Cost of Care of Rare Hematologic Disorders in the United States: Call to Action for Policy Supporting Pharmacologic Innovation
Authors: Andreu Perez Pedro , Cioffi Gina , Karam Jenny , Child Caroline , Tricta Fernando , Chiesi Giacomo 
Published: November 2021

Abstract
BACKGROUND: Rare diseases (RD) present a societal concern because of lack of treatment availability and difficulty developing new treatments. Even when treatment options exist, there are considerable barriers to diagnosis and access to specialty care.

OBJECTIVES: To estimate direct (attributable to patient care), indirect (patients' and caregivers' loss of productivity), and mortality-related costs of 5 rare hematologic disorders (atypical hemolytic uremic syndrome [aHUS], acute intermittent porphyria, acquired aplastic anemia, beta thalassemia major, and sickle cell disease) and evaluate burden of care, both when treatment is available and when no treatment exists. We compared these costs with mass market (MM) diseases, including a common hematologic disorder, deep vein thrombosis (DVT), to highlight the need to better serve RD individuals.
METHODS: We evaluated peer-reviewed published articles and databases (e.g., Orphanet, the Genetic and Rare Disease Information Center, NORD, NIH), conducted interviews with patient advocacy groups (e.g., Global Gene, the EveryLife Foundation for Rare Diseases, NORD) and key opinion leaders (e.g., Penn Blood Disorders Center), and referred to the US Bureau of Labor Statistics and Medi-Span Price Rx. We performed a statistical analysis to confirm that the sample size of patients covered in our disease selection was significant. In-depth analyses were performed to assess the per patient per year (PPPY) direct, indirect, and mortality costs associated with the 5 disorders, as well as costs for MM diseases, including DVT. While treatments exist for each of these 5 rare disorders, there are no universal curative options. Cost data for MM diseases, including DVT, were derived from literature reviews.

RESULTS: The economic burden of rare hematologic disorders in the US is considerable.
For most diseases, treatment costs account for the majority of total direct costs (52-90%). Indirect and mortality costs account for 4% and 22% of the total burden cost, respectively, but mortality costs vary widely (4-74% of total costs).
Highest overall direct cost observed was for aHUS ($530k) due to challenging diagnosis, persistent treatment, and poor prognosis. Productivity loss is 2 hours/week for patients and 2-4 hours/week for caregivers. The life expectancy of aHUS patients is ~60 years, but if untreated this may be shortened to ~35 years.
The lowest overall direct cost was for beta thalassemia major ($69k). The majority of direct costs are split between treatment costs and medical procedures. Patient productivity loss is estimated to be &gt;3.5 weeks of work loss/year in the 60% of patients who require bimonthly transfusions. Caregiver burden constitutes 9.2 hours/week of work loss. New therapies are likely to offset mortality costs in the future.
Although the direct, indirect, and mortality costs of these 5 disorders are high (average total cost $228k), the burden of cost is higher in all scenarios if treatments did not exist (60% increase in overall cost). As would be expected under the "no treatment" scenarios, the direct costs attributed to each disease decreased, but indirect and mortality costs increased.
Value of treatment is demonstrated by decreases in PPPY indirect costs. When no treatments were available, the range for productivity loss was ~$33k to $61k for patients and ~$25k to $61k for caregivers, compared with ~$3k to $22k for patients and ~$4k to $5k for caregivers when treatments were available.
The average PPPY costs of MM diseases for which treatments are available, including DVT, are estimated to be between $6k to $27k for direct costs, $10k to $16k for indirect costs, and $3k to $24k for mortality costs. In comparison with MM diseases, including DVT, the 5 rare disorders had average direct costs of ~$169k (a 6.25- to 26-fold increase), indirect costs of ~$9k (a modest decrease), and mortality costs of ~$50k (a 2.1- to 15-fold increase).
CONCLUSIONS: These scenario analyses demonstrate that RD therapies generate positive economic value. Further, analysis shows that RD pose a greater social economic burden than MM diseases. This information can be utilized to further efforts by the RD community for increased governmental investment in RD treatment, diagnosis, and access.

Disclosures
Andreu Perez: Chiesi Global Rare Diseases: Other: PA is a full-time employee IQVIA. The employer of PA received consulting fees from Chiesi Global Rare Diseases for this analysis. Cioffi: Chiesi Global Rare Diseases: Current Employment. Karam: Chiesi Global Rare Diseases: Other: JK is a full-time employee IQVIA. The employer of JK received consulting fees from Chiesi Global Rare Diseases for this analysis. Child: Chiesi Global Rare Diseases: Other: CC is a full-time employee IQVIA. The employer of CC received consulting fees from Chiesi Global Rare Diseases for this analysis. Tricta: Chiesi Canada Corp: Current Employment. Chiesi: Chiesi Farmaceutici SpA: Current Employment.