Control in the middle (CIM) for three-period crossover studies

Area of Science:

• Clinical Trials Methodology
• Biomedical Research Design

Background:

• Three-period crossover studies are efficient for Phase II clinical trials.
• The control-in-the-middle (CIM) design is an underutilized variation.
• CIM designs can address specific challenges in clinical research, such as lack of placebos.

Purpose of the Study:

• To propose rigorous control-in-the-middle (CIM) crossover designs for Phase II clinical trials.
• To demonstrate the utility of CIM designs in scenarios with no available placebo.
• To highlight CIM's value in comparing active treatments or assessing placebo effects.

Main Methods:

• The study proposes novel three-period crossover designs incorporating a central control phase.
• Designs are tailored for comparing two active treatments, testing a single active treatment without a placebo, or evaluating placebo effects.
• For trials lacking placebos, a deception strategy is outlined, subject to ethics committee approval.

Main Results:

• The proposed CIM designs offer efficient and convenient methods for Phase II clinical trials.
• These designs are particularly advantageous for herbal product studies where placebos may not be feasible.
• CIM facilitates the differentiation between behavioral and biological treatment effects.

Conclusions:

• The control-in-the-middle (CIM) crossover design is a valuable, rigorous addition to clinical trial methodology.
• This design can efficiently answer research questions in specific contexts, including those lacking placebos.
• Ethical considerations, such as informed consent and potential deception, are crucial for implementing CIM designs.