The Impact of Rare Disease Nonadherence on Health Outcomes


Three hundred million people globally struggle with rare diseases [1]. Measuring the impact of these conditions isn't solely about the monetary costs. From the emotional strain on family members to the social isolation and stigma, the consequences of rare diseases ripple outwards, despite being generally unseen by society at large. Such situations are often the best-case scenario, as, for many, nonadherence to treatments leads to worsening physical symptoms and greater pressure on an individual's support systems. 

While individually, each rare disease can comprise as few as a handful of patients, collectively, the over 7,000 rare diseases [2] form a sizable proportion of global medical costs. With few pharmaceutical interventions available, those that do exist often come with eye-watering price tags and a lengthy list of side effects.  

According to a recent pilot study, the already costly expenditure for rare diseases may have been underestimated by a factor of three or five [3]. That would make the cost of rare diseases on par with the costs for people living with more common chronic conditions such as cancer or heart failure. 

Worse, the cost per patient per year (PPPY) for rare diseases ranged from $8,812 to $140,044 compared to $5,862 for those without a rare disease [3], meaning nonadherence to rare disease treatments has an outsized impact on overall healthcare costs. Such diseases, therefore, should not be considered a trivial and marginal part of budgets; rather, rare disease nonadherence impacts are a critical, multi-faceted cause of lost expenditure. 

Rare Disease Nonadherence: An Overview

Based on the Atlantis Health 2014 Adherence Research Study as well as our ongoing experience with pharmaceutical clients who provide medication and support for people living with different types of rare diseases, we estimate that rare disease medication nonadherence rates can range between 58-65%.  

These medication nonadherence rates are very high and similar to what you see in the general population of people living with chronic diseases. This is not surprising since we know that medication nonadherence is a global problem and does not discriminate across diseases and treatments. 

Since rare disease nonadherence is just as likely to result in a reduction in quality of life & mortality as more common chronic diseases, it is important that we understand and address rare disease nonadherence as a patient care priority. 

Rare Disease Nonadherence Impacts and Adverse Outcomes

The ripple effect of rare disease nonadherence extends far beyond mortality rates, resulting in a variety of negative health outcomes. These outcomes manifest in distinct yet interrelated dimensions – physical, emotional, and social - each demanding a tailored approach to remediation and prevention.

Physical Impact of Nonadherence

Nonadherence to rare disease medications often leads to an alarming escalation in symptoms and a general decline in physical health. Without the mitigating effects of medication, these diseases can advance unchecked, accelerating physical deterioration and, in the most severe cases, contributing directly to premature death. 

Furthermore, nonadherence can also increase the risk of disease-related complications, further compromising the patient's health status. These complications, which often require additional medical interventions, compound the physical burden borne by patients and strain healthcare resources. 

Emotional Impact of Nonadherence

Coping with a rare disease necessitates continuous emotional adjustment. The disease's omnipresence forces patients to confront a persistent undercurrent of anxiety and uncertainty, which nonadherence only intensifies. 

Research by the National Library of Medicine shows a significant increase in the rates of depression and anxiety among nonadherent patients. [4] The emotional toll of nonadherence extends beyond the direct effects of the disease, encompassing the stress and anxiety associated with escalating symptoms and increased healthcare encounters.

Rare Disease Impact on Healthcare Systems

Given their chronic, progressive, and often life-altering nature, rare diseases pose a greater challenge to healthcare systems than more common diseases. Diagnoses often occur at a young age, and due to the seriousness of these conditions, patients require frequent and extended hospital stays, thereby escalating medical expenses over a lifetime. 

While quantifying the precise healthcare costs associated with rare disease nonadherence remains challenging, we can infer they're substantial. Data suggests nonadherence rates for rare diseases are at least comparable to those of more common diseases. Furthermore, rare disease patients are more likely to be hospitalized. In fact, medication nonadherence contributes to up to 25% of hospitalizations annually in the US [5]. 

Consider the stark comparison: patients with rare diseases experience longer average hospital stays (6.3 days) compared to those with more common conditions (3.8 days) and nearly double the average total charges per hospital discharge ($69,275 versus $36,718) [5]. 

Final Thoughts

Medication nonadherence has such a profound impact on health that the World Health Organization has stated that "increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments [6]."  

Rare disease medication nonadherence deserves a prominent place in our considerations of overall medication adherence. Recognizing this, Atlantis Health has conducted ground-breaking research to understand the underlying causes of rare disease treatment nonadherence worldwide. 

The health impacts associated with rare diseases are too significant to overlook. We hope our new research report on rare disease nonadherence will be widely disseminated and carefully considered by all key stakeholders committed to supporting and treating people living with rare diseases. 

Please read and access our new Rare Disease Nonadherence Report. 


Access the report here



  1. Nguengang Wakap, S., Lambert, D. M., Olry, A., Rodwell, C., Gueydan, C., Lanneau, V., ... & Rath, A. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. European Journal of Human Genetics. 2020;28(2): 165-173. 
  2. Food and Drug Administration (FDA). Rare Disease at FDA. Published December 13, 2022. Accessed on May 28, 2023.
  3. Tisdale, A., Cutillo, C. M., Nathan, R., Russo, P., Laraway, B., Haendel, M., ... & Pariser, A. R. The IDeaS initiative: pilot study to assess the impact of rare diseases on patients and healthcare systems. Orphanet Journal of Rare Diseases. 2021; 16: 1-18. 
  4. Uhlenbusch, N. (2019) Depression and anxiety in patients with different rare chronic diseases: A cross-sectional study, National Library of Medicine. Available at:
  5. Navarrete-Opazo, A. A., Singh, M., Tisdale, A., Cutillo, C. M., & Garrison, S. R. Can you hear us now? The impact of healthcare utilization by rare disease patients in the United States. Genetics in Medicine. 2021;23(11): 2194-2201. 
  6. Sabaté, E. Adherence to long-term therapies: evidence for action. World Health Organization; 2003.