When should factorial designs be used for late-phase randomised controlled trials?

Area of Science:

• Clinical trial design
• Medical research methodology
• Statistical analysis in healthcare

Background:

• Factorial designs evaluate multiple interventions simultaneously (e.g., 2x2 designs).
• These designs can be more resource-efficient than traditional randomized controlled trials.
• Despite benefits, factorial designs are underutilized in late-phase clinical research.

Purpose of the Study:

• To identify and discuss critical issues for implementing factorial randomized controlled trials.
• To encourage wider adoption of factorial designs by addressing potential challenges.
• To provide guidance for investigators considering this design in late-phase settings.

Main Methods:

• A systematic survey of journal articles on factorial randomized controlled trials published between 2000 and 2022.
• Analysis of identified issues based on literature review and expert experience.
• Categorization of issues into clinical, practical, statistical, and external factors.

Main Results:

• Identified 15 key issues favoring factorial designs, including ease of co-administration, low interaction risk, and similar eligibility criteria.
• Practical advantages include unaffected recruitment and adherence, and simplified blinding.
• Statistical benefits include suitable analysis scales and no need for multiplicity adjustment; designs can reduce sample size requirements.

Conclusions:

• Factorial designs are underutilized and should be more frequently considered in clinical research.
• Successful implementation hinges on careful consideration of identified clinical, practical, statistical, and external factors.
• A low potential for interaction effects between interventions is a crucial prerequisite for optimal use.