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 University of Sheffield, School of Health and Related Research [ScHARR]. (See the "Availability of Companion Documents" field.)
Clinical Effectiveness
Search Strategy
The search aimed to identify all literature relating to the clinical and cost effectiveness of irinotecan, oxaliplatin and raltitrexed (Appendix 3 of the Assessment Report [see "Availability of Companion Documents" field]). The main searches were conducted in June, July and August 2004. No language, study/publication, or date restrictions were applied to the main searches. Searches were performed in Medline, Excerpta Medica Database (EMBASE), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CCTR), Database of Abstracts of Reviews of Effects (DARE), Science Citation Index, Office of Health Economics–Health Economic Evaluations Database (OHE HEED), National Health Service–Economic Evaluation Database (NHS EED), NHS Health Technology Assessment Database (NHS HTA) and Cumulative Index of Nursing and Allied Health Literature (CINAHL).
Inclusion and Exclusion Criteria
Phase III randomised controlled trials were included if they compared any of the proposed indications with existing recommended indications (Section 2.3 of the Assessment Report [see "Availability of Companion Documents" field]). Primary outcomes were identified as overall survival and progression-free survival. Secondary outcomes were identified as health-related quality-of-life, response rate and adverse events. Studies were excluded if they did not report either of the primary outcomes. Use of data from phase II studies and from non-randomised studies was only considered where there was insufficient evidence from good quality phase III trials, the former being studies appropriately powered to assess efficacy outcomes, rather than those directly associated with clinical effectiveness, and both being subject to selection bias. Reports of any studies not available in English as the time scale of the review precluded time for translation.
Trials were included if they recruited participants with advanced colorectal cancer, as defined in Section 2.1.4 of the Assessment Report (see "Availability of Companion Documents" field).
Only trials which compared 5-fluorouracil (5-FU) (with or without folinic acid), irinotecan oxaliplatin or raltitrexed in licensed combinations were included in this study. Where the extent of the treatment effect was confounded by the presence of active agents from other pharmaceutical classes, the trial was excluded.
Only trials which reported at least one of the primary outcomes, overall survival (OS) and progression-free survival (PFS) were included. OS was defined as the interval from randomisation to death from any cause. PFS was defined as the interval from randomisation to first evidence of disease progression or death from any cause. Secondary outcomes, response rates, toxicities and quality of life, were recorded where reported. Response rates were defined as the number of patients in each regimen achieving a partial or complete response, however defined. Toxicities and quality of life were abstracted as reported, however defined.
This review also includes all included studies in the original assessment report which meet the current inclusion criteria. A flow chart describing the process of identifying relevant literature can be found in Appendix 4 of the Assessment Report (see "Availability of Companion Documents" field) and a table summarizing the reasons for excluding those trials included in the previous review and the industrial submissions can be found in Appendix 5 of the Assessment Report (see "Availability of Companion Documents" field).
Cost Effectiveness
Identification of Economic Studies
Systematic literature searches were undertaken to identify all relevant studies relating to the economics of irinotecan, oxaliplatin and raltitrexed in the treatment of advanced colorectal cancer as compared with established 5-fluorouracil/folinic acid (5-FU/FA) containing regimens and best-supportive care. Details of the search strategies are reported above under "Clinical Effectiveness – Search Strategies". Hand-searching of retrieved articles and industrial submissions to NICE was also undertaken.
Inclusion/Exclusion Criteria
Studies which aimed to evaluate the cost-effectiveness of oxaliplatin, irinotecan or raltitrexed compared to established 5-FU/FA were included in the review. Economic studies were only included in the review if a full economic evaluation was reported, that is, those studies in which both the costs and benefits of chemotherapy were estimated. Partial evaluations in which either costs or benefits were estimated in isolation, and reviews of existing economic studies were excluded from the review of cost-effectiveness presented here. In addition, studies in which the methods of analysis were unclear were excluded from the review. All included studies were appraised using the checklist for assessing the quality of economic evaluations as proposed by Drummond and colleagues.