request with respect to furnishing clinical information upon which this evaluation could be made, is that not true?

Dr. HUSSEY. I do not know that I can answer that question directly. I would agree that there were manufacturers who did not seek the seal of acceptance for their products.

Mr. FLURRY. So that in that case you had no opportunity to pass upon the efficacy or the safety of the drug?

Dr. HUSSEY. Under present circumstances there is every opportunity for AMA through its Council on Drugs and its other agencies to review efficacy not only immediately but periodically, and to issue statements intended to bring physicians up to date on this as well as upon the point of toxicity. If I keep harking back to this matter of education of the physicians, it is because I feel so strongly about it.

Mr. FLURRY. I think the committee would agree with you that education is important. But as we found in the electrical equipment price hearings, sometimes communications fail. So that we are still left with the proposition that if the manufacturer does not choose to accept the principles upon which the educational program is based, it becomes ineffective and it does not redound to any benefit of the public or the physician.

Dr. HUSSEY. The manufacturer would have no choice in the matter as I view it. If we are talking now about a drug that is on the market, the manufacturer has placed it there. If the test of time and wide usage indicute that this drug is nonefficacious, that information would be published to the profession regardless of the manufacturer's wish in the matter.

Senator KEFAUVER. The Journal of the American Medicine is what you reach the medical profession with, but there are other medical magazines with as much circulation as yours, are there not?

Dr. HUSSEY. Not comparable professional journals, Senator. I believe that the Journal of the American Medical Association is the outstanding one in terms of its circulation.

If I may request, you asked a while ago about an item that we could not find immediately in testimony previously given before your committee. Dr. Howard has found the sentence that he had in mind presenting.

Senator KEFAUVER. All right, Dr. Howard.

Dr. HOWARD. This quotation from Mr. Larrick applies more or less to the present colloquy, also. Page 12127 of part 22 of the hearings, Mr. Larrick testified, after describing generally certain broad concepts of safety as the present law is administered, he said:

Because of the application by FDA of these broad concepts in interpreting the meaning of safety in the processing of new drug applications, with few exceptions the new drugs cleared by FDA have been adequately demonstrated to be both safe and efficacious. In addition to enforcing the safety concept as broadly as possible to insure efficacy, FDA constantly seeks in allowing new drug applications to become effective to advise manufacturers of any excessive or unsupported therapeutic claims for new drugs; in this way in many cases label claims are held to those that are adequately supported by scientific evidence. However

and this is the important sentence

the new drug procedures are not adequate to insure the efficacy of drugs which are essentially innocuous.

Mr. Larrick then went on to conclude:

We would endorse a proposal that the new drug section of the Food, Drug, and Cosmetic Act require a showing of efficacy as well as a showing of safety.

I submit that he, therefore, concluded that because he said the only gap, as he saw it, was the failure or the lack of authority by FDA to consider efficacy for innocuous drugs.

The point I am making is that this is an insignificant problem because innocuous drugs in the main are not prescription drugs.

Senator KEFAUVER. If it is not innocuous, then that would mean that it is efficacious, would it not? If it is completely innocuous, that is one thing, but if it is not innocuous, that would mean it was efficacious?

Dr. HOWARD. Mr. Larrick makes the point that he wants to have authority in a new statute to determine efficacy for innocuous drugs, and only for innocuous drugs.

Senator KEFAUVER. Because he is doing it by the back-door method at the present time.

Dr. HOWARD. He is relating efficacy to safety, and as he relates efficacy to safety.

Senator KEFAUVER. Why not let him do it directly and systematically rather than having him go through the back door?

Dr. HOWARD. He is not going through the back door. He is relating efficacy to safety and we have not questioned this interpretation and administration of the present law.

Mr. FLURRY. The point I was making, Doctor, is that there is no force of law behind the actions of AMA regardless of how worthy they may be, and they, therefore, cannot be made universally effective. Mr. STETLER. May I comment on this point?

