From clinical research to clinical pharmacology

Modern clinical researchers, and in particular those involved in clinical trials, are completely knowledgeable with the concepts of comparators, double blind, randomization, placebos, statistical analysis and many others that have become almost common words in everyday language. However, probably not all of them have had the opportunity to assist, through the relevant references, to the birth of many of these terms or, at least, to the precise and definite use of them by the clinical investigators who, among other feats, shaped the field of clinical pharmacology.

In the Pharmacotherapy Revisited number 7 we pretend to revisit those papers that, in one way or another, have attracted our attention as landmarks in the development of clinical pharmacology. The results achieved in some of them are probably of little interest today, but what we want to honor is the methodological advances they provided at the time they were published. Thus, we still marvel at the quality of the research achieved by Harry Gold with the simple use of the stethoscope to record the heart rate, and celebrate the quality of the MRC trials and insights of Austin Bradford Hill. We also marvel at the work of Beecher’s group, measuring subjective responses, which was to be the cradle of the impressive figure of Louis Lasagna.

The role of the Geigy pharmaceutical company in fostering drug kinetics is very seldom acknowledged, but those who may believe that many of the nuts and bolts of the issue are of quite recent design should perhaps consider the 1953 paper of Burns et al. (among them the outstanding figure of BB Brodie) on phenylbutazone. On the other hand, the need to pay attention to the problem of transposition of drug studies from laboratory to clinic was also explicit in 1960.

The development of clinical pharmacology, a term coined by Gold in 1952, needed refinements and also attention to practical issues. Many contributed, but we still read with pleasure the inputs of Laurence, Wolf and Carr, which highlight once more the pivotal role of British and American authors in the early years of this discipline.

Finally, we would like to comment on the inclusion of two papers, one (of 1959!) showing that the effect of drugs on athletic performance can be rigorously measured and that not all people benefit even from those proven to work. The other, a Book Review published in 1969, provides what is for us the ultimate proof of the need of the double-blind technique. Interestingly enough, the hero of the story is a horse!

Let us end with a note on the pleasure that we derived from reading these articles when we were initially exposed to them and now in preparing this subjective selection. We sincerely hope that you may share this pleasure.

F. Bosch & S. Erill
Esteve Foundation
Barcelona, Spain