ADVERSE EVENTS AND DISCOMFORT IN STUDIES IN HEALTHY-SUBJECTS - THE VOLUNTEERS PERSPECTIVE - A SURVEY CONDUCTED BY THE GERMAN-ASSOCIATION-FOR-APPLIED-HUMAN-PHARMACOLOGY

Objective: The various good clinical practice (GCP) guidelines do not define the volunteering subject as an active party. The present survey addresses the volunteer's perception of study-related inconvenience a nd risk and its impact on their decision to enrol. Methods: The survey consisted of a questionnaire to be filled out voluntarily and anonymo usly by healthy subjects who volunteered for enrolment in human pharma cology studies and who had participated in at least one previous study . Twenty-five categorised multiple-choice questions covered previous s tudy experience, motives for volunteering, perception of and complianc e with study directives and restrictions, past experience with adverse events, impact of the study environment on perceived well-being and t he nature of adverse events likely to discourage them from enrolment. Results: Seven centres contributed by providing at least 30 (range 30- 100) evaluable questionnaires. The database consists of a total of 440 healthy subjects (30.5% females, 69.5% males), from 18 to over 60 yea rs of age. Two hundred and seven subjects (47.1%) were company employe es and 233 (52.9%) were external volunteers. Eighty nine percent only participated in studies at one particular centre. Some 53.3% indicated financial motives, 27.8% 'contribution to an improvement of pharmacot herapy', 12.7% 'social responsibility', while 6.2% indicated other mot ives, mainly the opportunity of a free medical check-up. Thirteen subj ects (3%) admitted to not answering correctly to the recruitment quest ions; this limited reliability is suspected to be even larger when the answer might preclude enrolment. From the volunteers' perspective, th e environmental study conditions clearly appeared to have a highly rel evant impact on their personal well-being. Some 17.1% of the subjects reported to have suffered adverse events occasionally and 2.7% frequen tly; but 14% admitted not reporting adverse events promptly and about 20% indicated that, with respect to previous adverse events, they firs t sought advice from other volunteers rather than from the investigato r. Conclusions: Adverse events and inconveniences are inherent to nont herapeutic studies in healthy subjects. From the volunteer's perspecti ve it appears that the incidence of adverse experiences in such studie s exceeds the reported frequencies from investigators considerably. Th is finding suggests that investigators are usually not aware or able t o ascertain the true incidence of adverse events. The present survey a lso confirms that pertinent information on the personal history may be unreliable. Volunteers are reluctant to answer questions regarding, i ll particular, their smoking habits, caffeine and alcohol consumption. Regarding the matter of informed consent, a noteworthy contradiction between the volunteers' attitude and behaviour became apparent. Althou gh the volunteers admit that even rather minor adverse events ordinari ly would discourage them, they still consent to enrolment. In view of this apparent contradiction, there is no alternative to the investigat or's personal responsibility to counsel and protect the subject. Surve ys such as this one may contribute to the awareness that the explicitn ess of GCP guidelines merely define the format, but not the content qu ality of these fundamental ethical values, which remain the unique bur den and challenge of the investigator.