CHAPTER ONE: INTRODUCTION... 1 STUDY OBJECTIVES... 1 REASONS FOR DOING THIS STUDY... 1 INTENDED AUDIENCE... 2 SCOPE OF THE STUDY... 2 METHODOLOGY... 2 INFORMATION SOURCES... 2 ABOUT THE AUTHOR... 3 RELATED BCC RESEARCH REPORTS... 3 BCC ONLINE SERVICES... 3 DISCLAIMER... 4 CHAPTER TWO: EXECUTIVE SUMMARY... 5 EXECUTIVE SUMMARY... 5 SUMMARY TABLE WORLDWIDE REVENUE OF ANTIEMETICS, THROUGH 2015 ($ MILLIONS)... 6 SUMMARY FIGURE WORLDWIDE REVENUE OF ANTIEMETICS, 2008-2015 ($ MILLION)... 6 CHAPTER THREE: OVERVIEW... 7 STAGES IN NAUSEA AND VOMITING... 7 TYPES OF EMESIS... 8 RELATIONSHIP BETWEEN RECEPTORS AND NAUSEA... 8 THE GI TRACT... 9 THE CHEMORECEPTOR TRIGGER ZONE (CTZ)... 9 THE VESTIBULAR APPARATUS... 9 THE CEREBRAL CORTEX... 10 HISTORY... 10 HISTORY OF PATHOPHYSIOLOGY... 10 HISTORY OF ANTIEMETIC THERAPY... 10 TABLE 1 HISTORY OF ANTIEMETIC THERAPY... 10 TABLE 1 (CONTINUED)... 11 TABLE 2 HISTORY OF SEROTONIN AND 5-HT RECEPTORS... 11 TABLE 3 HISTORY OF TACHYKININS AND NEUROKININ RECEPTORS... 12 TABLE 4 HISTORY OF CORTICOSTEROIDS... 12 TABLE 5 HISTORY OF DOPAMINE AND DOPAMINE RECEPTORS... 12 CAUSES OF EMESIS AND ITS THERAPY... 13 VESTIBULAR INVOLVEMENT... 13 OBSTRUCTION... 14 MIND... 14 INFECTION, IRRITATION, AND INFLAMMATION... 15 TOXINS... 15 TABLE 6 CAUSES OF EMESIS AND THE THERAPY INVOLVED... 16
CHAPTER FOUR: TYPE OF ANTIEMETIC DRUGS... 17 TYPES OF ANTIEMETIC DRUGS... 17 5-HTЗ RECEPTOR ANTAGONISTS... 17 TABLE 7 5-HTЗ RECEPTOR ANTAGONISTS DRUG PRODUCTS AS ANTIEMETICS... 18 NK1 RECEPTOR ANTAGONISTS... 18 TABLE 8 5NK1 RECEPTOR ANTAGONISTS DRUG PRODUCTS AS ANTIEMETICS... 19 ANTIHISTAMINES (HI ANTIHISTAMINE RECEPTOR ANTAGONISTS):... 19 TABLE 9 ANTIHISTAMINES DRUG PRODUCTS AS ANTIEMETICS... 19 TABLE 9 (CONTINUED)... 20 DOPAMINE ANTAGONISTS... 20 TABLE 10 DOPAMINE ANATAGONISTS, DRUG PRODUCTS AS ANTIEMETICS... 21 STEROID-CORTICOSTEROIDS... 21 TABLE 11 STEROIDS-CORTICOSTEROIDS, DRUG PRODUCTS AS ANTIEMETICS... 22 CANNABINOIDS... 22 TABLE 12 CANNABINOIDS, DRUG PRODUCTS AS ANTIEMETICS... 23 BENZODIAZEPINES... 23 TABLE 13 BENZODIAZEPINES, DRUG PRODUCTS AS ANTIEMETICS... 24 ANTICHOLINERGICS... 25 TABLE 14 ANTICHOLENERGIC DRUG PRODUCTS AS ANTIEMETICS... 25 OTHERS... 25 TABLE 15 OTHER PRODUCTS AS ANTIEMETICS... 26 TABLE 16 NON-PHARMACEUTICAL THERAPIES... 26 TABLE 16 (CONTINUED)... 27 CHAPTER FIVE: REGULATORY ASPECTS... 28 TABLE 17 APPROVALS OF ANTIEMETICS, 2007 TO APRIL 2010... 28 TABLE 17 (CONTINUED)... 29 TABLE 17 (CONTINUED)... 30 TABLE 17 (CONTINUED)... 31 TABLE 17 (CONTINUED)... 32 TABLE 17 (CONTINUED)... 33 TABLE 18 REGULATORY CHANGES OF ANTIEMETICS, 2007 TO APRIL 2010, BY ACTIVE INGREDIENT... 34 TABLE 18 (CONTINUED)... 35 TABLE 18 (CONTINUED)... 36 TABLE 19 SAFETY ALERTS FOR ANTIEMETICS, 2007 TO APRIL 2010, BY ACTIVE INGREDIENT... 36 TABLE 19 (CONTINUED)... 37
