Pharmacoepidemiology

Drug Development and Approval

Approval of a pharmaceutical product for marketing in the United States requires extensive testing and a determination by the Food and Drug Administration (FDA) that its benefits outweigh its risks for the intended use or indication. Before a medicine is tested in humans, it is studied and evaluated extensively in the laboratory and in animal models. The type and extent of testing depends on the nature of the chemical being studied and the indication for use that the sponsor is pursuing. Before clinical testing can begin, the product sponsor submits an investigational new drug application (IND) to the FDA. An IND summarizes the preclinical study results and contains a detailed plan for clinical testing.

Clinical testing is divided into three unique phases. Phase I is the first use of a medication in humans and, as such, is usually limited to a small group of healthy individuals. The primary purpose of this first phase is to determine the safety of the drug in humans. Within Phase I, scientists seek to determine a safe dosing range, how the drug is handled by the body (pharmacokinetics), and its action or effect at various dosages (pharmacodynamics). Phase II studies are generally small clinical trials in which a drug is tested in patients to further characterize its safety profile and determine which dosages and dosing schedules will be tested for approval. Phase III clinical trials are the randomized studies in the intended patient population. In Phase III trials, the new drug is compared with a placebo, or in cases where it is unethical to deny or delay treatment, an alternative treatment—typically the standard of care. The use of such ‘active-control’ trials relies on historical data for assurance that the alternative treatment is more effective than placebo, while testing for equivalence between the new and control drugs.

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