Adverse nondrug reactions: an update

Area of Science:

• Clinical Pharmacology
• Psychology

Background:

• Stage I clinical trials involve healthy volunteers, necessitating a thorough characterization of these subjects.
• Complaints in volunteers can mimic drug side effects but may arise from non-drug reactions.
• Understanding the link between subject characteristics and symptom reporting is crucial for trial integrity.

Purpose of the Study:

• To investigate the relationship between personality, motivation, and emotional state and the incidence of complaints in healthy volunteers.
• To determine if reported symptoms in drug-naive subjects correlate with psychological factors.

Main Methods:

• One hundred thirty medical students participated in the study.
• Participants completed the "Questionnaire for Side Effects of Drugs".
• Psychological assessments included the Freiburg Personality Inventory, Motivation Q-Sort, and State-Trait-Anxiety Inventory.

Main Results:

• Common complaints in drug-naive volunteers were fatigue (65%), headache (25%), and nasal congestion (30%).
• A significant minority of students (89%) reported at least one symptom.
• Weak but significant correlations were found between symptom count and nervousness, neuroticism, motivation, and trait-anxiety.
• Cluster analysis identified two distinct groups: one with fewer complaints (less anxious, stable, success-motivated) and another with more frequent complaints.

Conclusions:

• The incidence of complaints in healthy volunteers is not random and is influenced by psychological factors.
• These findings have significant implications for the interpretation of results in Stage I clinical trials.
• Subject characteristics should be considered when evaluating adverse events in early-phase drug development.