REGULATORY UPDATES: APPROVAL, DENIALS AND AGREEMENTS... 37 REGULATORY UPDATES: APPROVAL, (CONTINUED)... 38 CHAPTER SIX: INDUSTRY STRUCTURE... 39 MANUFACTURERS/PRODUCTS FOR ANTIEMETICS... 39 TABLE 20 LEADING MANUFACTURERS OF 5-HT3 RECEPTOR ANTAGONISTS... 39 TABLE 20 (CONTINUED)... 40 TABLE 21 LEADING MANUFACTURERS OF NK-1 RECEPTOR ANTAGONISTS... 40 TABLE 22 LEADING MANUFACTURERS OF H1 RECEPTOR ANTAGONISTS... 40 TABLE 22 (CONTINUED)... 41 TABLE 23 LEADING MANUFACTURERS OF DOPAMINE ANTAGONISTS... 41 TABLE 23 (CONTINUED)... 42 TABLE 24 LEADING MANUFACTURERS/ SUPPLIERS OF STEROIDS-CORTICOSTEROIDS... 42 TABLE 25 LEADING MANUFACTURERS/ SUPPLIERS OF CANNABINOIDS... 43 TABLE 26 LEADING MANUFACTURERS/ SUPPLIERS OF BENZODIAZEPINES... 43 TABLE 27 LEADING MANUFACTURERS/ SUPPLIERS OF ANTICHOLINERGICS... 43 MARKET SHARES OF INDUSTRY LEADERS... 44 5-HT3 RECEPTOR ANATAGONISTS... 44 TABLE 28 WORLDWIDE MARKET SHARES OF 5-HT3 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 44 FIGURE 1 WORLDWIDE MARKET SHARES OF 5-HT3 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 45 NK-1 RECEPTOR ANATAGONISTS... 45 TABLE 29 WORLDWIDE MARKET SHARES OF NK-1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 45 H1 RECEPTOR ANATAGONISTS... 46 TABLE 30 WORLDWIDE MARKET SHARES OF H1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 46 FIGURE 2 WORLDWIDE MARKET SHARES OF H1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 47 DOPAMINE ANATAGONISTS... 47 TABLE 31 WORLDWIDE MARKET SHARES OF DOPAMINE ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 47 FIGURE 3 WORLDWIDE MARKET SHARES OF DOPAMINE ANTAGONISTS USED AS ANTIEMETICS, 2009 (%)... 48 STEROIDS-CORTICOSTEROIDS... 48
TABLE 32 WORLDWIDE MARKET SHARES OF STEROIDS- CORTICOSTEROIDS USED AS ANTIEMETICS, 2009 (%)... 48 FIGURE 4 WORLDWIDE MARKET SHARES OF STEROIDS- CORTICOSTEROIDS USED AS ANTIEMETICS, 2009 (%)... 49 CANNABINOIDS... 49 TABLE 33 WORLDWIDE MARKET SHARES OF CANNABINOIDS USED AS ANTIEMETICS, 2009 (%)... 49 FIGURE 5 WORLDWIDE MARKET SHARES OF CANNABINOIDS USED AS ANTIEMETICS, 2009 (%)... 50 BENZODIAZEPINES... 50 TABLE 34 WORLDWIDE MARKET SHARES OF BENZODIAZEPINES USED AS ANTIEMETICS, 2009 (%)... 50 FIGURE 6 WORLDWIDE MARKET SHARES OF BENZODIAZEPINES USED AS ANTIEMETICS, 2009 (%)... 51 ANTICHOLINERGICS... 51 TABLE 35 WORLDWIDE MARKET SHARES OF ANTICHOLINERGICS USED AS ANTIEMETICS, 2009 (%)... 51 FIGURE 7 WORLDWIDE MARKET SHARES OF ANTICHOLINERGICS USED AS ANTIEMETICS, 2009 (%)... 52 CHAPTER SEVEN: NEW DEVELOPMENTS... 53 NEW DEVELOPMENTS... 53 TABLE 36 WORLDWIDE NEW DEVELOPED DRUGS SINCE 2003... 54 TABLE 37 PIPELINE ANTIEMETICS... 55 TABLE 37 (CONTINUED)... 56 RECENT UPDATES FROM THE ANTIEMETIC WORLD... 56 RECENT UPDATES FROM THE (CONTIUED)... 57 RECENT UPDATES FROM THE (CONTIUED)... 58 CHAPTER EIGHT: MARKET ANALYSIS... 59 5-HT3 RECEPTOR ANTAGONISTS... 59 MARKET OVERVIEW... 60 Market Overview (Continued)... 61 MARKET REVENUE... 62 TABLE 38 WORLDWIDE MARKET FOR 5-HT3 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 62 FIGURE 8 WORLDWIDE MARKET FOR 5-HT3 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 63 NK1 RECEPTOR ANTAGONISTS... 63 MARKET OVERVIEW... 64 MARKET REVENUE... 64