Mr. FLURRY. I would like to call your attention to a book entitled "Medicine Makers of Kalamazoo," published in 1961, by a Mr. Engel, which is an authorized biography of the Upjohn Co. He states that:

In 1905, the American Medical Association set up the Council on Pharmacy and Chemistry to act as an authority on drugs. In order to clear the medical field of hundreds of drugs and drug mixtures of little or no value and pave the way to a more scientific approach to the treatment of disease, the council adopted a series of rigorous rules regarding trademarked mixtures of standard drugs especially. The action hit many pharmaceutical companies, Upjohn among them. Upjohn felt that it could not change its trademark policy to conform with the council's new rules. Since only council-approved products could be advertised in AMA publications, the advertising pages of the Journal of the American Medical Association and other AMA journals were closed to the Kalamazoo firm. Upjohn finally sought and obtained council acceptance for Upjohn products in 1937.

So that during that period the AMA had no occasion to pass upon the products of Upjohn, to issue any seal of acceptance or to force Upjohn to comply with the program of the AMA?

Mr. STETLER. May I comment on that point?

Senator KEFAUVER. All right.

Mr. STETLER. I think the point you raised concerning the effect of action by the American Medical Association or its council or its inability to enforce its action is a very crucial point. It was mentioned earlier, and I think we should mention it again. We oppose, in this statement, giving Food and Drug Administration the author

ity to determine efficacy. We do not mean by opposing this statute that no one should concern themselves with efficacy.

We think that the American Medical Asociation and others have a proper right to educate, to give to doctors any information that his been collected with respect to the efficacy or usefulness of a drug. Two points become important, though. One question is when you make this decision as to efficacy or when you give out the information concerning efficacy, and I think we have made it in our statement, the point being that it would be difficult, if not impossible, for the Food and Drug Administration or anyone else, including us, to make a decision concerning the efficacy of a new drug, that decision being determinative as to whether or not that drug is marketed.

Now secondarily, even if we were to make a premature decision and to publish it to the medical profession, this does not have the effect of law. It does not keep the drug off the market. And if we make a mistake, and we can, it will not keep that drug from being marketed.

I think that is the point we are trying to make in our statement. It is when you make the decision and what happens depending on who makes the decision.

Mr. FLURRY. If I put on the market a useless gadget, I am doing the public an injury, and as has been brought out here in other quotations, useless drugs or drugs that have no therapeutic effect are often harmful to the patient.

What right should any manufacturer have to place on the market a drug until it has been determined that it either has or does not have any useful purpose? Does the law not now, as the Senator pointed out earlier, provide for experimental use of new drugs before they are put on the commercial market? It seems to me that they should not be put on the commercial market until their efficacy has been determined.

Mr. STETLER. I believe it is our opinion and our position that there are provisions in the law now which permits Food and Drug to relate claims to proven clinical effect as to efficacy. Under this misbranding provisions of the Food and Drug Act, they have been successful, I believe, in removing from the market some of the drugs that were previously discussed, as worthless or not as efficacious as they were claimed to be.

Mr. FLURRY. I personally do not recall any provisions of the law with respect to efficacy other than antibiotics, insulin, and biologicals. But if we assume that such provision were in the present law, to go after those drugs for misbranding after they have been placed on the market, they may be caught by the FDA and they may not be caught by the FDA, but it seems to me that it is like locking the stable after the mule has been stolen. It is certainly a more expensive process for the FDA to trace down all of these drugs after they become dispersed in the market than it would be to pass upon these matters before they are put into the marketing channels of commerce. I wonder if you could refer us to the provisions of the law to which you refer?

Mr. STETLER. I am speaking about the provisions of the law as they exist in the statute and the law as administered presently by the Food and Drug Administration. I believe I am correct in my interpretation

or impression that when a new drug application is filed, the Food and Drug Administration does look to the claims as to the usefulness or effectiveness of what this drug will do and compares it with the clinical data that is filed with the new drug application.

Senator KEFAUVER. The impressive thing to me about this is that Dr. Hussey or any thinking person would testify as he has that we do not want drugs on the market that are useless, that are not efficacious. And he says that he thinks the American Medical Association, with its new spirit of getting things done and its new resolution can do something about it and can be set up to go by 1963.

But the trouble with that is that you cannot make the drug companies submit the information. You cannot get anything more than what they are willing to give you, and even if you do get the information, it only applies to what appears in the medical journal of the AMA. Other medical journals may not carry it. It does not relate to direct mail advertisements by the drug companies to their doctors. It does not relate to what the detail men tell the doctors.

