2/28/2025
The topics discussed in this post are current as of the date above. PHC4 will not be updating this page.
What Do I Need to Know?
Rare Disease Definition: a disease, disorder, illness, or condition that affects fewer than 200,000 Americans.1
In 2023, the Pennsylvania Health Care Cost Containment Council (PHC4) assisted the Pennsylvania Rare Disease Advisory Council (PARDAC) in analyzing over 1,200 survey responses collected from the rare disease community and presenting their findings to members of the PA Legislature.
PARDAC’s Pennsylvania Rare Disease Needs Assessment Survey: The outlined goal was “to learn more about the needs of individuals, families and loved ones affected by rare diseases in the Commonwealth of Pennsylvania so that we can make recommendations to improve access to needed resources.” This survey was an Internet-based survey conducted from September 23, 2020, to December 31, 2023, with a relaunch in February 2022 due to COVID-19 challenges and grant funding needs. It was shared with members of the rare disease community via social media, email campaigns, various websites, and in providers’ offices. This data is limited by sampling bias from the methods of collection and represents a single point in time.
As the second installment in PHC4’s Current Events series, PHC4 analysts investigated what exactly it is that makes rare diseases so difficult to study. The following article contains brief information on the rare disease community as a whole and the results of the Pennsylvania Rare Disease Needs Assessment Survey followed by an examination of the common challenges in rare disease research.
Living with a Rare Disease
The rare disease community encompasses a significant and diverse population, with over 7,000 rare diseases collectively affecting 25 to 30 million individuals in the United States.² Most of these diseases are genetic in origin, and approximately 70% begin during childhood.¹ Despite their individual rarity, these conditions present considerable healthcare challenges due to delayed diagnoses, limited treatment options, and the scarcity of FDA-approved therapies, with only about 5% of rare diseases having approved treatments.² Patients often face substantial healthcare burdens, including prolonged diagnostic journeys requiring consultations with multiple specialists and numerous tests.¹
In Pennsylvania, challenges in rare disease care are compounded by policy gaps highlighted in the National Organization for Rare Disorders (NORD) State Report Card. The state received low grades in areas such as medical nutrition coverage and prescription drug out-of-pocket costs, ranking below neighboring states like New Jersey and New York in these categories. However, Pennsylvania excels in Medicaid financial eligibility, newborn screening, and step therapy.¹ Economic burdens also weigh heavily on the rare disease community; in 2019, rare diseases accounted for a $966 billion national burden, including $418 billion in medical costs, $437 billion in productivity losses, and $111 billion in uncovered expenses.³ Pennsylvania’s rural composition, with 48 of 67 counties classified as rural,⁴ further exacerbates access challenges, as patients often travel long distances for specialized care, increasing transportation and lodging costs while delaying diagnosis and treatment.¹ These challenges were corroborated by patients who responded to the PARDAC Pennsylvania Rare Disease Needs Assessment Survey, visualized below.
Global approaches emphasize the importance of coordinated policies, advanced technologies, and robust care networks. Evidence for these approaches comes from New York’s policy recommendations which have increased early diagnosis through mandated genetic newborn screenings,⁵ and telehealth expansions in states like New Jersey have improved specialist access for rural populations.¹ Internationally, France’s third National Plan for Rare Diseases focuses on reducing diagnostic delays, strengthening research through structured data sharing, and fostering innovative treatment approaches, offering a model for systemic improvements in rare disease care.⁶
Interactive Visualizations of the Pennsylvania Rare Disease Needs Assessment Survey
Why is Analyzing Rare Diseases So Challenging?
Accurate Identification of Rare Disease Patients within Data
International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Definition: A standardized system used by healthcare professionals in the United States to code medical conditions and diseases.
To identify certain conditions to study within hospital discharge records, researchers use ICD-10-CM codes. To obtain a list of ICD-10-CM codes relevant to rare diseases, PHC4 analysts referenced nomenclature files from a rare disease registry, Orphanet. However, the codes in these files are not enough alone to identify all rare disease hospitalizations. Rare disease research is limited by the lack of available ICD-10-CM codes connected to a rare disease. When an ICD-10-CM code does exist, it can often be used to code for patients hospitalized with the common form of the disease as well as the rare form. This mixing of patients in the data is challenging to separate out later, during analysis.
The visualization below shows that 240 new rare diseases were identified and assigned an ORPHAcode between 2021 and 2024, but only 18 new ICD-10-CM codes appeared in the Orphanet nomenclature files. Additionally, non-specific codes, like Q87.8 – Other specified congenital malformation syndromes, can be linked to as many as 531 unique rare diseases.
Misdiagnoses and inaccurate coding further complicate the challenges of identifying rare disease patients. By definition, these diseases are uncommon, and health care providers are not trained in their identification or treatment. The lack of familiarity with rare diseases can lead to misdiagnoses and inaccurate ICD-10-CM codes being recorded in the hospitalization discharge record.
