Pre-Randomization Predictors of Study Discontinuation in a Preclinical Alzheimer's Disease Randomized Controlled...

Area of Science:

• Clinical Trials
• Neurodegenerative Diseases
• Alzheimer's Disease Prevention

Background:

• Participant discontinuation impacts clinical trial power, bias, and interpretability.
• Participant retention is crucial for trial success, akin to recruitment.

Purpose of the Study:

• Identify pre-randomization characteristics associated with premature discontinuation in the A4 Study.
• Inform strategies for participant selection and retention in preclinical Alzheimer's disease trials.

Main Methods:

• Analyzed 1169 participants from the A4 trial, classifying them as completers or dropouts.
• Used univariate and multivariable generalized linear mixed models (GLMM) to assess predictors of discontinuation.
• Included demographic, clinical, amyloid PET, and genetic factors as potential predictors.

Main Results:

• 29% of participants discontinued during the blinded phase.
• Higher screening State-Trait Anxiety Inventory (STAI) scores and older age predicted discontinuation.
• Family history of dementia and APOE ε4 carrier status were marginally associated with lower discontinuation rates.

Conclusions:

• Older age and higher baseline anxiety increase dropout risk in preclinical AD trials.
• Family history of dementia and APOE ε4 carriage may be protective factors against dropout.
• Findings aid in designing future trials to improve participant retention and study outcomes.