The Pending Crisis
by Stephen L. DeFelice, M.D.
Our present system of drug discovery is almost designed not to cure the great diseases that confront us. There is no doubt that many will he cured in the distant future, hut it is unfortunate that many must wait.
That’s the view of author Stephen L. DeFelice, MD, a physician with varied experience in clinical drug research. As an academician, government researcher, and drug industry executive, he understands only too well how drug research is done and when it is leading us.
“Like most things in life, there is room for improvement in all responsible sectors,” says DeFelice.
On the Pharmaceutical industry: It still needs management that understands the nature of clinical drug development.”
On the academic community: It is still segmented and not fully aware of the principles of drug discovery.”
On the FDA: “It struggles with problems it cannot handle because society demands solutions. Yet the technology to solve the problems is simply not there.
“The greatest problem is history and its impact upon the Congress. The impact of thalidomide coupled with the swift rise in consumerism has led to congressional behavior that is concerned almost exclusively with safety. What Congress has forgotten, however, is that the discovery of the great new drugs has stopped. It seems that a constant flow of obstacles has created a socially dangerous and administratively ponderous milieu that hinders drug evaluation in man. Yet history clearly teaches that drugs are discovered in man. More exploratory clinical research, therefore, must be done.
“Fortunately, these problems are solvable ones.”
In this book, he proposes that a new medical specialist is needed-the clinical drug developer or CDD, a generalist who can direct a drug through the societal roadblocks of drug discovery-. He also believes that congressional action is mandatory in order to remove some of the significant obstacles.
“Let’s be honest,” he says. “Though the great drugs have stopped, nobody is talking about it.
“Perhaps this book will at least start a conversation.”
“There is substantial evidence of a decline in discovery and development of new types of medicinal drugs. Perhaps even more disturbing than the actual decline, however, is the complacency with which it is being met.”
“But consumerism also requires-though in far more subtle fashion-consumer protection by stimulating development of new and better drugs that lessen or eliminate disease morbidity and mortality.”
“One may rightfully wonder what human diseases are still uncontrolled because the drug that would have safely cured them was too toxic, or ineffective, in dogs or rats.”
“Perhaps the basic responsibility of the clinical drug developer for some years to come will be to develop a more imaginative, sophisticated, efficient, and safe methodology for testing drugs in man at a far earlier stage in their development.”
“Since man is the primary point of interest in the development of new drugs, it is man who should be studied. The medicinal chemists can produce new compounds and the biologist can evaluate the initial activity of these compounds, but we cannot discover the potential of many new compounds until they are studied in man.”
“As the drug research process continues to become more complex, and the demands of consumerism more dichotomous, clinical drug development must of necessity become the critical specialty that can deal with the science of drug discovery and development and the politics that surround that process.”
Dr. DeFelice brings to Drug Discovery a broad experience in academic, governmental, and pharmaceutical chemical research. He received his MD degree from Jefferson Medical College and served as a Fellow in Clinical Pharmacology at St. Vincent’s Hospital and Medical Center, New York. He was appointed Chief, Section of Clinical Pharmacology, Division of Medicinal Chemistry, Walter Reed Army Institute of Research, and also held the position of Medical Director of Pfizer Laboratories. Dr. DeFelice is now Executive Vice President and Medical Director of Clinical Resources, Inc., a consultant organization for pharmaceutical products.
To Begin With
A Definition of Terms
Factors Involved in Drug Activity
The Comparative Data Game
From Animal to Man
The First of the Phases
Phases II, III, and So-called IV
The impact of the thalidomide episode on American drug development has been substantial. Not only was it responsible for the passage of the 1962 Kefauver-Harris amendments, but it lead to an everincreasing stress on the safety of the FDA drug approval process. As a result, the loss to the public from delays in approval of important new drugs has been de-emphasized, so that the U.S. now lags behind many other countries in regard to the availability of new chemical entities. (We were the 41st country to approve lithium as a psychopharmacologic agent, and the 51st country to approve the important antitubercular drug rifampin.)
In this book, Dr. DeFelice deals with the key issues in clinical drug development-the process itself and the individuals who participate in that process. If the mechanisms are faulty, inefficient, or ponderous, the public will suffer. If the men and women who are the active participants in the process are deficient in ability or training or logic, again, the sick patient pays the price. This book’s important message-to me at least-is that we are stressing the nonclinical aspects of drug development too much and not stressing sufficiently the early and adequate study of drug candidates in man. These errors are in large part attributable to the noble goal, unfortunately not achieved by such emphasis, of preventing harm to the public. One cannot argue with safety measures that work; one can argue with those that do not, but merely provide, at great cost, the illusion of safeguards and wisdom.
Louis Lasagna, MD
Rochester, New York
November 9, 1971