458_1Page-Cover_TechReport.ai 3/25/2009 12:51:48 PM Canadian Agency for Agence canadienne Drugs and Technologies des médicaments et des in Health technologies de la santé technology report Anticonvulsants, Serotonin- HTA Norepinephrine Reuptake Inhibitors, Issue 116 and Tricyclic Antidepressants in January 2009 Management of Neuropathic Pain: A Meta-Analysis and Economic Evaluation Supporting Informed Decisions Until April 2006, the Canadian Agency for Drugs and Technologies in Health (CADTH) was known as the Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Publications can be requested from: CADTH 600-865 Carling Avenue Ottawa ON Canada K1S 5S8 Tel. (613) 226-2553 Fax (613) 226-5392 Email: [email protected] or downloaded from CADTH’s website: http://www.cadth.ca Cite as: Iskedjian M, Einarson TR, Walker J H, Jovey R, Moulin D. Anticonvulsants, Serotonin- Norepinephrine Reuptake Inhibitors, and Tricyclic Antidepressants in Management of Neuropathic Pain: A Meta-Analysis and Economic Evaluation [Technology report number 116]. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2009. Production of this report is made possible by financial contributions from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Ontario, Prince Edward Island, Saskatchewan, and Yukon. The Canadian Agency for Drugs and Technologies in Health takes sole responsibility for the final form and content of this report. The views expressed herein do not necessarily represent the views of Health Canada or any provincial or territorial government. Reproduction of this document for non-commercial purposes is permitted provided appropriate credit is given to CADTH. CADTH is funded by Canadian federal, provincial, and territorial governments. Legal Deposit – 2009 National Library of Canada ISBN: 978-1-897465-82-0 (print) ISBN: 978-1-897465-83-7 (online) H0458 – January 2009 PUBLICATIONS MAIL AGREEMENT NO. 40026386 RETURN UNDELIVERABLE CANADIAN ADDRESSES TO CANADIAN AGENCY FOR DRUGS AND TECHNOLOGIES IN HEALTH 600-865 CARLING AVENUE OTTAWA ON K1S 5S8 Canadian Agency for Drugs and Technologies in Health Anticonvulsants, Serotonin-Norepinephrine Reuptake Inhibitors, and Tricyclic Antidepressants in Management of Neuropathic Pain: A Meta-Analysis and Economic Evaluation Michael Iskedjian1 Thomas R. Einarson1,2* John H. Walker1,3 Roman Jovey4 Dwight Moulin5 January 2009 1 PharmIdeas Research and Consulting Inc., Oakville, ON, Canada 2 University of Toronto, Toronto, ON, Canada 3 Brock University, St. Catharines, ON, Canada 4 CPM Centres for Pain Management, Mississauga, ON, Canada 5 University of Western Ontario, London, ON, Canada *at time of analysis Reviewers These individuals kindly provided comments on this report: External Reviewers Kevin Rod, MD CCFP DAAPM David M. Bond, MBBChir MA MSc Director of Pain Program FRCPC Toronto Poly Clinic Assistant Professor, Anesthesiology Toronto, ON University of British Columbia Vancouver, BC Chris Skedgel, MDE Devidas Menon, PhD MHSA Research Health Economist Professor, Health Policy and Dalhousie University Management Capital Health University of Alberta Halifax, NS Edmonton, AB CADTH Peer Review Group Reviewers Simon Dagenais, DC PhD Rebecca N. Warburton, PhD Scientist Associate Professor, Public The Ottawa Hospital Administration Ottawa, ON University of Victoria Victoria, BC Industry: The following manufacturers were provided with an opportunity to comment on an earlier version of this report: Pfizer Canada Inc., Abbott Canada, Allergan Inc., Eli Lilly Canada Inc., Janssen-Ortho Inc., Novartis Pharmaceuticals Canada Inc., Solvay Pharmaceuticals Inc., Wyeth Pharmaceuticals, Lundbeck Canada Inc., and GlaxoSmithKline. All comments that were received were considered when preparing the final report. This report is a review of existing public literature, studies, materials, and other information and documentation (collectively the “source documentation”) that are available to CADTH. The accuracy of the contents of the source documentation on which this report is based is not warranted, assured, or represented in any way by CADTH, and CADTH does not assume responsibility for the quality, propriety, inaccuracies, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH takes sole responsibility for the final form and content of this report. The statements and conclusions in this report are those of CADTH and not of its panel members or reviewers. Authorship Michael Iskedjian was the Research Lead. He contributed conception, design, literature review, development of analysis plan, analysis, and interpretation of results. Thomas R. Einarson contributed to the conception, design, development of analysis plan