Note from the National Guideline Clearinghouse (NGC): The National Institute for Health and Clinical Excellence (NICE) commissioned an independent academic centre to perform a systematic literature review on the technology considered in this appraisal and prepare an assessment report. The assessment report for this technology appraisal was prepared by the Peninsula Technology Assessment Group, University of Exeter and Wessex Institute for Health Research and Development, University of Southampton (see the "Availability of Companion Documents" field.)
Clinical Effectiveness
Search Strategy
Three separate searches of electronic databases were performed to identify published studies and ongoing research (see Appendix 10.3, page 90 of the Assessment Report [see the "Availability of Companion Documents" field]).
Imatinib
The search performed for the previous NICE assessment report on imatinib as second line treatment for chronic myeloid leukaemia (CML) was updated. The previous strategy identified studies assessing first line treatment of CML. The search was not restricted by study design.
Interferon (INF) Alpha versus Hydroxyurea (HU)
The Assessment Group updated the previous NICE assessment report search for the comparison of HU and IFN-alpha. This search was restricted to randomized comparisons, as high-level evidence is known to exist.
Interferon Alpha versus Bone Marrow Transplant (BMT)
The Assessment Group conducted searches to identify evidence for BMT versus IFN-alpha. No restrictions by date of publication were applied to this search.
All searches were restricted to English language and the search terms and strategy are outlined in Appendix 10.3 (page 90 of the Assessment Report [see the "Availability of Companion Documents" field]). Bibliographies of identified publications were searched for further relevant articles, handsearching of conference abstracts (European Haematology Association, American Society of Clinical Oncology, International Society for Experimental Hematology, and American Society for Hematology) for imatinib was performed, and the manufacturers of imatinib were approached for unpublished studies.
Inclusion and Exclusion Criteria
Two independent researchers reviewed titles and abstracts for inclusion. The full text of articles deemed relevant were obtained and the two researchers independently reviewed each for final inclusion. Disagreements were resolved by consensus.
The following inclusion criteria were applied:
Study Design
- Imatinib compared to any other treatment: studies with a control group only
- IFN-alpha compared to HU: randomised controlled trials only
- IFN-alpha compared to BMT: studies directly comparing IFN-alpha and BMT in the same study only
Stricter study design criteria were applied to comparison of IFN-alpha and HU due to the large number of randomised trials known to be available.
If studies were reported only in abstract form the Assessment Group tried to obtain the full text article. If a full text article was not available the abstract was excluded.
Population
Adults presenting for first line treatment of CML in chronic phase were included. Studies of patients in accelerated or blast phases were excluded.
Intervention and Comparisons
Studies comparing the following were included:
- Imatinib compared to any other treatment
- IFN-alpha compared to HU
- IFN-alpha compared to BMT
Studies of HU were only included if at least 75% of the control group received HU (e.g., at least 75% received HU and up to 25% received other agents such as busulphan [BU]). Relevant meta-analyses were only included if they reported all relevant outcomes that were present in the original reports of the randomised controlled trials (RCTs), otherwise the original RCTs were included.
Outcomes
Quality of life, overall survival, haematological response, cytogenetic response, and adverse effects were included.
Cost Effectiveness
Electronic databases were searched for published economic studies. The economic search performed for the previous NICE assessment report on imatinib as second line treatment for CML was updated. All economic studies of any treatment for chronic phase CML in adults have been included.