Rare Disease Nonadherence: A Global Problem


Globally, medication nonadherence is a costly yet underreported concern that negatively impacts patient outcomes and wastes precious resources, especially when it comes to rare diseases. 

Overall, the World Health Organization calls medication nonadherence a "worldwide problem of striking magnitude [1]." Since medication nonadherence cuts across patient populations and treatment types and extends beyond geographic, ethnic, and cultural boundaries, medication nonadherence profoundly impacts global health. 

The crisis deepens when you consider rare diseases. Already the discovery and production of medications and treatments requires considerable investment/cost – with cost of treatment often a barrier to access for some countries and ultimately patients which can lead to worse prognoses. But that gulf in healthcare outcomes is further exacerbated by nonadherence. Complex drug protocols, access to specialized care and side effects all contribute to rare disease patients' poor adherence to treatment.  

Even more alarming is the disproportionate impact of this nonadherence on African Americans and Latinos [2]. Notwithstanding access issues, the gulf in healthcare outcomes is further exacerbated by nonadherence due to factors such as socio-economic barriers, lack of trust in the healthcare system and systemic healthcare disparities. Medication nonadherence in such instances can lead to direct, often severe, consequences on patient outcomes, further escalating the already existing health inequities. 

Estimating the Global Impact of Nonadherence

Rare disease nonadherence is not a problem restricted to one or two diseases or geographic locales. Instead, it is a universal issue affecting all rare diseases and populations worldwide. Global statistics reveal a grim picture: an estimated 275,000 patients die yearly due to medication non-adherence [3]; a significant portion of these tragedies, approximately 125,000, occur in the US [4]. 

These figures are not mere statistics – they represent a colossal loss of life and a substantial economic toll. In the US alone, medication nonadherence to prescribed treatment is thought to cause at least 100,000 preventable deaths and a mammoth $100 billion in avoidable medical costs annually [5]. When adjusted for disease-specific costs of nonadherence per person, the economic burden can range from $949 to $44,190 (in 2015 US$) [6], representing a massive drain on healthcare resources. 

Furthermore, a 2021 study published in the Orphanet Journal of Rare Diseases examined data from a mix of commercial and public insurance payors over a nearly 15-year time span (2006–2020). The study found that per patient per year (PPPY) costs ranged from $8,812 to $140,044 for rare disease patients, significantly higher than the $5862 average for the control group [7]. Among the most expensive diseases were Urea Cycle Disorders (UCD), Lennox-Gastaut Syndrome (LGS), and Behcet's Syndrome (BD). 

The global impact of rare disease medication nonadherence is a multi-faceted problem that has substantial implications for patient outcomes, healthcare systems, and economies. As we move forward, it becomes increasingly crucial to address this pervasive issue and work toward effective solutions. 

Ethnic Minorities Disproportionately Affected by Rare Diseases 

Regrettably, certain communities face a steeper uphill battle against rare diseases than others. Approximately 80% of rare diseases are genetic [8], meaning they can run in families.  

Studies have repeatedly shown that ethnic minority groups, especially African Americans and Latinos, experience higher barriers to care for both rare and chronic diseases. This challenge, among others, contributes to higher death rates among these groups. According to the Black Women's Health Imperative, African Americans have higher death rates than whites for 12 of the 15 leading causes of death in the US, many of which are rare diseases [9]. 

Additional Challenges Experienced by Ethnic Minority Groups 

Rare disease communities that are underserved currently face significant barriers to care. Systemic, linguistic, and socio-economic challenges disproportionately affecting these diverse communities have been identified [10]. 

