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Fludarabine As First Line Therapy for Chronic Lymphocytic Leukaemia

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Fludarabine As First Line Therapy for Chronic Lymphocytic Leukaemia Fludarabine as first line therapy for CLL FLUDARABINE AS FIRST LINE THERAPY FOR CHRONIC LYMPHOCYTIC LEUKAEMIA A West Midlands Health Technology Assessment Collaboration report Authors: Sarah Hancock, Research Reviewer and Analyst Beverley Wake, Systematic Reviewer Chris Hyde, Senior Lecturer in Public Health Correspondence to: Sarah Hancock ARIF Department of Public Health & Epidemiology University of Birmingham Edgbaston BIRMINGHAM B15 2TT Email: [email protected] Report number: 42 ISBN No: 0-7044-2412-6 © Copyright, West Midlands Health Technology Assessment Collaboration Department of Public Health and Epidemiology The University of Birmingham 2003. Fludarabine as first line therapy for CLL Fludarabine as first line therapy for CLL West Midlands Health Technology Assessment Collaboration (WMHTAC) The WMHTAC produces rapid systematic reviews about the effectiveness of health care interventions and technologies, in response to requests from West Midlands Primary Care Trusts. Reviews take approximately 6 months and aim to give a timely and accurate analysis of the available evidence, with an economic analysis (usually a cost-utility analysis) of the intervention accompanied by a statement of the quality of the evidence. Contributions of authors Sarah Hancock was the lead reviewer and the chief author undertaking the collection and collation of the evidence for this review. SH and Beverley Wake undertook independent data extraction and quality assessment. Chris Hyde gave advice on the formulation of the question and overall process of the review, undertook the review of economic evaluations and helped with some of the writing and structuring of the review. Conflicts of interest This work has been undertaken by people funded by the NHS. The authors have received no funding from any sponsor in this work. Acknowledgements Anne Fry-Smith Dr Rod Taylor Dr Steven Johnson Dr Christopher Fegan Dr Peter Rose Janine Dretzke Josie Sandercock Fludarabine as first line therapy for CLL Fludarabine as first line therapy for CLL West Midlands Regional Evaluation Panel Recommendation: The recommendation for the use of Fludarabine as first line therapy for chronic lymphocytic leukaemia was: Borderline – because of the relatively high cost per QALY Clinicians and purchasers should be encouraged to support the MRC trial. Anticipated expiry date: 2005 (or until such time as the MRC trial reports) • This report was completed in September 2002 • The searches were completed in January 2002 Fludarabine as first line therapy for CLL Fludarabine as first line therapy for CLL CONTENTS 1. EXECUTIVE SUMMARY................................................................................................ 1 2. AIM OF THE REVIEW..................................................................................................... 6 2.1 The technology........................................................................................................... 6 2.2 The condition.............................................................................................................. 6 2.3 Objective of the report................................................................................................ 6 3. BACKGROUND................................................................................................................ 6 3.1 Chronic lymphocytic leukaemia (CLL) - Description ............................................... 6 3.2 Chronic lymphocytic leukaemia (CLL) - Epidemiology ........................................... 7 3.3 Chronic lymphocytic leukaemia (CLL) - Aetiology .................................................. 8 3.4 Treatment - Established first-line treatments ............................................................. 9 3.5 Treatment - Chlorambucil as first-line treatment....................................................... 9 3.6 Current service cost.................................................................................................. 10 3.7 Fludarabine – Description of new intervention........................................................ 10 3.7.1 Intravenously administered fludarabine ........................................................... 10 3.7.2 Orally administered fludarabine....................................................................... 10 3.8 Fludarabine - Effectiveness evidence of as second line treatment........................... 11 3.9 Fludarabine - Side effects of treatment .................................................................... 12 4. CLINICAL EFFECTIVENESS ....................................................................................... 13 4.1 Clinical Effectiveness - Methods ............................................................................. 13 4.1.1 Search Strategy................................................................................................. 13 3.1.2 Inclusion and exclusion criteria........................................................................ 13 3.1.3 Quality assessment strategy.............................................................................. 14 3.1.4 Data extraction strategy.................................................................................... 14 3.1.5 Analysis............................................................................................................ 14 4.2 Clinical Effectiveness - Results................................................................................ 14 4.2.1 Quality and quantity of data available.............................................................. 14 4.2.2 Effectiveness of fludarabine compared with chlorambucil alone at standard dosage 15 4.2.3 Effectiveness of fludarabine compared with other first line therapies............. 21 3.2.4 Ongoing Trials of Fludarabine in Chronic Lymphocytic Leukaemia .............. 22 4.3 Clinical Effectiveness - Discussion.......................................................................... 22 5. ECONOMIC EVALUATION.......................................................................................... 23 5.1 Systematic Review of Economic Evaluations - Methods ........................................ 24 5.1.1 Search Strategy................................................................................................. 24 5.1.2 Inclusion Criteria and Analysis ........................................................................ 24 5.2 Systematic review of economic evaluations – results.............................................. 24 5.2.1 Number of included studies.............................................................................. 24 5.2.2 Economic evaluations of fludarabine used first line ........................................ 24 5.2.3 Economic evaluations of fludarabine used second line.................................... 26 5.3 Systematic review of economic evaluations - conclusions ...................................... 29 5.4 Cost Analysis - Methods .......................................................................................... 29 5.5 Cost Analysis - Results............................................................................................. 29 5.6 Cost Analysis - Discussion....................................................................................... 32 5.7 Modelling - methods ................................................................................................ 33 5.8 Modelling - results.................................................................................................... 35 5.9 Modelling – discussion............................................................................................. 36 6. DISCUSSION .................................................................................................................. 37 7. REFERENCES................................................................................................................. 59 Fludarabine as first line therapy for CLL FIGURES Figure 1. Identification of RCTs included in systematic review of effectiveness .................. 15 Figure 2. Decision analytic model of fludarabine compared with chlorambucil .................... 33 TABLES Table 1 - Binet staging system for CLL..................................................................................... 8 Table 2 - Rai staging system for CLL ....................................................................................... 8 Table 3 - Characteristics of RCT comparing fludarabine to chlorambucil alone at standard dosage............................................................................................................................... 17 Table 4 - Quality assessment of RCT comparing fludarabine to chlorambucil alone at standard dosage............................................................................................................................... 18 Table 5 - Results of RCT comparing fludarabine to chlorambucil alone at standard dosage.. 19 Table 6 - Summary of cost-effectiveness data given in NICE guidance, and the cost and effectiveness data on which based (additional information drawn from Cost- Effectiveness Annexe)...................................................................................................... 26 Table 7 - Summary of key details of economic evaluation contained in the Schering Health Care Ltd submission to NICE identified in report by Hyde et al..................................... 28 Table 8 - The resource requirements for the first-line treatment of B-CLL
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