TABLE 39 WORLDWIDE MARKET FOR NK-1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 65 FIGURE 9 WORLDWIDE MARKET FOR NK-1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 65 H1 RECEPTOR ANTAGONISTS... 66 MARKET OVERVIEW... 66 MARKET REVENUE... 67 TABLE 40 WORLDWIDE MARKET FOR H1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 67 FIGURE 10 WORLDWIDE MARKET FOR H1 RECEPTOR ANTAGONISTS USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 67 DOPAMINE ANTAGONISTS... 68 MARKET OVERVIEW... 68 MARKET REVENUE... 69 TABLE 41 WORLDWIDE MARKET FOR DOPAMINE ANTAGONISTS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 69 FIGURE 11 WORLDWIDE MARKET FOR DOPAMINE ANTAGONISTS USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 70 STEROIDS -CORTICOSTEROIDS... 70 MARKET OVERVIEW... 70 MARKET REVENUE... 71 TABLE 42 WORLDWIDE MARKET FOR STEROIDS- CORTICOSTEROIDS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 72 FIGURE 12 WORLDWIDE MARKET FOR STEROIDS- CORTICOSTEROIDS USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 72 CANNABINOIDS... 72 MARKET OVERVIEW... 73 MARKET REVENUE... 73 TABLE 43 WORLDWIDE MARKET FOR CANNABINOIDS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 74 FIGURE 13 WORLDWIDE MARKET FOR CANNABINOIDS USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 74 BENZODIAZEPINES... 74 MARKET OVERVIEW... 75 MARKET REVENUE... 75 TABLE 44 WORLDWIDE MARKET FOR BENZODIAZEPINES USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 76
FIGURE 14 WORLDWIDE MARKET FOR BENZODIAZEPINES USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 76 ANTICHOLINERGICS... 76 MARKET OVERVIEW... 77 MARKET REVENUE... 77 TABLE 45 WORLDWIDE MARKET FOR ANTICHOLINERGICS USED AS ANTIEMETICS BY REGION, THROUGH 2015 ($ MILLIONS)... 77 FIGURE 15 WORLDWIDE MARKET FOR ANTICHOLINERGIC USED AS ANTIEMETICS BY REGION, 2008-2015 ($ MILLIONS)... 78 MARKET SHARES... 78 TABLE 46 WORLDWIDE ANTIEMETICS AGENTS MARKET SHARES BY REGION, 2009 (%)... 78 FIGURE 16 WORLDWIDE ANTIEMETICS AGENTS MARKET SHARES BY REGION, 2009 (%)... 79 CHAPTER NINE: MARKET BY APPLICATIONS... 80 MARKET SHARE OF APPLICATIONS... 80 TABLE 47 WORLDWIDE ANTIEMETIC MARKET SHARES, BY APPLICATION, 2009 (%)... 81 FIGURE 17 WORLDWIDE ANTIEMETICS MARKET SHARES, BY APPLICATION, 2009 (%)... 81 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV)... 81 CHEMOTHERAPY-INDUCED NAUSEA (CONTINUED)... 82 TABLE 48 ANTIMETIC THERAPIES FOR CHEMOTHERAPY- INDUCED NAUSEA AND VOMITING... 83 MARKET REVENUE... 83 TABLE 49 GLOBAL SALES OF ANTIEMETIC DRUGS IN CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING, THROUGH 2015 ($ MILLIONS)... 84 FIGURE 18 GLOBAL SALES OF ANTIEMETIC DRUGS IN CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING, 2008-2015 ($ MILLIONS)... 84 NAUSEA AND VOMITING DUE TO MOTION SICKNESS... 