The clinical effectiveness and cost-effectiveness of primary stroke prevention in children with sickle cell disease: a systematic review and economic evaluation
Health Technology Assessment. 2012;16((43):):1-129.
BACKGROUND Sickle cell disease (SCD) is a recessive genetic blood disorder, caused by a mutation in the -globin gene. For children with SCD, the risk of stroke is estimated to be up to 250 times higher than in the general childhood population. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique which measures local blood velocity in the proximal portions of large intracranial arteries. Screening with TCD ultrasonography identifies individuals with high cerebral blood velocity; these children are at the highest risk of stroke. A number of primary stroke prevention strategies are currently used in clinical practice in the UK including blood transfusion, treatment with hydroxycarbamide and bone marrow transplantation (BMT). No reviews have yet assessed the clinical effectiveness and cost effectiveness of primary stroke prevention strategies in children with SCD identified to be at high risk of stroke using TCD ultrasonography. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of primary stroke prevention treatments for children with SCD who are identified (using TCD ultrasonography) to be at high risk of stroke. DATA SOURCES Electronic databases were searched from inception up to May 2011, including the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), EMBASE, the Health Technology Assessment (HTA) database, ISI Web of Science Proceedings, ISI Web of Science Citation Index, the NHS Economic Evaluation Database (NHS EED) and MEDLINE. REVIEW METHODS The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. A de novo Markov model was developed to determine the cost-effectiveness of TCD ultrasonography and blood transfusion, where clinically appropriate, in patients with SCD. RESULTS Two randomised controlled trials met the inclusion criteria involving a study population of 209 participants. One compared blood transfusion with standard care for children who are identified as being at high risk of stroke using TCD ultrasonography. In this trial, one patient in the transfusion group had a stroke (1/63) compared with 11 children in the standard care group (11/67). The other trial assessed the impact of halting chronic transfusion in patients with SCD. Sixteen patients in the transfusion-halted group had an event (16/41) (two patients experienced stroke and 14 reverted to abnormal TCD velocity); there were no events in the continued-transfusion group (0/38). No meta-analyses of these trials were undertaken. No relevant economic evaluations were identified for inclusion in the review. The de novo modelling suggests that blood transfusions plus TCD scans (compared with just TCD scans) for patients with SCD at high risk of stroke, aged >= 2 years, may be good value for money. The intervention has an incremental cost-effectiveness ratio of 24,075 per quality-adjusted life-year gained, and helps avoid 68 strokes over the lifetime of a population of 1000 patients. The intervention costs an additional 13,751 per patient and generates 0.6 extra years of life in full health per patient. The data available for the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusion of the model is reliable but further research is required to validate these findings. LIMITATIONS The main limitations relate to the availability of published clinical data; no completed randomised controlled trials were identified which evaluated the efficacy of either BMT or hydroxycarbamide for primary stroke prevention. Both the clinical and cost data available for use in the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusions of the model are reliable, but further research is required to validate these findings. CONCLUSIONS The use of TC
Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery
Transfusion Medicine. 2005;15((3):):209-17.
Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.