Overview of periodontal clinical trials utilizing anti-infective or host modulating agents.

Issues in periodontal trials designed to evaluate anti-infective or host modulating agents for the prevention and treatment of periodontal diseases are reviewed in this paper. Clinical trial designs, prevention versus treatment, disease activity, utility of new measurement technologies, ethical and safety issues, selection of outcome variables, and clinical significance are discussed. In general, randomized parallel arm, double-blinded, controlled clinical trials are most appropriate for testing anti-infective and host modulating agents. New measurement technologies may offer increased measurement resolution and automated data capture; but, depending on their specific application and level of examiner reproducibility, these technologies may or may not result in lowered thresholds for declaring change. Mechanical therapy for common plaque-associated gingivitis and adult periodontitis is effective, has low risk, and is widely accepted as a minimum standard of care. New agents for treatment of these diseases must carry minimal risk and have equal or greater effectiveness than this standard of care. Outcome variables for gingivitis trials should include a visual index of gingival inflammation and a separate or component index of gingival bleeding. Prevention studies of periodontitis require a longer duration than treatment studies. Maintenance of mean clinical attachment level should be a primary outcome measure for all prevention studies of adult periodontitis. Maintenance of alveolar bone support is an essential additional outcome for agents specifically acting on bone. The design and conduct of clinical trials for anti-infective and host modulating agents depend on the specific hypothesis to be tested and the ethical demands of providing safe and effective care for all study volunteers.