Clinical Pharmacology: Bridging Discovery and Practice (2007)

Eloquently placed in this journal, apparent in scientific meetings, and in the pathway of numerous initiatives worldwide lies clinical pharmacology—our scientific and medical bridge to therapeutics. It has been 66 years since publication of the first edition of the classic textbook The Pharmacological Basis of Therapeutics by Professors Louis Goodman and Alfred Gilman. Their objectives were to focus on “the correlation of pharmacology, with related medical sciences, the reinterpretation of the actions and uses of drugs from the viewpoint of important advances in medicine, and the placing of emphasis on the applications of pharmacodynamics to therapeutics.”1 Nineteen years later, in January 1960, the first issue of Clinical Pharmacology and Therapeutics was published. In the opening editorial, Walter Modell, MD, Director of Clinical Pharmacology at Cornell University Medical College and inaugural Editor, stated that the purpose of this journal was to “bring together publications of high quality on problems in the evaluation of the actions and effects of drugs in man”. Professor Modell continued, “Because of the tremendous number of new drugs now being regularly introduced into medicine, problems of their pharmacologic and therapeutic evaluation have become matters of great practical importance.”2 Today's challenges—or, better stated, opportunities—that face the discipline of clinical pharmacology are truly monumental. The Rion-Antirion bridge, shown on the cover of this issue, crosses the Corinth Strait and connects the Peloponnesian peninsula with central Greece. This connection had been conceived in antiquity but was not realized until 2004. For clinical pharmacology, fruition of the connection between discovery and practice, by comparison to this geographic linkage, has been precocious, albeit no more easily nor simply achieved. The health sciences have enjoyed an exponentially expanding base of knowledge that has afforded vast numbers of finite discoveries that have infinite opportunities for translation into better therapies for patients. The challenges of rigorously and systematically developing and applying these therapies to humans have been large but not insurmountable. The bridge is in place, and traffic is increasing. At the time of writing this editorial, PubMed returns 8,609 references when searching Clinical Pharmacology and Therapeutics. The numbers of drugs that Professor Modell described as being “tremendous” in 1960 now require the adverb-adjective combination of “immensely tremendous” to even modestly describe the current situation. In January 1960, the Food and Drug Administration approved 14 new drug/drug combinations and package changes.3 In January 2007 this total increased to 124 listings. Despite many of these items being labeling revisions, all clearly represent activities that resulted from one or more of the elements of the discovery/development/regulatory/utilization (DDRU) continuum,4 all of which are embraced and strategically integrated into the American Society of Clinical Pharmacology and Therapeutics. Furthermore, this nearly 10-fold increase in products and applications tallies only what has occurred in the United States and vastly underrepresents the increase in global drug development. The practice of therapeutics and all its supporting activities has grown exponentially. The objectives stated in the first edition of Goodman and Gilman's classic pharmacology textbook are as valid today as when written in the last century. This is despite some minor shift in the scope of pharmacology from what they originally described to include “pharmacy and compounding issues to clinical applications.”1 Our journal, Clinical Pharmacology and Therapeutics, relaunched in January 2007, is in natural evolution from what was described in its objectives of 1960. In fact, one of the more intriguing articles from volume 1 is a commentary entitled “Transposition of Drug Studies from Laboratory to Clinic.”5 This article clearly delineates the strengths and limitations of this translation in the science and society of 1960. Many of the issues raised would still be considered valid today. Thus, as with the engineering principles underlying the Rion-Antirion bridge, the scientific principles that underlie the discipline of clinical pharmacology are sound. What has changed in the past 47 years since the first issue of Clinical Pharmacology and Therapeutics is the benefit gained from more specifically addressing issues that are “transforming the practice of clinical pharmacology.”4 We are happy to present several articles in this month's issue that address the bridging theme. The articles include a discussion of nuclear transport as a new target for therapy, the development of a model for tumor growth that will aid drug development, a highlighting of the promise of personalized medicine, an examination of the regulatory issues related to prescribing opioids, and a description of the educational training program for clinical pharmacology at the National Institutes of Health in the United States. The challenges for clinical pharmacology as a discipline are numerous. One aspect that will be particularly important is better integration of the discipline into the fabric of basic and clinical training in the health sciences. The potential for a rapidly expanding role for clinical pharmacology in continued rationale drug discovery, development, and application requires adequate numbers of trained contributors. Hence all trained in the health professions or the sciences that underlie medicine should understand the discipline. Ongoing discussions and debates have characterized the ideal structure of clinical pharmacology for inclusion in colleges of medicine and pharmacy. One might further argue that the integration of clinical pharmacology into curricula should occur even at the immediately postsecondary undergraduate level. If we as a profession expect the lay public and our lawmakers to understand our and their needs with respect to clinical pharmacology, then we should sensitively integrate clinical pharmacology more broadly into the undergraduate curriculum in our colleges and universities. The general public is already exposed to clinical pharmacology—albeit at the level of direct consumer advertising or a perusal of over-the-counter pharmacy shelves. It would thus seem that providing the next generation of consumers with an understanding of clinical pharmacology not only would prove valuable to them as a way to understand their eventual diseases and treatments but would sensitize them to the need for this discipline. Scientific advances and their potential to influence therapeutics have truly increased the need for clinical pharmacology which is a natural cross-disciplinary juncture and bridge for science and medicine. As with the exponential growth of therapeutics regulated by the Food and Drug Administration in the United States, the advances of the past 50 to 60 years may easily be eclipsed by those that will occur in the next 5 to 6 years. These are indeed exciting times for clinical pharmacology.