Effect and Defining Optimal Dose

Characterization of the dose-effect relationship is an important component of clinical trials performed during the initial stages of clinical drug development. These early trials frequently follow a dose-escalation design in which increasing dose levels of drug are 

TABLE 18.2 Comparison of Recommended Doses for Antihypeitensive Agents Based on Initial Dose-Finding Clinical Trials and Subsequent Experience in Randomized Clinical Trials and Clinical Practice  

Drug Dose range (mg) Early studies Present dose Lowest effective dose (mg) 

FIGURE 18.14 Dose intensity meta-analysis for doxorubicin in patients with osteosarcoma. Each bubble represents a separate clinical trial and the size of the bubble is proportional to the number of patients treated during the trial. Doxorubicin was administered prior to definitive surgical resection and effect is 90% necrosis of tumor in the resected specimen. Dose intensity or dose rate is measured in mg/m /week. (Reproduced with permission from Smith MA, Ungerleider RS, Horowitz ME, Simon R. J Natl Cancer Inst 1991 83 1460-70.) 

A dose intensity analysis such as this one is useful in defining the optimal dose of an anticancer drug if a relationship between dose and therapeutic effect is observed. 

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