Initial Flare Symptoms Resulting from Use of LHRH Agonist in Metastatic Prostate Cancer: Systematic Review and Economic Evaluation
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Initial Flare Symptoms Resulting from Use of LHRH Agonist in Metastatic Prostate Cancer: Systematic Review and Economic Evaluation by Yeesha Poon A thesis submitted in conformity with the requirements for the degree of Master of Science in Health Technology Assessment & Management Health Policy, Management and Evaluation University of Toronto © Copyright by Yeesha Poon, 2009 Initial Flare Symptoms Resulting from Use of LHRH Agonists in Metastatic Prostate Cancer: Systematic Review and Economic Evaluation Yeesha Poon Master of Science in Health Technology Assessment and Management Health Policy, Management and Evaluation University of Toronto 2009 ABSTRACT Background LHRH agonists decrease tumour size/activity by suppressing testosterone in prostate cancer; however, initial injection causes testosterone surge that triggers flare symptoms. Anti-androgen given with agonist may reduce/avoid flare symptoms. When LHRH antagonist/blocker is introduced, testosterone suppression is immediate, but there is uncertainty about significance of flare symptoms without anti-androgen. Objective Systematic review compared significance of flare symptoms avoided and cost utility analysis using modelling comparing incremental value of blocker (degarelix) OR agonist (goserelin)+anti-androgen (bicalutamide) VERSUS agonist alone in prostate cancer patients. ii Outcome Incremental cost/QALY of bone pain as flare symptom between treatments Results Thirteen studies were reviewed. There was no standard definition for flare symptoms or data on LHRH antagonist versus other treatments on flare. From societal perspective, goserelin+bicalutamide was dominated over goserelin alone and similarly, from public perspective, goserelin+bicalutamide had favourable cost effectiveness profile against goserelin. Conclusion With bone pain as clinical endpoint, LHRH agonist+anti-androgen had favourable cost-effectiveness profile compared to goserelin. iii ACKNOWLEDGMENTS I would like to thank my supervisor Dr. Eric Nauenberg and my committee member, Dr. Muhammad Mamdani in providing assistance in numerous ways in getting this thesis completed. I would also like to thank Dr. Wendy Ungar for providing directions for the thesis when needed. I would like to thank Rumona Dickson for her advice and help with the systematic review. I am grateful to the librarian, Klaus Boisen, who helped develop the search strategies and completed the literature searches. I am indebted to my fellow student Dinsie Williams for acting as the second reviewer of articles for the systematic review and for providing inputs for the thesis when needed. iv TABLE OF CONTENTS ABSTRACT...................................................................................................................ii ACKNOWLEDGMENTS ............................................................................................iv TABLE OF CONTENTS...............................................................................................v LIST OF TABLES........................................................................................................vi LIST OF FIGURES ................................................................................................... viii LIST OF APPENDICES...............................................................................................ix EXECUTIVE SUMMARY ...........................................................................................x Issue ...........................................................................................................................x Objectives .................................................................................................................xi Health Services Impact ...........................................................................................xiv Conclusion ..............................................................................................................xiv Chapter 1........................................................................................................................1 INTRODUCTION .........................................................................................................3 1.1 Background..........................................................................................................3 1.2 Current Clinical Practice......................................................................................3 1.2.1 Risk Stratification of Prostate Cancer....................................................5 1.2.2 Androgen Deprivation Therapy .............................................................6 1.2.3 LHRH Agonists .....................................................................................7 1.2.3 Issues with LHRH Agonists – Testosterone Surge................................7 1.3 Overview of New Technology.............................................................................8 Chapter 2......................................................................................................................10 SYSTEMATIC REVIEW............................................................................................10 2.1 The Issue ......................................................................................................10 2.2 Objectives ....................................................................................................10 2.3 Methods..............................................................................................................11 2.3.1 Literature search strategy............................................................................12 2.3.2 Selection criteria and method......................................................................13 2.3.3 Data extraction............................................................................................15 2.3.4 Strategy for quality assessment...................................................................15 2.4 Results................................................................................................................15 2.4.1 Quantity of research available ....................................................................15 2.4.2 Quality of included studies .........................................................................17 2.4.3 Data analyses and synthesis........................................................................17 a) Primary Endpoint - Clinical Flare....................................................................17 Disease Flare........................................................................................................18 b) Secondary Endpoint - Testosterone Surge.......................................................21 2.5 Summary......................................................................................................22 Chapter 3......................................................................................................................23 ECONOMIC ANALYSIS – 3-MONTH HORIZON ..................................................23 3.1 Review of Economic Studies: Methods.............................................................23 3.2 The Issue ............................................................................................................23 3.3 Primary Economic Evaluation: Methods...........................................................24 3.3.1 Types of economic evaluation ....................................................................24 3.3.2 Target population........................................................................................24 3.3.3 Comparators................................................................................................24 3.3.4 Perspective ..................................................................................................25 3.3.5 Time horizon...............................................................................................26 v 5.3.6 Modelling....................................................................................................26 3.3.7 Valuing outcomes .......................................................................................26 3.3.8 Utilities........................................................................................................26 3.3.9 Resource use and costs................................................................................28 3.3.10 Discount rate .............................................................................................33 3.3.11 Variability and uncertainty .......................................................................33 3.3.12 Summary of model assumptions...............................................................33 3.4 Primary Economic Evaluation: Results .............................................................33 3.4.1 Results – Societal Perspective ....................................................................33 3.4.2 Sensitivity Analyses – Societal Perspective ...............................................42 3.4.3 Results – Public Perspective .......................................................................45 3.4.4 Sensitivity Analyses – Public Perspective ..................................................47 3.5 Conclusion ...................................................................................................49 Chapter 4......................................................................................................................52 ECONOMIC ANALYSIS – 1 YEAR