| Contents | 6 |
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| Contributors | 8 |
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| Introduction | 10 |
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| Why a Book About Clinical Trials in Rheumatoid Arthritis and Osteoarthritis? | 10 |
| How This Book Works | 11 |
| References | 12 |
| Historical and Current Perspectives on Management of Osteoarthritis and Rheumatoid Arthritis | 14 |
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| Historical and Current Perspectives on Management of Osteoarthritis | 14 |
| Historical Aspects | 15 |
| Predisposing Factors | 15 |
| Pathogenesis | 15 |
| Treatment of OA | 16 |
| Nonpharmacological Therapies | 16 |
| Pharmacological Therapy | 16 |
| Surgical Treatments | 20 |
| Summary | 21 |
| Historical and Current Perspectives on Management of Rheumatoid Arthritis | 21 |
| Evolutional History of Pharmacotherapeutics in RA | 22 |
| Initial Assessment of Patients with RA | 24 |
| Further Management of RA Patients | 24 |
| Nonpharmacological Treatment of RA | 25 |
| Pharmacological Treatment of RA | 26 |
| Surgical Treatment of RA | 34 |
| Summary | 35 |
| References | 35 |
| Development of Biological Therapies for Inflammatory Arthritis | 46 |
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| Tumor Necrosis Factor- | 46 |
| for Rheumatoid Arthritis | 46 |
| Ankylosing Spondylitis | 48 |
| Psoriatic Arthritis | 49 |
| Juvenile Idiopathic Arthritis | 49 |
| Safety Considerations | 49 |
| Economic Considerations | 50 |
| The Future | 51 |
| Other Biological Agents | 51 |
| References | 56 |
| Study Design and End Points for Rheumatoid Arthritis Trials | 60 |
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| Introduction | 60 |
| Patient Selection | 64 |
| Types of Clinical Trials | 65 |
| End Points | 67 |
| Single End Points | 68 |
| Composite Measures | 71 |
| Adverse Events | 75 |
| Conclusion | 75 |
| References | 76 |
| Study Design and End Points in Ankylosing Spondylitis Clinical Trials | 78 |
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| Introduction | 78 |
| Study Design | 78 |
| Scope of Patients | 81 |
| Type of End Points to Consider | 82 |
| Instruments for Various End Points | 83 |
| Assessment of Response/Improvement | 86 |
| Conclusion | 87 |
| References | 87 |
| Trial Design and Outcomes in Osteoarthritis | 90 |
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| Introduction | 90 |
| Study Design | 90 |
| Scientific versus Pragmatic Trials | 91 |
| Study Duration | 92 |
| Patient Selection | 92 |
| Control Arm | 93 |
| Sample Size | 95 |
| Outcome Assessment | 95 |
| Compliance | 97 |
| Statistics | 97 |
| Presentation and Dissemination | 98 |
| Study Organization | 98 |
| Conclusion | 98 |
| References | 99 |
| Ethical Considerations | 100 |
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| Introduction | 100 |
| Who Does What? | 101 |
| Sponsorship: Who’s Paying the Bill? | 101 |
| Placebo or Not Placebo? | 102 |
| Randomization | 103 |
| Who Can Take Part? | 104 |
| Trial Procedures | 105 |
| Ethical Review | 109 |
| Informed Consent | 111 |
| Dissemination | 113 |
| Conclusion | 113 |
| References | 113 |
| Appendix 1 | 115 |
| What Is the Purpose of the Study? | 115 |
| Why Have I Been Chosen? | 115 |
| Do I Have to Take Part? | 115 |
| What Will Happen to Me if I Take Part? | 115 |
| What Do I Have to Do? | 116 |
| What Is the Drug That Is Being Tested? | 117 |
| What Are the Alternatives for Treatment? | 117 |
| What Are the Side Effects of Taking Part? | 117 |
| What Are the Possible Disadvantages and Risks of Taking Part? | 117 |
| What Are the Possible Benefits of Taking Part? | 117 |
| What if the New Information Becomes Available? | 118 |
| What Happens When the Research Study Stops? | 118 |
| What if Something Goes Wrong? | 118 |
| Will My Taking Part in This Study Be Kept Confidential? | 118 |
| What Will Happen to the Results of the Research Study? | 119 |
| Who Is Organizing and Funding the Research? | 119 |
| Contact for Further Information | 119 |
| Appendix 2 | 120 |
| Organization of the Clinical Trial by the Sponsor | 122 |
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| Introduction | 122 |
| Regulatory Guidance | 122 |
| Surrogate Markers | 123 |
| Couriers | 125 |
| Investigator Meetings | 125 |
| Cross-Calibration of Scanners | 126 |
| Inclusion and Exclusion Criteria | 127 |
| Data Flow | 127 |
| The Data Monitoring Committee | 128 |
| Trial Audit | 129 |
| Trial Closure | 130 |
| Conclusion | 130 |
| References | 130 |
| Organization of the Trial at the Investigator Site | 132 |
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| Introduction | 132 |
| Site Resources | 133 |
| Study Budget and Clinical Trial Agreement | 134 |
| Ethics IRB and Informed Consent | 135 |
| Study Initiation and Conduct | 136 |
| Handling of Blood Samples: Central versus Local Laboratories | 137 |
| Pharmacy | 138 |
| Recruitment Methods | 138 |
| Monitoring Adverse Events | 139 |
| Informed Consent | 140 |
| Subject Retention and Compliance | 141 |
| Advocacy | 141 |
| Study Closeout | 142 |
| Conclusion | 142 |
| References | 143 |
| Role of the Imaging Core Laboratory in Rheumatoid Arthritis and Osteoarthritis Clinical Trials | 144 |
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| Introduction | 144 |
| The Imaging Core Laboratory | 144 |
| Conclusion | 158 |
| References | 158 |
| Biochemical Markers of Rheumatoid Arthritis and Osteoarthritis: Clinical U
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