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VOLUME 69 NUMBER 3 MARCH 2001 novel therapies. 3 In the initial investigations of therapeutic candidates in humans, biomarkers can provide a basis for the selection of lead compounds for phase 3 clinical trials. 3-5 Biomarkers contribute knowledge about clinical pharmacology and provide a basis for the designing of clinical trials that expeditiously and definitively evaluate safety and efficacy. Biomarkers provide information for guidance in dosing and minimize interindividual variation in response. For example, rapid clearance of 99mTc-sestamibi, a substrate for P-glycoprotein that is associated with multidrug resistance, has been shown to predict lack of tumor response to adjuvant chemotherapy in some forms of breast cancer. 6 Biomarkers that represent highly sensitive and specific indicators of disease pathways have been used as substitutes for outcomes in clinical trials when evidence indicates that they …