There is a significant need for a wide range of clinical trials in the area of thalassemia and its related complications; however, the small U.S. thalassemia patient population (n < 1,500) limits trial enrollment and may deter investigators from initiating a U.S. based trial. Results from a survey conducted by the website for the Center for Information and Study on Clinical Research Participation (CISCRP) found that among people who suffer from severe chronic illness, only 6% participate in clinical trials. 1 Recognizing the problems of clinical trial recruitment in general and within the Thalassemia Clinical Research Network in particular, we sought insights from our patient population regarding trials that depend upon the participation of individuals with thalassemia.Although once considered a pediatric disorder, advances in treatment have resulted in an increase in life expectancy for people born with thalassemia. As a result, many patients now live into their 30's and 40's and beyond, and the widespread adoption of chelation therapy and the advent of more recent, easier-to-administer chelation therapies may mean that life expectancy will increase even more. As the number of adult thalassemia patients increases, more patients are potentially available to participate in clinical trials; however, as adults, these patients have greater constraints placed upon the time they have available for trial participation in addition to limited eligibility due to secondary complications.Moreover, changing immigration patterns create changes in the make-up of the thalassemia community. Recent decades have seen a greater influx of individuals from south Asia, southeast Asia, and China; many of the thalassemia patients from these communities have the ␣-thalassemia, rather than ␤-thalassemia variants.Geographic factors also impact the thalassemia community. The Cooley's Anemia Foundation estimates that about half of U.S. patients are seen at a major thalassemia treatment center, and that about half are not. It is assumed that geographic inaccessibility is a major factor for many of those who are not affiliated with a major treatment center.

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.

BackgroundMost patients with rare diseases have no effective treatment or cure available to them. However, scarcity of data and disease complexity mean the full extent of the patient, family and social burden of rare diseases remains undocumented. Understanding the cost drivers and the economic impact that a lack of treatment poses is critical for highlighting the unmet need to inform future investments and policymaking.MethodsWe selected five priority therapeutic areas (TAs; metabolic, neurological, congenital, hematological and immunological) encompassing 227 well documented rare diseases. Discussions with patients and physicians identified the 24 most relevant (highest unmet need) diseases within the five TAs. We assessed direct (costs associated with medical care), indirect (costs related to productivity losses) and mortality (costs associated with loss of life) costs. We also assessed these costs for 24 chronic mass-market (MM) diseases. Based on the overall cost burden per patient per year (PPPY) for the rare diseases, a scenario analysis was conducted to assess the average cost if treatments were not available. Lastly, the findings from the initial 24 rare diseases were extrapolated to 227 rare diseases in the five TAs. ResultsThe average cost burden of the 24 diseases analyzed ranged from $121 000 to $334 000 PPPY compared with $26 000 PPPY for MM diseases. Averaging across selected rare diseases, lack of treatment was associated with a 21.2% increase in total costs, from $198 000 to $240 000 PPPY. When these results were extrapolated to 227 rare diseases belonging to the five TAs, similar results were obtained: the average cost of rare diseases was approximately 10 times higher ($266 000 PPPY vs $26 000 PPPY) than for the MM diseases. ConclusionsOur findings demonstrate that rare diseases impose substantial economic burden, which remains high even when treatments are available. However, the cost composition shifts towards medical care and away from other types of burden. To the extent that new treatments provide clinical benefit for patients and their families, these shifts in burden are likely productive. Accelerated progress in the development of diagnostic methods, treatments and updated regulatory frameworks for rare diseases are recommended.