part of FDA’s statutory purview. (Chapter 4 addresses this topic in greater detail.) Thus, premarket studies typically do not answer questions of great concern to health care providers, patients, and payers: Which drug in a class works work best for most patients? Which is the best first line of treatment? Which is most cost-effective?

By definition, premarket trials do not address the implications of expansive off-label use, that is, use for conditions in which the given compound was not studied (or not approved) in tests submitted to FDA (Beck and Azari, 1998). A recent study found that 21 percent of the 725 million prescriptions written in 2001 were for off-label uses (Boodman, 2006).

Pre-New Drug Application Submission Meeting

As trials are completed and analyzed, the sponsor meets with the review team to go over the impending NDA submission; it is in the sponsor’s and FDA’s interest to anticipate issues so that the NDA is complete when submitted. For example, a 2006 report indicated that when sponsors met with CDER staff before submitting an NDA, there was a greater likelihood that the drug was approved on the first cycle (FDA News, 2006b).

According to FDA documents, the discussions include development of strategies to manage known risks (CDER, 2005b). ODS/OSE staff sometimes participate in the meetings; it may be the first time that ODS/OSE staff become involved in the IND. (When OND is reviewing a supplemental NDA for new labeling or manufacturing, ODS/OSE may be active in reviewing available postmarket data on the approved indication.)


In the last couple of years, FDA has received 110–120 NDAs per year (FDA and CDER, 2005). The average size is 235 MB with 250 files, the equivalent of almost 400 volumes of 500 pages each, or about 200,000 pages (Henderson, 2006). Often, an NDA does not arrive all at once—FDA allows gradual submission for fast track5 studies (rolling review). Sponsors are also required to provide additional data that become available during the review process.

Data management is a critical task with a project of this size. Scientific reviewers need sophisticated knowledge of and access to programs for managing and analyzing the data. In addition, because sponsors have some


“Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases” (FDA, 2006c).

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