ABSTRACT
In clinical research, it is of particular interest to clinicians to identify patients with disease targets under study, who are most likely to respond to the test treatment under investigation. In practice, an enrichment process is often employed to identify such a target patient population. Clinical trials utilizing an enrichment design are referred to as target clinical trials. As indicated by several authors, after completion of the human genome project, the disease targets at certain molecular level can be identified and should be utilized for treatment of diseases (see, e.g., Maitournam and Simon, 2005; Casciano and Woodcock, 2006). As a result, diagnostic devices for detection of diseases using biotechnology such microarray, polymerase chain reaction (PCR), mRNA transcript profiling, and others become possible in practice (FDA, 2005a, 2005b, 2007). The treatments specific for the molecular targets could then be developed for those patients who are most likely to benefit. Consequently, personalized medicine could become a reality. A typical example is the clinical development of Herceptin (trastuzumab), which is targeted at the patients with metastatic breast cancer with an over-expression of HER2 (human epidermal growth factor receptor) protein. We will refer to these treatments as the target treatments or drugs. Development of target treatments involves translation from the accuracy and precision of diagnostic devices for the molecular targets to the effectiveness and safety of the treatment modality for the patient population with the targets. Therefore, evaluation of target treatments is much more complicated than that of the traditional drugs. To address the issues of development of the targeted drugs, in April 2005, the U.S. FDA Drug-Diagnostic Co-development Concept Paper.
