Designs with Randomization Following Initial Study Treatment

Abstract

Abstract Clinical study designs with randomization after the initial study treatment have been used in diverse disease areas such as arrhythmia, Alzheimer's disease, schizophrenia, migraine, headache, cancer, acquired immunodeficiency syndrome, and irritable bowel syndrome. They are useful in situations where the placebo‐controlled parallel group trial would be difficult to perform, such as in the investigation of long‐term efficacy of a drug when long‐term placebo treatment is not feasible, to address specific scientific questions, or to evaluate complex treatment schemes. Clinical studies with randomization after the initial study treatment are conducted in at least two stages. In the first stage, patients might either commence with a single treatment in an open‐label fashion, or they might be randomized to several treatments, possibly including a control. A treatment‐free interval might follow. Depending on the scientific question addressed by the trial, entry in the second trial stage might depend on the patient's benefit from the initial treatment. Further randomized trial stages can be added in the same fashion. The application of the approach will be discussed in detail for randomized withdrawal designs, randomized delayed start designs, and randomized retreatment designs.