Overestimating or Underestimating?
When uncertainty exists in calculations, a common practice is to discuss whether the calculated values may be overestimates or underestimates, the reasoning behind the conclusion, and by approximately how much the over- or underestimate is. The challenges of accurately identifying rare disease patients complicate this common practice.
As an example, imagine a researcher trying to identify the number of people who were hospitalized for a certain rare disease each year. The following two approaches show how researchers can overestimate or underestimate.
Overestimate – The researcher is studying a disease or group of diseases with an ICD-10-CM code that also has common disease variants. The researcher is unable to separate rare disease patients from the rest of the group and overcounts the number of people, because patients with the common form of the disease are included in the count. Knowing the rate at which the rare variant occurs compared to the common variant helps researchers calculate how much of an overestimate their calculation is likely to be. However, this information is not always available.
Underestimate – The researcher is studying ICD-10-CM codes that are specific to a single rare disease which is known to be often misdiagnosed. The researcher is unable to identify all of the rare disease patients hospitalized that year because of misdiagnoses and inaccurate ICD-10-CM codes and therefore, undercounts the number of people. Knowing the rate of misdiagnosis helps researchers calculate how much of an underestimate their calculation is likely to be. However, this information is not always available.
Challenges of Low Patient Volumes
The Centers for Medicare & Medicaid Services (CMS) instructs researchers, working with CMS data, to not report, or to suppress, any values in their data that are equal to 10 or less. By only reporting on values above 10, researchers protect the confidentiality of patient information by avoiding the release of information that can be used to identify individuals.7
The visualization below shows three different maps that display the differences in the extent of required data suppression according to the CMS policy. Researchers visualizing hospitalizations at a county-level require no suppression because each county had more than 10 hospitalizations. Researchers studying at a zip code-level require some suppression because not all zip codes had more than 10 hospitalizations. Finally, researchers studying a single ICD-10-CM code at a zip code-level require more suppression because fewer zip codes had more than 10 hospitalizations than the previous map.
Conclusion
Research and analysis of rare diseases both as a collective population and by individual disease is challenged by the current ICD-10-CM coding system, misdiagnoses and inaccurate code assignment, and low patient volumes which require some level of data suppression to protect patient confidentiality.
If you enjoyed this article and are interested in learning more about the data and services PHC4 has to offer, let us know by filling out the survey below. Additionally, check out the first Current Events article from PHC4, Non-Compete Agreements in Health Care.
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Additional Resources
For Patients and Caregivers:
- Pennsylvania Rare Disease Advisory Council (PARDAC) – pardac.org
- State-specific resources, policy updates, and support networks
- National Organization for Rare Disorders (NORD) – rarediseases.org
- Provides patient support, advocacy, and a rare disease database
- Genetic and Rare Diseases (GARD) Information Center – rarediseases.info.nih.gov
- Reliable information on rare diseases from the NIH
- Global Genes – globalgenes.org
- Community-building and support for rare disease patients and families
For Advocates:
- EveryLife Foundation for Rare Diseases – everylifefoundation.org
- Promotes policy changes and legislative advocacy
- Rare Action Network (NORD) – rareaction.org
- State-based advocacy initiatives and resources
- Disability Rights Pennsylvania – disabilityrightspa.org
- Legal advocacy for individuals with disabilities, including rare diseases
- Pennsylvania Health Law Project (PHLP) – phlp.org
- Provides free legal services to Pennsylvanians facing healthcare access issues
For Researchers:
- PHC4 Data Requests – https://www.phc4.org/request-custom-data/
- Orphanet – orpha.net
- Rare disease registry, clinical trials, and research resources
- Rare Diseases Clinical Research Network (RDCRN) – rarediseasesnetwork.org
- NIH-funded research consortia on rare diseases
- NIH Genetic and Rare Diseases Research – ncats.nih.gov
- Resources for researchers, including funding opportunities and databases
References:
- National Organization for Rare Disorders. Rare disease facts and statistics. 2023. https://rarediseases.org
- National Institutes of Health. Rare diseases FAQ. 2022. https://rarediseases.info.nih.gov
- EveryLife Foundation for Rare Diseases. The national economic burden of rare diseases. 2021. https://everylifefoundation.org/burden-landing/
- Center for Rural Pennsylvania. Rural Pennsylvania’s 67 counties. 2020. https://center-for-rural-pennsylvania-data-hub-ruralpa.hub.arcgis.com/pages/county-profiles
- New York State Department of Health. New York State rare disease workgroup report. 2022. health.ny.gov/diseases/raredisease/
- Buzyn A, Vidal F. French national plan for rare diseases 2018-2022. 2022. https://www.eurordis.org/rare-disease-policy/national-policy/national-plan-for-rare-diseases-france/
- U.S. Department of Health & Human Services. CMS Cell Suppression Policy. 2020. https://www.hhs.gov/guidance/document/cms-cell-suppression-policy