  1. Hospital Access Inequalities: Recognizing health equity issues that underserved communities face allows organizations and patients to actively challenge and rectify the roots of discrimination and disenfranchisement. The 2011 CDC Health Disparities and Inequalities Report [11] highlighted these issues, revealing that between 2004-2007, higher rates of preventable hospitalizations occurred among non-Hispanic blacks and Hispanics than non-Hispanic whites. 
  1. Obstacles in Accessing Treatment: Many barriers exist that hinder underserved communities from having equitable access to vital medications or procedures. For example, within the Black community where Sickle Cell disease is prevalent, biases can undermine their expression of pain, thereby affecting their access to appropriate pain relief [12]. 
  1. Inherent Health Risks in the Community: Numerous underserved communities dealing with rare diseases are also contending with inherent health risks and prevalent comorbidities. An increased risk of kidney failure in Black and Hispanic communities, for instance, can further complicate the diagnostic process and add to the complexities of managing rare diseases [13]. Plus, minority populations, regardless of whether they have rare diseases, exhibit higher rates of comorbidities such as hypertension, diabetes, obesity, and heart disease [14]. When these conditions converge with disparities in healthcare access, they can significantly exacerbate health outcomes for underserved rare disease patients. 

Final Thoughts

As a strategic partner to global pharmaceutical, life science, and rare disease companies, Atlantis Health recognizes the profound impact associated with rare disease treatment nonadherence. Supporting patients and their families to adhere to treatments as prescribe is crucial in improving the lives of those living with rare diseases. 

Medication nonadherence is a significant issue with a global impact. Through our research, we have highlighted the depth and breadth of this problem, especially in ethnic minority communities, and underscored the urgency to act. 

We hope our new Rare Disease Nonadherence Report is a valuable resource for stakeholders committed to supporting and treating people with rare diseases. By shedding light on the complex realities of medication nonadherence, we can collectively work towards innovative solutions that improve patient outcomes and reduce healthcare costs globally. 

Through shared understanding and action, we can make a significant difference in the lives of those living with rare diseases. Let's join forces to turn these insights into actions.  

You can read and access our new Rare Disease Nonadherence Report below. 


Access the report here



  1. World Health Organization. Adherence to long-term therapies: evidence for action. World Health Organization; 2003. 
  2. Lanouette, N. M., Folsom, D. P., Sciolla, A., & Jeste, D. V. Psychotropic medication nonadherence among United States Latinos: a comprehensive literature review. Psychiatric Services. 2019; 60(2): 157-174. 
  3. Watanabe, J. H., McInnis, T., & Hirsch, J. D. Cost of prescription drug–related morbidity and mortality. Annals of Pharmacotherapy. 2018; 52(9): 829-837. 
  4. Bosworth, H. B., Granger, B. B., Mendys, P., Brindis, R., Burkholder, R., Czajkowski, S. M., ... & Granger, C. B. (2011). Medication adherence: a call for action. American Heart Journal. 2011; 162(3): 412-424. 
  5. Kleinsinger, F. The unmet challenge of medication nonadherence. The Permanente Journal. 2018; 22. 
  6. Cutler, R. L., Fernandez-Llimos, F., Frommer, M., Benrimoj, C., & Garcia-Cardenas, V. Economic impact of medication non-adherence by disease groups: a systematic review. BMJ Open. 2018; 8(1): e016982. 
  7. 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. 
  8. Batshaw, M. L., Groft, S. C., & Krischer, J. P. Research into rare diseases of childhood. JAMA. 2014; 311(17): 1729-1730. 
  9. Blount, L. G. Diversity Elusive in Rare Disease Research. National Press Foundation. September 14, 2021. Accessed June 12, 2023. https://nationalpress.org/topic/diversity-elusive-in-rare-disease-research/.  
  10. Every Life Foundation. Challenges to Diversity in Rare Diseases. n.d. Accessed on Jun 12, 2023. https://everylifefoundation.org/rare-advocates/rare-diversity-hub/disparities-in-public-health/.  
  11. Center for Disease Control and Prevention (CDC). CDC Health Disparities and Inequalities Report – United States, 2011. CDC, US Department of Health and Human Services. 2011; 60.   
  12. Meghani, S. H., Byun, E., & Gallagher, R. M. Time to take stock: a meta-analysis and systematic review of analgesic treatment disparities for pain in the United States. Pain Medicine. 2012; 13(2): 150-174.  
  13. U.S. Renal Data System. USRDS 2016 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; 2016. 
  14. Graham, G. Disparities in cardiovascular disease risk in the United States. Current Cardiology Reviews. 2015; 11(3): 238-245.