Why So Few New Cardiovascular Drugs Translate to the Clinics.

Abstract

There are multiple reasons for the failure to successfully translate new drugs to the clinics. One reason, noted by others, is the lack of reproducibility of studies and the problems with accuracy and rigor. However, another reason for translational failure has not been emphasized by others, that is, the lack of state-of-the-art cardiovascular measurements, because of effects of anesthesia, lack of direct measurements of cardiovascular function, and problems of species differences. In part, this is because of the impact of molecular medicine on traditional physiology, which not only affects priority for publication in top-tier journals, but also funding priorities for National Institutes of Health (NIH) study sections, resulting in the closure of almost all cardiovascular physiology laboratories, leaving the cardiovascular physiology in many molecular publications to incidental data that are not peer-reviewed and in many cases are inaccurate. It is the plea of this Viewpoint to correct this deficiency in expertise in our scientific community, a project with no simple solutions. It is widely recognized that relatively few cardiovascular therapeutic modalities are emerging from the plethora of studies in genetically altered mouse models over the past quarter century, for example, the success rate for new drug development projects in Phase II trials fell from 28% to 18%.1 The most popular explanation for this decline has been the irreproducibility of data, in that only in 20% to 25% of projects repeated in industry were the data completely in line with what was in the literature, often because published data were incorrect.1 The current Viewpoint offers a novel reason for failure of translation, that is, the difficulties, limitations, and errors in studying cardiovascular physiology in the 21st century. The goal of this Viewpoint is not to dwell on papers with false or inaccurate data, but rather to offer other reasons …