The problem of measurement error in multisite clinical trials

Area of Science:

• Clinical Psychopharmacology
• Psychometric Measurement
• Clinical Trial Methodology

Background:

• Multisite randomized clinical trials require significant participant commitment and resources.
• Methodological challenges, particularly measurement error, can lead to uninterpretable results in complex trials.
• Addressing these challenges is crucial for advancing industry-sponsored psychopharmacologic drug development.

Purpose of the Study:

• To describe the outcome of interrater reliability training for the Hamilton Depression Rating Scale (HDRS).
• To assess the magnitude of measurement error in a multisite clinical trial setting.
• To provide preliminary evidence on the impact of measurement error on detecting clinical change.

Main Methods:

• Conducted intensive interrater reliability training sessions for the 17-item Hamilton Depression Rating Scale.
• Training occurred at the commencement of a Phase II multisite clinical drug trial.
• Data were collected to evaluate the consistency of HDRS ratings among different raters.

Main Results:

• The training sessions underscored a substantial degree of error in HDRS ratings within the trial setting.
• Preliminary data suggest that this measurement error may significantly affect the ability to detect clinical changes.
• Variability in rating can obscure true treatment effects.

Conclusions:

• Interrater reliability is a critical factor in the validity of psychopharmacologic clinical trials.
• Intensive, ongoing rater training is essential to minimize measurement error.
• Failure to address measurement error can jeopardize the interpretability and success of clinical trials.