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 (see the "Companion Documents" field).
Data Sources
Fifteen electronic bibliographic databases were searched to identify all literature relating to the clinical and cost effectiveness of rituximab for the treatment of aggressive non-Hodgkin's lymphoma.
Clinical Effectiveness
This systematic review was carried out according to the recommendations of the QUOROM statement (Appendix 4 of the Assessment Report [see the "Availability of Companion Documents" field]).
Search Strategy
The search aimed to identify all literature relating to the clinical and cost effectiveness of rituximab (MabThera®) for the treatment of aggressive non-Hodgkin's lymphoma. The main searches were conducted in August and September 2002.
Sources Searched
Fifteen electronic bibliographic databases were searched, covering biomedical, science, social science, health economic and grey literature.
In addition, the reference lists of relevant articles and sponsor submissions were hand searched and various health services research related resources were consulted via the Internet. These included health economics and health technology assessment organisations, guideline producing agencies, generic research and trials registers, and specialist sites. A list of additional sources is given in Appendix 6 of the Assessment Report (see the "Availability of Companion Documents" field). Citation searches were conducted on the key paper and its author using the Science and Social Science Citation Index facilities, Medline and Embase.
Search Terms
A combination of free-text and thesaurus terms were used. 'Population' search terms (e.g., lymphoma, lymphocytes, non-Hodgkin's, high-grade, intermediate-grade, large cell) were combined with 'intervention' terms (e.g., Rituximab, MabThera, Rituxan, antineoplastic agents, etc.).
Search Restrictions
No language, study/publication, or date restrictions were applied to the main searches. The main searches performed in Medline and Embase included filters for systematic reviews/meta-analyses, economic/QoL evaluations, controlled trials, and guidelines, in order to assist with the identification of these types of articles (all other study types were also saved).
Inclusion and Exclusion Criteria
The structured title was formulated as, 'rituximab plus CHOP versus CHOP alone for DLBCL.' Comparative studies were included if: (a) the study population had untreated diffuse large-B-cell lymphoma (DLBCL) that had been diagnosed according to the Revised European American Lymphoma (REAL), or REAL-World Health Organization (WHO) classificatory schema; (b) the study intervention was rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP), and the study comparator was CHOP alone (where the cycles of CHOP in each arm were identical); and, (c) study endpoints included event-free survival (see below for definition). There were no language restrictions and studies reported only in abstract form were reported.
Reasons for exclusion were: (a) a non-comparative study design; (b) populations other than those described above; (c) absence of the interventions and/or comparators described above; and, (d) absence of 'event-free survival as the primary outcome of interest'.
The abstracts of potentially relevant citations were reviewed. After examining the full manuscripts of all potentially relevant abstracts, those deemed to be potential randomised controlled trials relating directly to the structured title were obtained.
Cost Effectiveness
One economic evaluation of rituximab in combination with CHOP (R-CHOP) versus CHOP was supplied by the manufacturer. Costs were estimated through resource use data taken from the published trial and the unpublished sponsor submission. Unit costs were taken from published sources, where available.
Refer to the "Cost Analysis" field for more information.