85 TABLE 50 ANTIEMETIC THERAPIES FOR NAUSEA AND VOMITING DUE TO MOTION SICKNESS... 85 MARKET REVENUE... 86 TABLE 51 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN MOTION SICKNESS, THROUGH 2015 ($ MILLIONS)... 86 FIGURE 19 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN MOTION SICKNESS, 2008-2015 ($ MILLIONS)... 86 POSTOPERATIVE NAUSEA AND VOMITING... 87 TABLE 52 ANTIEMETIC THERAPIES FOR POSTOPERATIVE NAUSEA AND VOMITING... 87 MARKET REVENUE... 87
TABLE 53 GLOBAL SALES OF ANTIEMETIC DRUGS IN POSTOPERATIVE NAUSEA AND VOMITING, THROUGH 2015 ($ MILLIONS)... 88 FIGURE 20 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN POSTOPERATIVE NAUSEA AND VOMITING, THROUGH 2015 ($ MILLIONS)... 88 POST-RADIATION NAUSEA AND VOMITING... 88 TABLE 54 ANTIEMETIC THERAPIES FOR RADIOTHERAPY INDUCED NAUSEA AND VOMITING... 89 MARKET REVENUE... 90 TABLE 55 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN RADIOTHERAPY-INDUCED NAUSEA AND VOMITING, THROUGH 2015 ($ MILLIONS)... 90 FIGURE 21 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN RADIOTHERAPY INDUCED NAUSEA AND VOMITING, 2008-2015 ($ MILLIONS)... 91 ACUTE GASTROENTERITIS... 91 TABLE 56 ANTIEMETIC THERAPIES FOR ACUTE GASTROENTRITIES VOMITING... 92 MARKET REVENUE... 92 TABLE 57 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN ACUTE GASTROENTRITIS, THROUGH 2015 ($ MILLIONS)... 92 FIGURE 22 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN ACUTE GASTROENTRITIS, 2008-2015 ($ MILLIONS)... 93 OTHER CONDITIONS... 93 TABLE 58 ANTIEMETIC THERAPIES FOR OTHER CONDITIONS... 94 MARKET REVENUE... 94 TABLE 59 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN OTHER CONDITIONS, THROUGH 2015 ($ MILLIONS)... 94 FIGURE 23 GLOBAL SALES OF ANTIEMETIC DRUGS USED IN OTHER CONDITIONS, THROUGH 2015 ($ MILLIONS)... 95 CHAPTER TEN: PATENT ANALYSIS... 96 PATENTS BY YEAR... 96 TABLE 60 NUMBER OF SIGNIFICANT ANTIEMETIC PATENTS BY YEAR, 2006 2010... 97 FIGURE 24 NUMBER OF ANTIEMETIC PATENTS BY YEAR, 2006 2010... 97 FIGURE 25 NUMBER OF ANTIEMETIC PATENTS BY YEAR, 2006 2010 (%)... 98 PATENTS BY MODE OF ADMINISTRATION... 98 TABLE 61 PATENTS BY MODE/ ROUTE OF ADMINISTRATION, 2006 2010... 98 FIGURE 26 PATENTS BY MODE/ OUTE OF ADMINISTRATION, 2006 2009... 99
PATENTS BY TYPE/CATEGORY... 99 TABLE 62 PATENTS BY TYPE/ CATEGORY FOR ANTIEMETICS, 2006 2010... 100 FIGURE 27 PATENTS BY TYPE/CATEGORY FOR ANTIEMETICS, 2006 2009... 101 PATENTS BY COMPANY... 101 TABLE 63 NUMBER OF U.S. PATENTS BY COMPANY FOR ANTIEMETICS, 2006 2010... 102 FIGURE 28 NUMBER OF U.S. PATENTS BY COMPANY FOR ANTIEMETICS, 2006 2010... 102 PATENTS BY COUNTRY... 103 TABLE 64 NUMBER OF U.S. PATENTS BY COUNTRY FOR ANTIEMETICS, 2006 2010... 103 FIGURE 29 NUMBER OF U.S. PATENTS BY COUNTRY FOR CONTRAST AGENTS, 2006 2010... 103 TABLE 65 PATENT SHARES BY COUNTRY FOR ANTIEMETICS, 2006 2010 (%)... 104 FIGURE 30 PATENT SHARES BY COUNTRY FOR ANTIEMETICS, 2006 2010 (%)... 104 ANTIEMETICS PATENTS WORLDWIDE... 