ARTICLE: FDA Regulation of Prescription Drugs

AUTHORS: Audrey L. Gassman, Christine P. Nguyen and Hylton V. Joffe

JOURNAL: N Engl J Med. 2017 Feb 16;376(7):674-682. doi: 10.1056/NEJMra1602972.

In 2015, approximately 4 billion prescriptions were filled at retail pharmacies in the United States.1 The Center for Drug Evaluation and Research (CDER) within the Food and Drug Administration (FDA) ensures that prescription drugs have reliable quality and purity and that they provide benefits that outweigh the risks for the intended population.2 The FDA does not develop drugs or conduct clinical trials; drug companies are responsible for those activities, with important contributions from universities and academic medical centers.3 The FDA provides guidance to drug companies, evaluates the data generated from their programs, and then determines whether a drug can be approved. The criteria for approval are substantial evidence of effectiveness and benefits that outweigh the risks and remaining uncertainties.4 After approval, the FDA monitors drugs by means of various data sources, including clinical trials, epidemiologic studies, and postmarketing reports.5 The purpose of this article is to provide clinicians who prescribe FDA-approved drugs with an understanding of the key aspects of drug regulation. We focus on CDER activities and data and do not cover products regulated by other FDA centers.


Drug companies are required to establish the effectiveness and safety of new drugs before marketing them.6 For substantial evidence of effectiveness, regulations require reports from “adequate and well-controlled investigations.”7 The plural form of “investigation” is interpreted as meaning that evidence from at least two adequate and well-controlled trials is required to support effectiveness. Positive results from two trials, as compared with a single trial, provide greater assurance that the findings are not due to chance or bias. However, the FDA can accept evidence from a single trial — for example, if a second trial is not feasible (e.g., in the case of a rare disease) or would be unethical (e.g., when a convincing survival benefit is shown in one trial) or if there is supporting evidence from related uses (e.g., evidence from another trial that tested the drug in a different phase of the disease in question).8-10 One study11 reported that approximately one third of new-drug approvals between 2005 and 2012 were based on a single pivotal trial. We found that for the 2011–2015 period, about 50% of new-drug approvals were based on a single pivotal trial, and nearly two thirds of those approvals were for the treatment of rare diseases (Drugs@FDA database).12 The law does not require a new drug to be better than, or as good as, another approved drug, but the FDA takes into account available treatments when determining whether a drug’s benefits outweigh its risks.

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