DOCSLIB.ORG

Of Rivaroxaban (Xarelto®)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Of Rivaroxaban (Xarelto®) SUBMISSION TO NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Single Technology Appraisal (STA) of Rivaroxaban (Xarelto®) Bayer Plc August 2011 List of Abbreviations AC Anticoagulation ACS Acute Coronary Syndrome ACTS Anti-Clot Treatment Scale AE(s) Adverse events AF Atrial Fibrillation AFNET German Atrial Fibrillation Competence NETwork ALT Alanine Transaminase ASA Acetylsalicylic Acid (aspirin) AST Aspartate aminotransferase BMI Body Mass Index BNF British National Formulary CABG Coronary Artery Bypass Graft (surgery) CEA Cost Effectiveness Analysis CEAC Cost Effectiveness Acceptability Curve CEC Clinical Events Committee CHADS2 Congestive heart failure, Hypertension, Age, Diabetes and history of Stroke or TIA (doubled) CHA2DS2-VASc Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular Disease, Age 65–74, and Sex category (female)] CI Confidence Interval CNS Central Nervous System COPD Chronic Obstructive Pulmonary Disease CrCL Creatinine Clearance cTTR Centre Time in Therapeutic Range CV Cardiovascular DSMB Data Safety and Monitoring Board DVT Deep Vein Thrombosis ECG Electrocardiogram EHRA European Heart Rhythm Association EM(E)A European Medicines Agency ESC European Society of Cardiology FAD Final Appraisal Determination (in relation to NICE) FDA Food & Drug Administration GCP Good Clinical Practice GP General Practitioner HIV Human Immunodeficiency Virus HR Hazard Ratio HRG Healthcare Resource Groups HRQoL Health Related Quality of Life IC Intracranial ICER Incremental Cost-Effectiveness Ratio ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICUR Incremental Cost-Utility Ratio IDMC Independent Data Monitoring Committee INR International Normalised Ratio ITT Intention To Treat IVRS Interactive Voice Response System LFT(s) Liver Function Test(s) LMWH Low Molecular Weight Heparin LOS Length of Stay 1 LV Left Ventricular LVEF Left Ventricular Ejection Fraction LY Life-Years LYG Life-Years Gained MedDRA Medical Dictionary for Regulatory Activities mg Milligram(s) MI Myocardial Infarction min minute ml millilitre mmHg millimeters Mercury MRI Magnetic Resonance Imaging NHS National Health Service NICE National Institute for Health and Clinical Excellence NMA Network Meta-Analysis NRAF National Registry of Atrial Fibrillation NVAF Non-Valvular Atrial Fibrillation NYHA New York Heart Association OAC Oral Anticoagulation / Anticoagulant Od Once daily OWSA One Way Sensitivity Analysis PbR Payment by Results PCI Percutaneous Coronary Intervention PCT Primary Care Trust PE Pulmonary Embolism PP Per Protocol PPI Proton Pump Inhibitor PSA Probabilistic Sensitivity Analysis PSS Personal Social Services PSSRU Personal Social Services Research Unit PTS Patient Transport Service QALY Quality Adjusted Life Years QOF Quality and Outcomes Framework RCT Randomised Controlled Trial RF Risk Factor ROCKET AF Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation RR Relative Risk SAE Serious Adverse Event SE Systemic Embolism SIGN Scottish Intercollegiate Guidelines Network SMC Scottish Medicines Consortium SOT Safety On-Treatment (population) SPAF Stroke Prevention in Atrial Fibrillation SPC Summary of Product Characteristics TIA Transient Ischaemic Attack TIMI Thrombolysis in Myocardial Infarction (in relation to bleeding) TSQM Treatment Satisfaction Questionnaire TTR Time in Therapeutic Range Tx Therapy / Treatment UK United Kingdom ULN Upper Limit of Normal US(A) United States (of America) 2 VKA Vitamin K Antagonist vs versus VTE Venous Thromboembolism 3 Table of Contents Executive summary....................................................................................................................... 9 Section A – Decision problem ................................................................................................. 15 1 Description of technology under assessment ..................................................................... 15 2 Context................................................................................................................................ 20 3 Equity and equality.............................................................................................................. 27 4 Statement of the decision problem...................................................................................... 28 Section B – Clinical and cost effectiveness ........................................................................... 31 5 Clinical evidence ................................................................................................................. 