SUBJECTIVE SYMPTOMS AND QUALITY-OF-LIFE IN HEALTHY-SUBJECTS DURING A PHASE-I STUDY

Objective: Participants in a phase I study were interviewed in order t o establish the incidence and variability of subjective symptoms and c hanges in quality of life during phase I trials. Methods: The healthy subjects were randomized to receive a single dose of either 0.5 mg dig oxin or an equivalent amount of each of four digitaloid mixtures every 14 days. The trial involved five 24-h monitoring periods. The duratio n of the study was 57 days. Wellbeing, subjective symptoms and quality of life were measured before, during and after the trial using the Fr eiburg Symptoms List (FSL), Wellbeing Scales (WBS), and Life Satisfact ion Questionnaire (LSQ). Results: Eight healthy subjects (25 years) we re enrolled in the study. Their subjective symptoms were below the ref erence values for healthy subjects for each test but above the theoret ical minimum and maximum values for total wellbeing, indicating that h ealthy subjects - not just patients - display subjective symptoms and impairment of wellbeing to a greater or lesser extent prior to a clini cal trial. In terms of the total study population, comparison of the q uestionnaire scores before, during and after the study disclosed no si gnificant changes in wellbeing or quality of life. However, some parti cipants displayed marked intraindividual fluctuation. Conclusions: A c areful exploration of the baseline symptoms is necessary even in healt hy subjects to avoid observation bias. The symptom course differs grea tly from individual to individual; therefore in a phase I study only g roup scores of wellbeing should be used to assess the possible effects of trial-related factors. A set ting like the one used in our study d oes not impair the quality of life of healthy subjects and as such can be regarded as a fairly neutral means of measuring well-being.