Association between haemoglobin levels and clinical outcomes and healthcare resource use in patients with sickle cell disease in England

Date of Approval
Application Number
Technical Summary

With current advancements in drug research, there is hope that Sickle cell disease (SCD) can be managed by a once daily oral direct-acting haemoglobin modifier for chronic, prophylactic treatment of patients which would in turn reduce the morbidity, mortality and health care costs associated with them. However, there is limited understanding of the most at-risk patients which would affect the impact of targeted treatments if they are to be made available on the NHS. There is also a limited availability of knowledge on the risk of adverse clinical outcomes such as stroke in this group.
This study aims to ascertain the association between haemoglobin (Hb) levels and selected clinical outcomes and healthcare resource use in patients diagnosed with SCD. This will be done by creating a cohort of patients with SCD using an algorithm based on codes. Further sub cohorts will be created out of the main cohort based on Hb levels, genotype, age and medications prescribed.
We shall describe demographic characteristics, occurrence of clinical outcomes including stroke and mortality. Health care resource usage will also be calculated and reported for primary care, inpatient, outpatient and A&E activity including cost. Outcomes will be described as total, means, medians, percentage or rates as appropriate.
In the comparative analysis, we shall look to null hypothesise that there is no relationship between risk of adverse clinical outcomes and SCD. Among patients with and controls without SCD, unadjusted and adjusted odds, odds ratios and mean incidence along with 95% confidence intervals will be calculated for all selected clinical outcomes and death at 1-6 months, >6-12 months and >12 months on comparing each cohort to matched controls. We shall match on age and sex and adjust for any other risk factors that we may identify as having an effect on the dependent variables.

Health Outcomes to be Measured

Prevalence of SCD; haemoglobin levels; Demographics (Mean and median age on inclusion, age distribution by decade, sex distribution, deprivation, Charlson co-morbidity score distribution, mean and median follow-up, total and mean admitted time, smoking status, BMI, alcohol consumption), prevalence of VOCs, ACS, Hypertension, Asthma, Stroke, History of leg ulcer, Diabetes, Upper respiratory tract infections, Osteonecrosis, Transfusions in the year prior to index, Gallstones, Chronic pain, Neoplasms benign and malignant, CKD by stage, Sepsis); crude death rate in the cohort; Healthcare resource outcomes (prescriptions issued in primary care, GP appointments in primary care, number of inpatient admissions, inpatient length of stay, inpatient HRG tariffs, number of outpatient appointments, inpatient HRG tariffs, number of A&E attendance, A&E HRG tariffs ); Clinical outcomes (Stroke, PH, CKD, ESRD, Leg ulcer, Composite ACS/pneumonia, mortality)


Jay Were - Chief Investigator - Health iQ
Jay Were - Corresponding Applicant - Health iQ
Archie Farrer - Collaborator - Health iQ
Boglarka Kovacs - Collaborator - Health iQ
Gulsah Akin Unal - Collaborator - Health iQ
Judith Ruzangi - Collaborator - Health iQ
Mico Hamlyn - Collaborator - Health iQ
Shea O'Connell - Collaborator - Health iQ


HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation