Subject(s)
Colitis, Ulcerative , Aminosalicylic Acids/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Biological Products/therapeutic use , Breast Feeding , Colectomy , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/etiology , Colitis, Ulcerative/therapy , Colorectal Neoplasms/prevention & control , Cyclosporine/therapeutic use , Early Detection of Cancer , Female , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Osteoporosis/etiology , Patient Education as Topic , Pregnancy , Pregnancy Complications/etiology , Remission Induction/methods , Thionucleosides/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
Treatment of inflammatory bowel disease has greatly improved with the development of targeted, monoclonal antibody-based therapies. Tumor necrosis factor antagonists are frequently used to treat patients with Crohn's disease or ulcerative colitis, but they have side effects and their efficacy often decreases with use. New, more effective drugs are therefore needed and in development. However, many agents that appeared to be promising in preclinical studies have failed to show efficacy in clinical trials. We discuss possible reasons for the failures of these reagents in trials, which include the high rate of response to placebo, an inadequate range of doses, inappropriate timing of end point measurements, the changing therapeutic environment, and the competitive trial system. We also review regulatory guidelines for end points and trial design and recommend ways to improve trials.
Subject(s)
Inflammatory Bowel Diseases/drug therapy , Randomized Controlled Trials as Topic/standards , Research Design/standards , Statistics as Topic/standards , Antibodies, Monoclonal/therapeutic use , Endpoint Determination , Humans , Randomized Controlled Trials as Topic/trends , Research Design/trends , Statistics as Topic/trends , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
The management of Crohn's disease is rapidly changing. The advent of potent immunomodulatory and biologic therapies has led to more demanding endpoints for clinical trials than only clinical response and remission. Complete withdrawal of corticosteroids, healing of endoscopically visible lesions, and prevention of structural damage are only a few new endpoints that are finding their way into the clinical trials of today and those that are being developed for the future. Given the importance of selecting the most appropriate and relevant endpoints, the International Organization for Inflammatory Bowel Diseases (IOIBD) decided to develop guidelines that could be used by individual researchers, the pharmaceutical industry, and the regulatory bodies. The current document is to be read as a "position paper," which is the result of several years of discussion and consensus finding that was finally approved by the entire membership of the group. The proposed instruments will need further validation and standardization to demonstrate that they are reliable in stable disease and responsive to change, and to determine the cutoff points for response and remission.
