Pharmacological management of childhood constipation: Bridging today’s gaps with tomorrow’s therapies

Table 4 Methods to control the placebo effect

Method	Description
Trial design	Rigorous randomization and concealment
	Careful selection of the placebo with matching taste, color, texture, and packaging
	Standardized co-interventions such as toilet training and education
	Bowel cleanout before randomization
Endpoint measurement	Encourage the use of sustained responses
	Use objective measurements (e.g., Bristol stool chart to assess stool consistency)
	Use electronic time-stamped diaries
Rescue therapy	Precise instructions and exact threshold for administration, with strict record maintenance
Data quality	Minimize missing data
Multicenter studies	Site training to ensure uniformity
	Monitor site-level placebo response
Statistical analysis	Mixed-effect models to minimize the amplification of the placebo effect
	Calculating adequate power to reduce placebo response
	Use sensitivity analysis for different responder thresholds