1. One good example of considering gene expressions at the review for approval Taxol: Indicated for the adjuvant treatment of node- positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. 1.retrospective subgroup analysis ER/PR (-): !!ER/PR (+): ?? ODAC: Retrospective analysis should not be used basis for approval. The indication should include all patients.

2. 2. Characteristics of subgroups divided by the results of genetic analyses could be different ODAC: Because receptor-positive tumors tend to grow more slowly, longer follow-up would be needed. 3. Patients’ options Representative of patients (ODAC): “I think patients need the options. --- For those who can’t tolerate to tamoxifen, it would be a very important option to be able to have Taxol.”

3. CONCLUSION retrospective The results is HYPOTHESIS That Clinical Trial = Confirmatory Study subgroup analyses CLINICAL TRIAL prospectively specified in the protocol gene/expression analyses Require Confirmatory Study Ethical Problems !? Reevaluate the outcome

4. Study Design How can we stratify? How can we perform statistical analyses? Is it possible to apply results of microarray method prospectively? How can we estimate the number of patients to be enrolled? Genetical Information (by microarray, etc.) Sufficient data obtained from clinical trials should be required (e.g. survival, response to drugs,natural course, etc.)