and interpretation of results, and writing of report. This included identification of outcomes, i Anticonvulsants, Serotonin-Norepinephrine Reuptake Inhibitors, and Tricyclic Antidepressants in Management of Neuropathic Pain comparators, analytic approach, study horizon, and assistance in developing a pharmacoeconomic model. John H. Walker contributed to the design, development of analysis plan, modelling, analysis of results, and reviewing of the report. Roman Jovey contributed to the design and clinical relevance of the proposed data model, report reviews, and revisions for intellectual content. Dwight Moulin contributed to the design and clinical relevance of the proposed data model, report reviews, and revisions for intellectual content. All authors reviewed drafts of the report and approved the final report. Acknowledgements The authors are grateful to Rima Aziziyeh for the literature review, data extraction, and model parameterization, and Ruben Tavares and Sonia Eskedjian for editorial contribution to the final version of the report. Conflicts of Interest Michael Iskedjian has received funding for consultancy services and speakers fees, however none has been received from the above manufacturers for the indications in the report. John Walker has provided consultancy services, however none has been received from the above manufacturers for the indications in the report. Thomas Einarson has received funding for consulting services, presentations, seminars, and workshops for industry and government. Roman Jovey has received compensation for speakers fees, participating on advisory boards, consulting services, or writing projects from each of the following companies: Biovail Pharmaceuticals, Boehringer-Ingelheim Canada Ltd., Janssen-Ortho Inc., Merck Frosst Canada Ltd., Nycomed Canada Inc., Pfizer Canada Inc., Paladin Lab Inc., Purdue Pharma, Sanofi- Aventis Canada Inc., and Valeant Canada Ltd. Dwight Moulin has received compensation for speakers fees and consulting services from Purdue Pharma, Pfizer Canada Inc., Janssen-Ortho Inc. , Bayer Inc., Biovail Pharmaceuticals, Boehringer-Ingelheim Ltd. and Merck-Frosst Canada Ltd. and has conducted research for Purdue Pharma, Pfizer Canada Inc. and Janssen-Ortho Inc. Anticonvulsants, Serotonin-Norepinephrine Reuptake Inhibitors, and ii Tricyclic Antidepressants in Management of Neuropathic Pain iii Anticonvulsants, Serotonin-Norepinephrine Reuptake Inhibitors, and Tricyclic Antidepressants in Management of Neuropathic Pain EXECUTIVE SUMMARY The Issue Neuropathic pain places a burden on the public-payer health care system, the economy, and on patients’ quality of life. With the continued introduction of new treatments, there is uncertainty about whether currently recommended treatment options are sustainable, given scarce resources. An assessment is needed to identify optimal clinical- and cost-effective treatments of neuropathic pain. Objective The aim of this technology assessment was to assess the clinical and economic impact of first- line drugs in managing neuropathic pain. To achieve that aim, the research focused on answering the following research questions: • What are the clinical response rates from managing neuropathic pain with tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or anticonvulsants (ACs)? • What is the existing evidence of cost-effectiveness of using these drugs for managing neuropathic pain? • What drugs are cost-effective in managing neuropathic pain? • What would be the impact on public formulary drug budgets if cost-effective technologies were adopted? Clinical Review Methods: Two independent reviewers systematically searched MEDLINE, EMBASE, and Cochrane databases from inception to 2007. The references from retrieved studies and reviews of the topic were hand searched for further potential articles. Quality was assessed using Jadad’s method. The homogeneity of effects was determined using χ2 and I2. Data were combined using a random effects model. Results: We identified 13 studies (n=1,257) that evaluated the anticonvulsants (gabapentin and pregabalin), five that studied SNRIs (n=781), and 10 that focused on TCAs (n=249). One study evaluated TCAs and SNRIs. The average quality score was 81%±21%. For partial response rates, we analyzed 17 study arms (n=1,439), nine involving anticonvulsants (n=870), four that examined SNRIs (n=458), and four that studied TCAs (n=111). Rates for SNRIs were 66.0% [standard error (SE) 2.2%], for anticonvulsants they were 54.5% (SE 3.7%), and for TCAs they were 49.2% (SE 6.6%). For full response rates, 23 study arms were summarized. SNRIs had the higher response rate of 45.9% (SE 2.3%) and ACs