104 TABLE 66 NUMBER OF ANTIEMETIC PATENTS ISSUED BY DIFFERENT PATENT ORGANIZATIONS WORLDWIDE, 2006 2010... 105 FIGURE 31 ANTIEMETIC PATENTS ISSUED BY DIFFERENT PATENT ORGANIZATIONS WORLDWIDE, 2006 2010... 106 PATENTS BY ASSIGNEE (WORLDWIDE)... 106 TABLE 67 PATENTS BY ASSIGNEE (WORLDWIDE) FOR ANTIEMETICS, 2006 2010... 106 FIGURE 32 PATENTS BY ASSGINEE (WORLDWIDE) FOR ANTIEMETICS, 2006 2010... 107 CHAPTER ELEVEN: CURRENT SITUATION OF ANTIEMETICS MARKET... 108 MARKET RESTRAINTS... 108 COMPETITION... 108 COST OF THE DRUGS... 109 PATENTS EXPIRATIONS... 109 TABLE 68 PATENT EXPIRATIONS... 109 GROWTH FACTORS... 110 LIFE EXPECTANCY... 110 PATENT PROTECTION... 110 DRUGS PORTFOLIO MANAGEMENT... 110 FUTURE OF ANTIEMETICS MARKET... 110 TABLE 69 COMPARISON OF I AND II GENERATION 5-HT3 RECEPTOR ANTAGONISTS... 111
CHAPTER TWELVE: COMPANY PROFILES... 112 ABBOTT LABS... 112 ACTAVIS... 113 AKORN, INC. AND AKORN STRIDES... 113 APOTEX INC.... 114 APP PHARMACEUTICALS... 114 ASTELLAS PHARMA GMBH... 115 AUROBINDO PHARMA... 115 BAXTER HEALTHCARE CORPORATION... 116 BEDFORD LABORATORIES... 117 BIOVAIL PHARMACEUTICALS, INC.... 117 CADILA PHARMACEUTICALS LTD.... 118 CIPLA LTD.... 119 CLARIS LIFESCIENCES... 119 CORE PHARMA LLC... 120 CYPRESS PHARMACEUTICAL, INC.... 120 DR. REDDY S LABORATORIES LTD.... 121 EISAI INC.... 122 GLAND PHARMA LTD... 122 GLAXO SMITHKLINE... 123 GLENMARK GENERICS LIMITED... 124 GROUP TECHNICALE-FARMOZ S.A... 124 G & W LABS... 125 HAMELN PHARMACEUTICALS LTD.... 125 HAWTHORN PHARMACEUTICALS, INC.... 126 HELSINN HEALTHCARE SA/EISAI... 126 HETERO DRUGS LIMITED... 127 HIKMA FARMACEUTICA PLC... 127 HOSPIRA... 128 IMPAX LABS... 128 INSIGHT PHARMACEUTICALS CORP.... 129 IPCA LABS LTD.... 130 JANSSEN (A DIVISION OF ORTHO MCNEIL JANSSEN, J & J)... 130 KING PHARMACEUTICALS INC.... 131 KVK-TECH, INC.... 132 LUITPOLD PHARMACEUTICALS, INC.... 132 MANX PHARMA LTD.... 133 MEDA PHARMACEUTICALS... 134 MERCK & CO., INC.... 134 MYLAN... 135 NOVARTIS PHARMACEUTICALS AUSTRALIA PTY LTD.... 136 NOVELL PHARMACEUTICAL LABORATORIES... 136 PAR PHARMACEUTICALS... 137 PFIZER INC.... 138
PIRAMAL HEALTHCARE LIMITED... 138 PLIVA HRVATSKA DOO (TEVA GROUP COMPANY)... 139 PROSTRAKAN GROUP PLC... 139 ROCHE LABORATORIES (F. HOFFMANN-LA ROCHE AG)... 140 ROSEMONT PHARMACEUTICALS LTD.... 141 SALIX PHARMACEUTICALS INC.... 142 SANOFI AVENTIS US... 142 SATO PHARMACEUTICALS... 143 SCHWARZ PHARMA (UCB SUBSIDIARY)... 144 SOLVAY PHARMACEUTICALS (UNIMED/ABBOTT)... 144 STRATIVA PHARMACEUTICALS... 145 SUN PHARMACEUTICAL INDUSTRIES LTD.... 145 TARO PHARMACEUTICAL INDUSTRIES LTD.... 146 TEVA PHARMACEUTICAL INDUSTRIES LTD.... 146 TORRENT PHARMACEUTICALS... 147 WALLACE PHARMACEUTICALS LTD.... 148 WATSON PHARMACEUTICALS, INC.... 148 WOCKHARDT USA LLC... 149 ZYDUS CADILA... 149 ZYDUS PHARMS USA... 150 CHAPTER THIRTEEN: ABBREVIATIONS... 151 TABLE 70 ABBREVIATIONS... 151 TABLE 70 (CONTINUED)... 152 TABLE 70 (CONTINUED)... 153