Hemoglobinopathies are among the most common inherited blood disorders worldwide and encompass different types of hemoglobin disorders, notably severe sickle cell disease (SCD) and transfusion dependent beta-thalassaemia (TDT). Both severe SCD and TDT interfere with the delivery of oxygen from the lungs throughout the body. Severe SCD is associated with pain crisis (also called vaso-occlusive crisis) which occurs when the sickle-shaped cells transporting the oxygen into the tissues have become stuck in the blood vessel in for example, the bones, chest, or penis area (also known as priapism). This event often requires emergency hospitalization. Other cardiovascular or bone and joint complications can also occur which require lifelong supportive care and intensive treatments. Similarly, TDT can result in lifelong complications such as anaemia, liver, cardiovascular, and endocrine complications. For these patients, regular blood transfusions are administered concomitantly with iron chelation drugs to lower risk of iron overload complications caused by the disease and the blood transfusions. SCD and TDT disease management include a range of resources such as visits to the doctor, hospital care, and prescription medications (for example pain medications). Hence, the overall aim is to determine the patients’ clinical characteristics, the mortality and the resource use associated with the costs in patients diagnosed with severe SCD and TDT at any age compared to the general population in England. This will provide crucial insights into how patients are managed in England, improve the understanding of current unmet need in severe SCD and TDT.
This is a retrospective cohort study evaluating the clinical and economic burden of patients with severe SCD and TDT at any age using primary care records (Clinical Practice Research Datalink (CPRD)) linked with secondary care data (Hospital Episode Statistics (HES)) in a real world setting in England. The study design includes two different populations: one with severe SCD, and the other with TDT. The severe SCD population will be defined as patients who have a diagnosis of SCD and two or more vaso-occlusive crises within a specific time period. Whereas, the TDT population will be defined as patients with a diagnosis of beta-thalassaemia and eight or more transfusion events within a specific time period in CPRD and/or HES. TDT and severe SCD patients will be independently matched exactly (1:5 ratio) to patients without the disease from the “general population” by age, sex, general practice, and ethnicity. Descriptive analyses of patient demographics (including patient level index of multiple deprivation (IMD)), clinical, and treatment characteristics will be performed in both cohorts as well as in the matched cohort using summary statistics. IMD data will be linked as a proxy for patient socio-economic status, which will be an important patient characteristic as it could be associated with severe SCD or TDT. During the follow-up, mortality rates, and health care resource utilization and associated costs will be determined and compared to the matched cohort using comparative analysis such as Z-test. Treatment use’s rates (prescriptions/procedures) will be reported in the severe SCD and TDT cohort, and complications’ rates in both cohorts and the matched cohort. Iron levels will be reported for each 1-year interval in both cohorts. This research will provide crucial insights into how patients are managed in England and improve the understanding of current unmet need in severe SCD and TDT.
The main outcomes of interest for this study are:
Iron levels in primary care; severe sickle cell disease (SCD) acute complications in primary and/or secondary care (gallstones, acute renal failure, cerebral vasculopathy, infections, post-hyphaemia glaucoma, retinal infarction, splenic infarction, stroke, transient ischaemic attack, vaso-occlusive crisis); severe SCD chronic complications in primary and/or secondary care (leukocytosis, bone and joint problems, cardiopulmonary complications, chronic leg ulcers, chronic pain, complications of pregnancy, delayed puberty, erectile dysfunction, functional asplenia, hepatobiliary complications, hyposplenism, hyposthenuria, infertility, liver complications, malignancies, mental health problems, myelodysplastic syndrome, neurocognitive impairment, proteinuria, renal complications, retinopathy/retinal disorders); transfusion dependent beta-thalassaemia (TDT) acute complications in primary and/or secondary care (cardiopulmonary complications, hypercoagulable state, infections); TDT chronic complications in primary and/or secondary care (cardiovascular complications, endocrine complications, bone disorders, liver complications, malignancies, mental health problems, myelodysplastic syndrome, renal complications, splenomegaly, urinary tract complications); medical prescriptions (hydroxycarbamide, iron chelation therapies, penicillin, folic acid, pain relieving medications); medical procedures (transfusions, splenectomy); health care resource utilization (HCRU) in primary care (general practice visits, nurse visits, prescriptions recorded in primary care); HCRU in secondary care (accident and emergency admissions, outpatient visits, inpatient hospitalizations, all non-transfusion admissions, all overnight admissions); and mortality.
Additional exploratory outcomes related to patients with hematopoietic stem cell transplant (HSCT): Graft versus host disease; bone marrow transplant rejection.
Sophia Fleming - Chief Investigator - IQVIA Ltd ( UK )
Nelly Ly - Corresponding Applicant - IQVIA Ltd ( UK )
Elena Chaparova - Collaborator - IQVIA Solution Bulgaria EOOD
Fiona Ingleby - Collaborator - IQVIA Ltd ( UK )
Nikolay Trankov - Collaborator - IQVIA Solution Bulgaria EOOD
Rachel Armstrong - Collaborator - IQVIA Ltd ( UK )
Sophia Fleming - Collaborator - IQVIA Ltd ( UK )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;Patient Level Index of Multiple Deprivation