31 6 Cost effectiveness.............................................................................................................114 Section C – Implementation................................................................................................... 266 7 Assessment of factors relevant to the NHS and other parties .......................................... 266 8 References........................................................................................................................ 278 9 Appendices ....................................................................................................................... 289 Table of tables Table 1. Base-case cost-effectiveness results...................................................................... 11 Table 2 Cost effectiveness results – poorly controlled on warfarin....................................... 12 Table 3 Cost effectiveness results – warfarin naive.............................................................. 12 Table 4 Cost effectiveness results – warfarin unsuitable...................................................... 13 Table 5 Incremental cost effectiveness results – aspirin and no treatment .......................... 13 Table 6 Cost effectiveness results vs dabigatran ................................................................. 14 Table 7. Unit costs of technology being appraised ............................................................... 18 Table 8. Eligible population................................................................................................... 21 Table 9. Eligibility criteria used in search strategy ................................................................ 32 Table 10. List of relevant RCTs ............................................................................................ 34 Table 11. Key features of rivaroxaban phase III RCT in the prevention of stroke and thromboembolism in AF(23-28) ............................................................................................ 37 Table 12. Treatment Assignments ........................................................................................ 41 Table 13. Eligibility criteria in the ROCKET AF study(24) .................................................... 43 Table 14. Demographic and baseline data of ROCKET AF study participants (ITT population) ............................................................................................................................ 47 Table 15. Definitions of observation periods and study populations for statistical analysis(26) .............................................................................................................................................. 53 Table 16. Quality assessment of RCTs ................................................................................ 62 Table 17. Primary Trial Endpoint: Stroke and Non-CNS Embolism...................................... 66 Table 18. Incidence and event rates of secondary efficacy endpoints as adjudicated by CEC (Safety / on-treatment population, excluding Czech site)(28) ............................................... 73 Table 19. Incidence and event rates of secondary efficacy endpoints as adjudicated by CEC (ITT to Site Notification population, excluding Czech site)(26) ............................................. 74 Table 20. Hierarchical testing – Event rate, Hazard Ratio and 95% CI for Time to the first occurrence of Efficacy Endpoints (Adjudicated by CEC)(23;26;28)...................................... 79 Table 21. Percentage (Median) of INR Values in therapeutic range for warfarin by region (safety population) ................................................................................................................ 80 Table 22: Percentage of INR Values in range of 2-3 for Warfarin (Imputed) by Baseline CHADS2 Score (Safety Analysis Set) ................................................................................... 81 Table 23. Treatment effects by quartiles of centre Time in Therapeutic Range (safety on treatment population)*† (28) ................................................................................................. 82 Table 24. Summary of the trials used to conduct the network meta-analysis....................... 87 Table 25. Summary of odds ratios for rivaroxaban compared to selected comparators....... 90 Table 26. Results of Primary Safety Endpoint (23;26) based on safety on treatment population ............................................................................................................................. 98 Table 27. Major bleeding by site*.......................................................................................... 99 Table 28. Adverse event summary ....................................................................................
