Reliability of symptom reports by healthy volunteers treated with placebo over several time periods

In four test periods (medication-free control, three placebo periods with t he suggestion randomised placebo or sedative or stimulant) 78 healthy medic al students had to check off on a side-effect questionnaire those symptoms that they had experienced over the previous 72 h (adverse nondrug reactions ). In the control period only 14 volunteers (18 %) were without symptoms. I n the course of 4 weeks this number doubled, and the number of symptoms com plained decreased correspondingly, e.g. tiredness, headaches, muscle and jo int pains etc. This development is relevant inasmuch as in phase-I studies the well-being of the volunteers is often monitored over protracted periods of time and perhaps decreasing interest or a decreasing motivation must be reckoned with. One or two rounds of tests present special situations, in a ny case, which cannot be reproduced. As the frequency of the symptoms compl ained of is modified by the personality structure, balanced groups must be formed for controlled studies. In Phase I trials it may sometimes be useful to characterize the volunteers psychologically.