Clinical Trial

Drug Development Trials

Clinical trials in drug development follow from laboratory experiments, usually involving in vitro experiments or animal studies. The traditional goal of a preclinical study is to obtain preliminary information on pharmacology and toxicology. Before a new drug may be used in human subjects, several regulatory bodies, such as the internal review board (IRB), Food and Drug Administration (FDA), and data safety monitoring board, must formally approve the study. Clinical trials in drug development are conducted in a sequential fashion and categorized as Phase I, Phase II, Phase III, and Phase IV trial designs. The details of each phase of a clinical trial investigation are well defined within a document termed a clinical trial protocol. The FDA provides recommendations for the structure of Phase I through III trials in several disease areas.

Phase I trials consist primarily of healthy volunteer and participant studies. The primary objective of a Phase I trial is to determine the maximum tolerated dose. Other objectives include determining drug metabolism and bioavailability (how much drug reaches the circulation system). Phase I studies generally are short-term studies that involve monitoring toxicities in small cohorts of participants treated at consistently higher dose levels of the new drug in order to estimate the maximum tolerated dose.

Phase II trials build on the Phase I results in terms of which dose level or levels warrant further investigation. Phase II trials are usually fairly small-scale trials. In cancer studies, Phase II trials traditionally involve a single dose with a surrogate end point for mortality, such as change in tumor volume. The primary comparison of interest is the effect of the new regimen versus established response rates. In other diseases, such as cardiology, Phase II trials may involve multiple dose levels and randomization. The primary goals of a Phase II trial are to determine the optimal method of administration and examine the potential efficacy of a new regimen. Phase II trials generally have longer follow-up times than do Phase I trials. Within Phase II trials, participants are closely monitored for safety. In addition, pharmacokinetic, pharmacodynamic, or pharmacogenomic studies or a combination are often incorporated as part of the Phase II trial design. In many settings, two or more Phase II trials are undertaken prior to a Phase III trial.

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