Objective: Participants in a phase I study were interviewed in order to establish the incidence and variability of subjective symptoms and changes in quality of life during phase I trials.
Methods: The healthy subjects were randomized to receive a single dose of either 0.5 mg digoxin or an equivalent amount of each of four digitaloid mixtures every 14 days. The trial involved five 24-h monitoring periods. The duration of the study was 57 days. Wellbeing, subjective symptoms and quality of life were measured before, during and after the trial using the Freiburg Symptoms List (FSL), Wellbeing Scales (WBS), and Life Satisfaction Questionnaire (LSQ).
Results: Eight healthy subjects (25 years) were enrolled in the study. Their subjective symptoms were below the reference values for healthy subjects for each test but above the theoretical minimum and maximum values for total wellbeing, indicating that healthy subjects-not just patients-display subjective symptoms and impairment of wellbeing to a greater or lesser extent prior to a clinical trial. In terms of the total study population, comparison of the questionnaire scores before, during and after the study disclosed no significant changes in wellbeing or quality of life. However, some participants displayed marked intraindividual fluctuation.
Conclusions: A careful exploration of the baseline symptoms is necessary even in healthy subjects to avoid observation bias. The symptom course differs greatly from individual to individual; therefore in a phase I study only group scores of wellbeing should be used to assess the possible effects of trial-related factors. A setting like the one used in our study does not impair the quality of life of healthy subjects and as such can be regarded as a fairly neutral means of measuring wellbeing.