A systematic review and economic evaluation were conducted to assess the clinical effectiveness of primary stroke prevention strategies for children with SCD who were identified by TCD ultrasonography to be at high risk of primary stroke. The systematic review was guided by the general principles recommended by the Centre for Reviews and Dissemination (CRD) for undertaking reviews in health care.67
In order to ensure that adequate clinical input was obtained, an advisory panel comprised of clinicians and experts in the field was established. The role of this panel was to comment on the draft report and answer specific clinical questions as the review progressed. In addition, a lay advisor was recruited to the panel to ensure that the review addressed patient issues.
Identification of evidence: clinical effectiveness
The search incorporated a number of strategies, combining index terms (for the disease) and free text words for the technologies involved. The search strategies had no language restrictions and did not include methodological filters that would limit results to a specific study design. Details of the search strategies and the number of records retrieved for each search are provided in Appendix 1. All references were exported to an EndNote version 5 (Thomson Reuters, CA, USA) bibliographic database.
The following electronic databases were searched (YD) for relevant published literature for the period 1950 to May 2011:
- CDSR (Cochrane Database of Systematic Reviews)
- CENTRAL (Cochrane Central Register of Controlled Trials)
- DARE (Database of Abstracts of Reviews of Effects)
- Health Technology Assessment database
- ISI Web of Science Proceedings (Index to Scientific & Technical Proceedings)
- ISI Web of Science Citation Index Expanded (SCIE)
- NHS EED (NHS Economic Evaluation Database).
Given the specialised nature of this disease, searches of conferences were not carried out; clinical advice suggested that the only published data would be found in the literature describing the existing clinical trials.
Selection of evidence
The records identified by the electronic searches were assessed for inclusion in two stages. Two reviewers (MGC and JG) independently scanned all titles and abstracts identified by the search to ascertain which articles may be relevant to the clinical review. Full-text versions of all records selected during the initial screening process were obtained to permit more detailed assessment. These were then assessed independently by two reviewers (MGC and JG), using the inclusion criteria shown in Table 8. The inclusion/exclusion assessment of each reviewer was recorded on a pre-tested, standardised form. Disagreements were resolved by discussion and, if necessary, another reviewer was consulted. A flow diagram summarising the selection and inclusion of studies is provided in Appendix 2, Figure 13.
Data extraction for the review of clinical effectiveness was carried out by two reviewers (MGC and JG). Data were abstracted by one reviewer and then checked for accuracy by a second reviewer. Data presented from multiple reports of single trials were extracted as a single record.
Two reviewers (MGC and JG) independently evaluated the included studies for methodological quality using criteria based on guidance published by CRD.67 Any discrepancies in quality grading were resolved through discussion.
Methods of data synthesis
Individual study data and quality assessment are summarised in structured tables and as a narrative description. The primary treatment outcome relevant to this review was incidence of stroke. The differences in patient groups between the included trials precluded a statistical synthesis.
Identification of evidence: cost-effectiveness
A comprehensive review of the literature was undertaken to identify all published economic evaluations of primary stroke prevention in children with SCD identified to be at high risk of stroke by TCD ultrasonography using the main search strategy outlined above (see Identification of evidence: clinical effectiveness, above).
Selection of evidence
During the clinical effectiveness screening, all papers that appeared to include economic data were identified. Full-text copies of these papers were subsequently obtained and two reviewers (MGC and JG) independently assessed them for inclusion, using the inclusion criteria described in Table 8. Any disagreements regarding inclusion of economic studies were resolved by discussion. No relevant economic evaluations were identified for inclusion in this review. A flow diagram summarising the selection and inclusion of studies is provided in Appendix 2, Figure 14.
NIHR Journals Library, Southampton (UK)
Cherry MG, Greenhalgh J, Osipenko L, et al. The Clinical Effectiveness and Cost-Effectiveness of Primary Stroke Prevention in Children with Sickle Cell Disease: A Systematic Review and Economic Evaluation. Southampton (UK): NIHR Journals Library; 2012 Nov. (Health Technology Assessment, No. 16.43.) 3, Methods.