Selection of healthy volunteers for phase I studies

Abstract

Healthy volunteers selection is one of the foundations for phase I results. Safety for volunteers, quality of data and reliability for study results depend on healthy volunteers selection. The selection aim is not to choose normal subjects but to exclude every people with diseases or risk factors which could result in increased danger for themselves or confuse the interpretation of study results. The selection procedure needs to define a list of relevant disease to be excluded depending on phase I objectives (tolerability, pharmacokinetic, pharmacodynamic). The choice of diseases is based on frequency, potential risk for the subjects or for the study. The selection is mainly a clinical process but because of asymptomatic diseases a laboratory screening is necessary and useful. This laboratory screening requires that a basic common list of relevant tests be determined and an appropriate method of cut-off point determination based on an evaluation of the risk of disease. According to the drug or the objective of the study adaptation of the procedure must be carried out. The percentage of erroneous inclusion of subjects is the best validation criterion for selection. The use of such a selection methodology by the author's group in Lyon results in a 50% exclusion for 494 first seen subjects with only 1% erroneous inclusion and 6% exclusion for laboratory test anomalies.