The role of reference intervals of laboratory tests in early phase clinical research in healthy volunteers

Abstract

This article discusses one of the most disputable issues in national clinical research practice in healthy volunteers. Regulatory requirements forbid to assess even minor deviations of laboratory parameters from reference intervals as not clinically significant. Authors made analysis of such requirements from positions of foreign and national guidelines of early phase clinical research and with regard to their own experience in the field. As an important part of this work, retrospective analysis of the laboratory test results data of healthy volunteers taken from several clinical trials was conducted. The aim of this analysis was to establish the rate of not clinically significant deviations from reference intervals. The results of the analysis revealed rather high rate of not clinically significant deviations of some laboratory parameters from reference intervals in volunteers with confirmed status “healthy”. Authors noted that developers of clinical trial protocols have no unified approach to generate list of necessary laboratory tests and methods of assessment of the results. Ethical and financial aspects of the problem under discussion are also touched in this article. In conclusion, authors suggest the scale of clinical significance assessment of deviations of basic laboratory parameters from reference intervals as one of the possible options of optimizing current regulatory requirements.

Keywords

• клинические исследования ранних фаз
• биоэквивалентность
• здоровые добровольцы
• референтный интервал
• лабораторные показатели