Feasibility and utility of a sickle cell disease registry for research and patient management

Abstract

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis aimed to evaluate the feasibility and utility of a sickle cell disease registry for clinical patient management and research. Five hospitals out of nine in the North West London health region participated in the registry, with 78 percent coverage of the sickle cell disease population. There was 80% case ascertainment in participating hospitals. Aggregated anonymised demographic and diagnostic data was collected for all haemoglobinopathy patients. This provided the core dataset for quantifying prevalence of sickle cell and thalassaemia and mapping local hospital workloads and service requirements. Thirteen percent of HbSS adult patients were taking hydroxycarbamide. The cohort of patients treated with hydroxycarbamide was evaluated. Sixty two of the 80 patients started on treatment were included. Follow-up was censored after 9 years, totalling 249 person-years of data with a median follow-up of three years (IQR, 1-6). Results showed that haematological benefits were maintained in the long-term with treatment, but evidence of long-term clinical effectiveness was less strong. This appeared to be due to the patterns of clinical management in everyday practice. Patients tend to be treated with modest doses of hydroxycarbamide due to intolerance or inability to attain or maintain maximum tolerated dose. For example maximum tolerated dose was the aim of treatment for 91% of patients but it was achieved for 65% of participants. Non- compliance with treatment and monitoring schedule was the main reason for non- attainment. Results suggest that it is sensible to strive for maximum tolerated dose to ensure therapy remains effective, but with more realistic expectations of the dose patients can attain and maintain. Doses in adult patients average 20mg/kg/day and 25mg/kg/day in children. Adult patients may be able to achieve a higher dose, if there was more stringent monitoring and improved management of non-compliance. The North West London HU Sub-Registry proved useful for measuring long-term effectiveness and tolerability of hydroxycarbamide. Routinely collected data was utilized for both clinical management and research purposes. The novelty lay in examination of the nuances of routine clinical practice. An electronic patient record was developed as a clinical management tool. It is the first study reporting long-term outcomes for UK sickle cell disease patients on hydroxycarbamide. Findings should help clinicians devise effective treatment protocols and strategies for managing patients commenced on this therapy. Interventions need to be targeted at increasing utilisation, patient adherence and persistence with treatment. The electronic patient record could be used to maximise treatment benefit and improve adherence. More effective involvement of the multidisciplinary team and primary care colleagues in patient education and management should improve usage. Patients and carers need up to date and easy to assimilate information to make informed decisions about treatment options. Maintaining a SCD registry is challenging. Models which operate as clinical information systems provide an incentive for participation. These enable active involvement of local care providers in registry management and the ability to keep and utilize their own data. Clinicians require accurate and current data for patient management and to enable them to benchmark their local outcomes against national outcomes and care standards