Making Sense of Biostatistics: Therapeutic Confirmatory Trials

Following the completion of Phase I trials, an investigational drug can move into Phase II trials, also known as therapeutic exploratory trials. As described in ICH Guidance E8: General Considerations for Clinical Trials, Phase II trials explore the use of a drug for its intended therapeutic indication by employing around 100-300 participants with the medical condition of concern. For example, an investigational antihypertensive drug would be given to participants with high blood pressure. Phase II trials, which are generally relatively short in duration, provide an initial estimate of the drug’s safety and efficacy. Moreover, they provide useful information in preparation for Phase III trials, or therapeutic confirmatory trials. This information includes an estimation of the most appropriate dosage(s), determination of the relevant endpoint(s), and other elements of study design, experimental methodology, and statistical analysis (Turner). Phase III therapeutic confirmatory trials typically involve around 3,000-5,000 participants with the medical condition of concern. (This number can be much smaller when studying a drug for a rare condition.) Phase III trials are typically longer in duration than Phase II trials. They are comparative in nature, so participants are randomized to a drug treatmen