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The investigational new drug application—who benefits?

Nature Clinical Practice Oncology volume 3, pages 62–63 (2006)Cite this article

The FDA performs an important regulatory function in protecting the US public from the marketing of drugs that are either dangerous or not effective.1 The federal law that created the Investigational New Drug (IND) process—the Federal Food, Drug and Cosmetic Act—was enacted in 1938; it required that the FDA be informed before any new treatment was administered to humans.2 Unfortunately, in 1962, following the recognition of the teratogenic effect of thalidomide in children born to women who were receiving this drug outside the US, Congress enacted a new amendment to the original Food and Drug Act of 1938—the Kefauver–Harris Drug Amendments. This changed the IND process from one of notification to one of approval. It was now required that FDA officials approve the initiation of a phase I trial, so that FDA approval was necessary before a drug could be given to a human being. Since that legislation was passed, the requirements for the IND application have progressively escalated, as has the cost of new drug development. It is now estimated that the time from conception of a new drug to its approval is in excess of 15 years, and that over two-thirds of this time is devoted to pre-IND testing.3 During this 10-year period of delay, over six million Americans will die from cancer. Of course, if the progressively escalating requirements for preclinical data for an IND provided further protection for patients, they would be justified. But, tragically, at the time of the legislation in 1962, there was no known preclinical test that could have predicted the thalidomide disaster, and, to a large extent, the preclinical data obtained during the IND process are of only limited usefulness when progressing to clinical trial.4 With modern techniques, it is possible to approach a phase I trial in an objective and quantitative manner, using pharmacological techniques and sophisticated in vitro techniques for predicting potential effectiveness and toxicities. Unfortunately, innovative developments in science are not rapidly appreciated by regulatory officials employed by the FDA.

Although it is certain that the FDA employees who review IND applications are highly competent and well trained, it is nonetheless true that each individual is in a position where, should they approve an application that subsequently causes harmful effects in humans, it would be much to the detriment of their career. By contrast, if such a treatment were highly effective, they would get no reward for having been astute enough to allow the early introduction of this drug into clinical trial. Consequently, all of the social and psychological forces acting on this person are compelling them either to deny approval or to delay approval and require additional data, which is the usual response to an IND application.

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  1. Director of the Special Medical Education Programs and Director of the Adult Leukemia Research Program at The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Emil J Freireich

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Correspondence to Emil J Freireich.

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Freireich, E. The investigational new drug application—who benefits?. Nat Rev Clin Oncol 3, 62–63 (2006). https://doi.org/10.1038/ncponc0429

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