first place to take in hand and cure some such as all others have given up for lost and dead. Physicians get neither name nor fame by pricking of wheals, or picking out thistles, or by laying of plaisters to the scratch

of a pint every old woman can do this. But if they would have a name and fame

if they will have it quickly, they must, as I said, do some great and desperate cures. Let them fetch one to life that was dead; let them recover one to his wits that was mad; let them make one that was born blind to see; or let them give rip wits to a fool; these are notable cures; and he that can do thus; and if he doth thus first, he shall have the name and fame he desires; he may lie abed till noon."

Statement on S. 1552

by

Louis Lasagna, M. D.

To be presented July 19, 1961

I am here in response to an invitation from the subcommittee to express my opinions concerning Senate Bill 1552. This statement represents a synthesis of views, since in preparing it I have consulted fully with colleagues in medical schools as well as with those in the drug industry. Nevertheless, I wish to stress the fact that the statement's final form is one for which I take personal responsibility and which is in no way to be interpreted as the opinion of any of my colleagues, or of the Johns Hopkins University, School of Medicine, or Hospital. The statement is based on my experience over the last 17 years as a medical student, physician, and teacher, and especially on my activities during the last 9 years as a research worker in, and teacher of, clinical pharmacology.

I should like to emphasize the reasons for my testimony. I am not here to help achieve any purely destructive ends. I have no desire to destroy the medical profession, the patent system, free enterprise, incentive, research, or the American drug industry. My daily activities are closely related to drugs and the pharmaceutical industry, and I have enjoyed pleasant and scientifically useful relationships with many drug houses. Serving as I do in the role of a liaison man between industry and the academic world, it would be the most reckless of approaches for me to try to eliminate the source of most of the compounds our research group studies each year. Nor am I inclined to favor unnecessary restrictive

regulations by any administrative bodies--be they academic, professional,

or governmental.

What I am for, is an improvement in those aspects of drug development which currently work to the detriment of the patients and physicians of this country. I know of no responsible physician, in or out of the drug industry, who believes that clinical pharmacology is being optimally handled at present, and I believe the important question to ask is: "What measures can be taken in regard to new drug development which will improve patient care and physician education?" It is my opinion that some of the proposed changes in the law embodied in S. 1552 are steps in the direction of such improvement. Unfortunately, I must plead ignorance concerning the patent laws and

the Sherman Anti-Trust Act. I have only a layman's knowledge on such matters, and see no reason to waste the committee's time with my opinion on these aspects of the bill. The only comment I have on these sections is that I would generally favor patent law changes which strengthen the hand of individual scientists or firms responsible for important new therapeutic agents. I say this because of the unsatisfactory atmosphere now surrounding new drug developments. At present, when a drug of unquestioned merit is put on the market, the company whose imagination and know-how has been responsible for the break-through is faced with the possibility that within a short period of time a half-dozen or more "pharmacologic shadows" will be introduced by competing firms, almost all of them representing minor advances or no advance at all, but one or more of which may purloin a good piece of the market away from the first drug. The result is a fantastic pressure on drug houses to assemble data in a hurry and to market at the earliest possible date. Were this pressure merely to speed up the process of drug development,

no one would have any serious objection. But the stage is also set for hasty and premature decisions based on inconclusive data of dubious merit. This unfavorable atmosphere is not, I might add, a mirage of my own imagination. It has been criticized by many responsible figures in the field of medicine, including such well-known medical editors as Dr. Joseph Garland and Dr. Walter Modell, who decry the "unnecessary expansion in the number of new products marketed each year" and the inability of the medical profession to "deal with the plethora of new drugs expertly, safely, effectively."

Regardless of whether the patent laws can, or should be, changed to prevent patent awards to drugs which do not represent "significant" improvements over older, chemically similar drugs, I believe it would be a tremendous advantage to the medical profession and to the public to have the comparative efficacy of "molecular manipulations" clearly spelled out by law. Nor do I see how the drug industry could object to such a request. It is unheard of for a pharmaceutical firm to place such a derivative on the market with the claim that it is "just as good as the other drugs already on the market". Every new phenothiazine tranquilizer, every new thiazide diuretic is promoted as superior to other competing drugs in some way. No respectable drug house making such claims should fear the request that they provide evidence for such superiority or stop making the claims.

This brings me to a crucial point in the reasoning. Can one realistically define and measure a "significant" improvement in therapeutic effect? I believe that the answer is "yes", if the definition is made sufficiently flerible and if the decisions are made by reasonable and capable scientists. Certainly a drug which provides a therapeutic effect previously unobtainable with available drugs is a significant therapeutic advance. Such an effect

was the antitubercular effect of streptomycin, an attribute not shared by such antibacterial agents as sulfonamides and penicillin.

Similarly, a drug which produces the same therapeutic effect as an older drug, but in a significantly higher percentage of patients, or at a lower cost in terms of toxicity, is a significant advance. An example here might be sulfadiazine's greater safety when contrasted with sulfanilamide or sulfapyridine, or secobarbital's greater hypnotic efficacy when contrasted with phenobarbital. A powerful analgesic as good as morphine but non-addicting to boot would be an unequivocal advance. The variants on this theme are numerous, but the principles are not of extraordinary complexity.

In the above, it has been implicit that one could not only define advantages, but also measure them. For the examples cited, clear-cut evidence would be easy to find. Is this always the case? In areas as widely diverse as hay-fever and cancer, pain and hypertension, scientifically acceptable experiments have been performed to distinguish good drugs from poor ones. In some areas of disease, it is easier to devise adequate tests than in others. Yet it remains a basic principle that in the absence of measurable evidence that two drugs differ, one must assume that the two drugs are alike. It is possible, of course, that two drugs might each cure 50% of patients, but each affect a different 50%. Thus the judicicus use of both drugs might allow the physician to treat 100% of patients successfully. Both such drugs should, of course, be on the market, but one would like evidence that the above facts are correct, rather than merely that either drug will relieve the same 50% of the population. It is often claimed that each new derivative should be allowed on the market because some patient might require the 999th modification instead of one of the preceding 998. Such reasoning quickly