Load more

Recommended publications
  • (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al
    USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • Characterising the Risk of Major Bleeding in Patients With
    EU PE&PV Research Network under the Framework Service Contract (nr. EMA/2015/27/PH) Study Protocol Characterising the risk of major bleeding in patients with Non-Valvular Atrial Fibrillation: non-interventional study of patients taking Direct Oral Anticoagulants in the EU Version 3.0 1 June 2018 EU PAS Register No: 16014 EMA/2015/27/PH EUPAS16014 Version 3.0 1 June 2018 1 TABLE OF CONTENTS 1 Title ........................................................................................................................................... 5 2 Marketing authorization holder ................................................................................................. 5 3 Responsible parties ................................................................................................................... 5 4 Abstract ..................................................................................................................................... 6 5 Amendments and updates ......................................................................................................... 7 6 Milestones ................................................................................................................................. 8 7 Rationale and background ......................................................................................................... 9 8 Research question and objectives .............................................................................................. 9 9 Research methods ....................................................................................................................
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • Pharmaceutical Appendix to the Harmonized Tariff Schedule
    Harmonized Tariff Schedule of the United States (2019) Revision 13 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2019) Revision 13 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub
    US 20090005722A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub. Date: Jan. 1, 2009 (54) SKIN-CONTACTING-ADHESIVE FREE Publication Classification DRESSING (51) Int. Cl. Inventor: Barbara Jennings-Spring, Jupiter, A61N L/30 (2006.01) (76) A6F I3/00 (2006.01) FL (US) A6IL I5/00 (2006.01) Correspondence Address: AOIG 7/06 (2006.01) Irving M. Fishman AOIG 7/04 (2006.01) c/o Cohen, Tauber, Spievack and Wagner (52) U.S. Cl. .................. 604/20: 602/43: 602/48; 4771.5; Suite 2400, 420 Lexington Avenue 47/13 New York, NY 10170 (US) (57) ABSTRACT (21) Appl. No.: 12/231,104 A dressing having a flexible sleeve shaped to accommodate a Substantially cylindrical body portion, the sleeve having a (22) Filed: Aug. 29, 2008 lining which is substantially non-adherent to the body part being bandaged and having a peripheral securement means Related U.S. Application Data which attaches two peripheral portions to each other without (63) Continuation-in-part of application No. 1 1/434,689, those portions being circumferentially adhered to the sleeve filed on May 16, 2006. portion. Patent Application Publication Jan. 1, 2009 Sheet 1 of 9 US 2009/0005722 A1 Patent Application Publication Jan. 1, 2009 Sheet 2 of 9 US 2009/0005722 A1 10 8 F.G. 5 Patent Application Publication Jan. 1, 2009 Sheet 3 of 9 US 2009/0005722 A1 13 FIG.6 2 - Y TIII Till "T fift 11 10 FIG.7 8 13 6 - 12 - Timir" "in "in "MINIII.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Study Protocol
    Protocol 3-001 Confidential 28APRIL2017 Version 4.1 Asahi Kasei Pharma America Corporation Synopsis Title of Study: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Assess the Safety and Efficacy of ART-123 in Subjects with Severe Sepsis and Coagulopathy Name of Sponsor/Company: Asahi Kasei Pharma America Corporation Name of Investigational Product: ART-123 Name of Active Ingredient: thrombomodulin alpha Objectives Primary: x To evaluate whether ART-123, when administered to subjects with bacterial infection complicated by at least one organ dysfunction and coagulopathy, can reduce mortality. x To evaluate the safety of ART-123 in this population. Secondary: x Assessment of the efficacy of ART-123 in resolution of organ dysfunction in this population. x Assessment of anti-drug antibody development in subjects with coagulopathy due to bacterial infection treated with ART-123. Study Center(s): Phase of Development: Global study, up to 350 study centers Phase 3 Study Period: Estimated time of first subject enrollment: 3Q 2012 Estimated time of last subject enrollment: 3Q 2018 Number of Subjects (planned): Approximately 800 randomized subjects. Page 2 of 116 Protocol 3-001 Confidential 28APRIL2017 Version 4.1 Asahi Kasei Pharma America Corporation Diagnosis and Main Criteria for Inclusion of Study Subjects: This study targets critically ill subjects with severe sepsis requiring the level of care that is normally associated with treatment in an intensive care unit (ICU) setting. The inclusion criteria for organ dysfunction and coagulopathy must be met within a 24 hour period. 1. Subjects must be receiving treatment in an ICU or in an acute care setting (e.g., Emergency Room, Recovery Room).
