Abstract

SCIENTIFIC FACTORS ON MICRODOSING APPROACH IN PHARMACEUTICAL DEVELOPMENT

Shein-Chung Chow and Fuyu Song*

Abstract

In recent years, microdosing approach has received much attention in pharmaceutical research and development. The concept of microdosing approach focuses on safety signal detection, which is primarily for exploratory purpose (FDA, 2006; ICH, 2009).[2,4] Burt (2011)[3] indicated that the use of microdosing approach has great potential in shortening development by making critical go/no-go decision in early pharmaceutical development. In addition, it is believed that microdosing approach will increase the probability of success based on a limited number of subjects available. In practice, however, many scientific factors regarding the design and analysis of microdose studies are commonly encountered which have limited the potential use of microdosing approach in pharmaceutical development. These scientific factors and/or issues include, but are not limited to, (i) distinction between the effects due to microdose and placebo, (ii) microdose versus therapeutic dose, (iii) characterization of dose response curve, (iv) accuracy and reliability of predictive model, and (v) possible false positive and false negative rate. These issues are discussed. In addition, a predictive index is proposed to assess the accuracy and reliability of predictive model established based on data collected from a microdose study.

Keywords: Placebo effect; False positive; False negative; Predictive index.