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 Evidence Review Group (ERG) report. The ERG report for this technology appraisal was prepared by the Liverpool Reviews and Implementation Group, University of Liverpool (see the "Availability of Companion Documents" field).
Clinical Effectiveness
Search Strategy
The literature searches in the manufacturer's submission were clearly reported with details of the search strategies and terms included. Three electronic databases were searched (Medline, Embase and the Cochrane Library) covering the period 1966 to May 2006.
In addition, one set of conference proceedings, American Society of Clinical Oncology (ASCO 2006), and Eli Lilly's unpublished data were searched.
Other relevant databases and conference sites which were not searched include Web of Science, Institute for Scientific Information (ISI) Proceedings and the European Society for Medical Oncology (ESMO) proceedings.
Search terms for electronic databases appropriately included a combination of free-text and index terms (non-small cell lung cancer) combined with drug names (pemetrexed, docetaxel or erlotinib) used as free-text terms.
Although the intervention under appraisal is pemetrexed for relapsed non-small-cell lung cancer (NSCLC), the search strategies used in the submission were appropriately expanded to include comparative studies of docetaxel, erlotinib and best supportive care (BSC) for further supporting evidence.
Inclusion and Exclusion Criteria
Details of inclusion and exclusion criteria are provided in Table 3-2 of the Evidence Review Group (ERG) Report (see the "Availability of Companion Documents" field) and are considered appropriate and complete.
A flow diagram and a table of included trials in the submission indicates that, of the 976 (non-duplicated) publications to which the inclusion criteria were applied, a total of nine trials was considered for inclusion in the review. This included one head to head trial that forms the basis of the direct comparison (JMEI), with an additional eight trials to inform indirect comparisons.
The searching exercise and application of inclusion criteria conducted by the ERG confirms the finding of only one relevant trial used in the direct comparison and an additional eight trials used in the indirect comparison.
Cost-Effectiveness
Identification and Description of Studies
The submission provided details of the electronic search strategy, including the search strings used for each database utilised. However, they did not include a record of the number of hits achieved by each search, nor the number of studies included and excluded at each stage, making replication of the search strategy impossible.
Studies were included in the economic review if they:
- Included a full or partial economic analysis
- Included patients with NSCLC receiving second-line treatment
- Were original and had not been reported elsewhere
Studies were excluded from the economic review if they:
- Were population based economic models
- Included NSCLC patients receiving first-line treatment
- Included small cell lung cancer patients
- Were editorials, letters or review articles describing data that had been reported elsewhere
- Were not English language papers
Using these inclusion and exclusion criteria, the company identified three full economic evaluations (none of which included pemetrexed as a comparator), eight studies evaluating costs and resources (two of which included pemetrexed), and 12 studies focusing on patient quality of life.
Studies identified under the heading 'resource use and cost' and 'quality of life' include papers on first-line therapies; whether this is a violation of the inclusion criteria is unclear. If it is not, other relevant studies could have been listed in the search results. Also, the company submission acknowledges that their review of quality of life studies needs to be updated.