Clinical development of dietary supplements: The perils of starting at phase III

Dietary supplements are in worldwide use particularly for diseases for which conventional agents are ineffective. Many of the diseases have subjective endpoints and variable natural histories which lead to large placebo effects. Phase III studies with their large resource requirements should not be undertaken until the commonly used dose of the dietary supplement has been evaluated vs placebo, and if necessary raised until specific efficacy is demonstrated, in phase II testing. If phase II tests precede phase III evaluation, a product destined to fail will not consume important resources, and the optimum dose of products destined to succeed can be identified.

Graphical AbstractIdealized results of low, medium, and high doses of an agent against placebo. Phase II placebo-controlled trials are recommended to find a dose Y with specific efficacy compared to placebo.Figure optionsDownload full-size imageDownload as PowerPoint slide