
awareness and knowledge of the clues that can help uncover a rare disease diagnosis
education about the specific symptoms and clues that can lead to faster diagnosis
The rare disease knowledge gap highlights the need for increased awareness of rare diseases to improve outcomes for affected individuals and families. Improving education and training to clinicians at the primary, secondary, and tertiary care level is the first step to an accurate diagnosis. Despite the technological advancement and increased data sharing, the majority of rare disease patients still experience extensive diagnostic odysseys, and many remain undiagnosed and a large group of patients are misdiagnosed. Better outcomes are possible with a relatively small investment in rare disease education.
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