Clinical drug development, four

Clinical drug development follows a sequential process. By convention, development of a new drug in humans is divided into four phases preapproval segments (Phases 1 through 3) and a postapproval segment (Phase The definitions of the three preapproval... 

Clinical drug development is generally divided into four phases Phase I through Phase 4. For each study conducted within a particular phase, specific information is collected according to the requirements for individual drugs being developed. Collection of safety, efficacy, and pharmacokinetic data is the focus of most clinical trials. Although these topics appear to be distinct disciplines. 

Serious rash Four patients treated with tiagabine during premarketing clinical testing developed what were considered to be serious rashes. In 2 patients, the rash was described as maculopapular in 1 it was described as vesiculobullous and in the fourth case, a diagnosis of Stevens-Johnson syndrome was made. Drug associated rash can, if extensive and serious, cause irreversible morbidity, even death. 

The components of preclinical drug development can be divided into four general areas that include (1) in vitro studies to define a new agent s pharmacologic properties (2) drug supply and manufacturing, (3) drug formulation, and, finally, (4) in vivo studies in animal models to provide an initial proof of therapeutic principle and demonstrate the potential for clinical efficacy. 

FIGURE 2.3 An overview of the drug development process that illustrates the activities within the four major stages of drug development drug discovery, preclinical development, clinical development, and manufacturing. (Courtesy of Milestone Development Services, Newtown, PA, 1998. With permission.)... 

Streptomycin (Boxes 20-B, 20-H) was introduced into clinical use against tuberculosis in about 1943. However, resistant mutants always survived until newer drugs were developed. Isonicotinylhydrazide (isoniazid) is especially effective in combinations with suitable antibiotics and other drugs. The four-drug combination isoniazid, rifampicin (Box 28-A), pyrazinamide, and ethambutol is often used. Nevertheless, bacteria resistant to all of these have developed. 

The safety of medicines is under evaluation throughout the drug development cycle. This process starts before humans are exposed, and continues during the clinical development and post-marketing phases. Broadly, the safety of a medicine is tested in four phases, each of which produces different types of data. These are as follows ... 

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