Assessment of new drugs (i.e., new molecular entities [NMEs]) is based on the New Drug Application (NDA) or the Biologic Licensing Application (BLA)—dossiers submitted by the drug sponsor that include all data from preclinical and clinical studies on safety and efficacy, proposed labeling, and manufacturing details. A team from CDER’s Office of New Drugs reviews the dossiers; communication with the sponsor occurs throughout the process to address scientific, medical, and procedural issues. The FDA uses advisory committees of external scientific experts for advice and opinions to broaden its basis for decision making on an NDA/BLA or regulatory issue.
For a drug to win approval, the FDA does not require that it be better than products already available, only that it be effective (better than nothing [i.e., placebo]) and fairly safe (Deyo, 2004). A drug is determined to be effective if it achieves a “surrogate outcome” (e.g., lowers cholesterol) without its effects on life expectancy being known. The FDA does not approve every use for which a drug may be prescribed by a clinician, only the use evaluated during its clinical trial.
Some of the risks associated with a new drug are not known at the time of regulatory review because the data from clinical trials are limited in terms of patient population, study size, and/or duration. Consequently, drugs must continue to be evaluated as they are used in clinical settings to detect less frequent but significant adverse side effects, long-term effects, or effects in different patient populations. Two mechanisms are available for this purpose: (1) postmarket surveillance studies, and (2) the FDA’s adverse event reporting systems (see later in the chapter). Both approaches rely on manufacturers to collect, evaluate, and report data on their own products (Fontanarosa et al., 2004).
Postmarket studies can be designed to observe a drug’s effects in a larger, more heterogeneous population over 3–4 years (Berndt et al., 2005). The FDA requires postmarket studies as a condition for approval in only two product categories—drugs granted fast track status and drugs for which the manufacturer desires a pediatric indication (Fontanarosa et al., 2004). Such studies are optional for other product categories, although strongly encouraged. Manufacturers complete fewer than half of the postmarket studies they commit to undertaking as a condition for approval (FR, 2004a; Fontanarosa et al., 2004). At the request of the FDA, the IOM Committee on Assessment of the U.S. Drug Safety System is evaluating the agency’s postmarketing surveillance. More detail on surveillance systems is given in