So it only relates to a fraction of the media that persuade the doctors as to whether they should use the drug or not, and there it is following this voluntary approach. There is no way you can make the detailment of the drug companies give the same information as you write in the Journal of the AMA. There is no way you can require that the drug companies in their direct advertisement give that information. There is no way you can require them in the many other medical journals, of which there are about 400, to give information if AMA takes a dim view of this.

So you are only hitting one little point of persuasion when you pass on it when you publish the report in the Journal of the AMA, is that not true?

Dr. HUSSEY, This again is a matter of communication and authoritativeness. It is our intention to make so authoritative the declarations that we provide to the profession that the profession will look to this source for their information, and will be discerning in what they learn from other sources so as to exclude the chaff. This is equivalent in some respects to the effect that can be obtained throughout the Nation regarding any item of popular interest.

At the time of the election of the President, even though people might not read the newspaper, might not read other news media, might not watch television, it is hard to believe that throuughout the Nation following election day everyone would not know that a new President has been elected and what his name is. This is a chain reaction in a sense.

It happens constantly in the profession. Physicians communicate among themselves, transferring valid information from one to another. Senator KEFAUVER. You did not answer my question. The point is that you have one journal. There are 400 others. There is, for example, Dr. Welch's journal on antibiotics that we heard of—in all some 400 journals. Carrying it in the J.A.M.A. does not mean that they carry it. Many of them are received free by the doctors, whereas they have to pay for your magazine or most people do. We have been told, also, that the direct mail advertising is very influential, and even more influential than the detail men.

The surveys that your organization has conducted have shown the great influence and the importance of these other media. So you just hope that you may be more persuasive in the future. But in the meantime that is not protecting anybody, is it?

Dr. HUSSEY. In the meantime this program is in effect partially. The portion of the program that would reach completion would be the distribution of the new handbook on drugs. We currently publish information about drugs. We currently in our scientific meetings let the profession at large know about developments in therapy. We currently published "New and Non-Official Drugs."

Senator KEFAUVER. I think we have gone along far enough tonight. One important thought about this is that it must be related to the testimony we have heard here that when a patent expires on an old drug, the price naturally goes down, as it does after other companies start making it. Then there is a great effort on the part of the pharmaceutical manufacturers to produce something that the advertisers can talk about how efficacious it is, when, as a matter of fact, it is just the same or about the same as the old drug. By the time that is found out they have put on a promotion campaign and have sold a lot of it at a high price.

Then we have the other situation where we can be thankful that perhaps the Food and Drug Administration, in order to try to protect the public interest, is doing some investigation efficacy at the present time, but that is all the more argument as to why we ought to give them the direct right to do so. I think it is important also that that they have to do it, not that they just might do it or perhaps in some cases do it.

And then there are the cases such as the completely innocuous water with a little color aded to it. I suppose it does not come under this discussion of new drugs, but I read in the paper where somebody some time back was distilling sea water and selling it down in Florida.

So I think any blocks we can put in the way are important, including those that you would have, but I think it is also important that we have a law so that we will know that somebody has approved the usefulness of a drug.

I respectfully submit, sir, that your rule 7 recognizes the importance of efficacy. Dr. Smith used to be secretary to the council and he has written and spoken a great deal about it. He has opposed to putting drugs on the market unless they were afficacious. The Council on Drugs of AMA seems to be for it. We have two or three statutes here where it has worked very well. There are no criticisms from the American Medical Association. We have the special committee under Dr. Miller that studied the needs of the FDA and they came up with this. That was in their recommendation, in Secretary Flemming's recommendation, Mr. Larrick's recommendation; and respectfully, sir, I think the AMA has substantially changed its position. Your position is now that you do not want some official body to pass on efficacy. I cannot quite reconcile that with the previous statements I have seen of the AMA in the past.

My personal feeling is that the great, great weight is on the other side of your new position.

We will stand in recess until 10 o'clock in the morning.

(Whereupon, at 5:55 p.m., the hearing recessed, to reconvene at 10 a.m., Thursday, July 6, 1961.)