    [Show full text]
  • Search Strategy, Baseline Risk Coronavirus and Prophylaxis For
    Supplement 7: Search Strategy, Baseline Risk Coronavirus and prophylaxis for thrombotic events Search narrative, 23 July 2020 Bibliographic databases: EMBASE (1974 to, 22 July 2020) Epistemonikos COVID-19 Evidence (21 July 2020) (includes records from Cochrane Database of Systematic Reviews, Pubmed, EMBASE, CINAHL, PsycINFO, LILACS, Database of reviews of Effects, The Campbell Collaboration online library, JBI Database of Systematic Reviews and Implementation Reports, EPPI-Centre Evidence Library) MEDLINE (1946 to, 23 July 2020) SCOPUS (19 July 2020) WHO Global Research Database (COVID-19) (20 July 2020) Trial/study Databases: Cochrane COVID-19 study register (23 July 2020) (includes records from ClinicalTrials.gov, WHO ICTRN, and PubMed) CYTEL map of ongoing [COVID-19] clinical trials (20 July 2020) (WHO International Clinical Trials Registry Platform, European Clinical Trials Registry, clinicaltrials.gov, Chinese Clinical Trial Registry, German Clinical Trials registry, Japan Primary Registries Network, Iranian Clinical Trial Registry, and Australian New Zealand Clinical Trials Registry) Results were downloaded from sources and deduplicated in EndNote. Results from BioRxiV, ChemRxiV, MedRxiV (preprints indexed in Medline and Epistemonikos), or protocols for clinical trials were removed as they were beyond the scope of the search. COCHRANE COVID-19 (https://covid-19.cochrane.org/) Search 1: anticoagula* or anti-coagula* or coagulation or thromb* or antithromb* or antiplatelet* or heparin or LMWH or aspirin or embol* or phlebothrombos*
    [Show full text]
  • 1 SUPPLEMENTAL MATERIAL the Effectiveness of Interventions for The
    SUPPLEMENTAL MATERIAL The effectiveness of interventions for the implementation of thromboprophylaxis in hospitalized patients at risk for venous thromboembolism: an updated abridged Cochrane systematic review and meta-analysis of Randomized Controlled Trials (RCT). Susan R Kahn1,2,3, Gisèle Diendéré2, David R Morrison2, Alexandre Piché4, Kristian B Filion2,5, Adi J Klil-Drori1,2, James D Douketis6, Jessica Emed7, André Roussin8, Vicky Tagalakis2,3, Martin Morris9, William Geerts10 1Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada 2Centre for Clinical Epidemiology and Community Studies, Jewish General Hospital, McGill University, Montreal, Canada 3Division of Internal Medicine and Department of Medicine, McGill University, Montreal, Canada 4Department of Mathematics and Statistics, McGill University, Montreal, Canada 5Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada 6Department of Medicine, McMaster University and St. Josephs Hospital, Hamilton, Canada 7Department of Nursing, Jewish General Hospital, Montreal, Canada 8Department of Medicine, University of Montreal and Thrombosis Canada, Montreal, Canada 9Schulich Library of Physical Sciences, Life Sciences and Engineering, McGill University, Montreal, Canada 10Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada Corresponding author: Dr Susan R Kahn MD MSc FRCPC GCBA Canada Research Chair Professor of Medicine, McGill University Director, McGill Thrombosis Fellowship Director, JGH Centre of Excellence in Thrombosis and Anticoagulation Care Division of Internal Medicine & Center for Clinical Epidemiology Jewish General Hospital 3755 Cote Ste. Catherine Room B-304.16 Montreal QC CANADA H3T 1E2 Tel. + 1 514 340 8222 X 24667 or 514 340 7587 Fax. 514 340 7564 E-mail: [email protected] 1 Search Criteria 1.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]