Phase I clinical trials

Phase I trials are conducted to find a dose to use in subsequent trials. They provide data on the rate of adverse events at different dose levels and provide data for studying the pharmacokinetics and pharmacology of the drug. Dose-finding studies that involve therapies with little or no toxicity often enroll healthy volunteers and usually have a control group. Trials in oncology and other life threatening diseases such as HIV enroll patients because treatments are usually highly toxic and to enroll healthy volunteers would not be ethical. The primary outcome for phase I trials in oncology and HIV is typically dose limiting toxicity. Such studies require different design strategies. In section 1.2, we review dose-finding procedures used in healthy volunteers. In Section 1.3 we describe dose-finding procedures for trials with toxic outcomes enrolling patients. In Section 1.4, we list some other design problems in dose-finding.