American Medical Association whose expanded program of information to physicians regarding drugs was explained to this committee by Dr. Hussey. It is my belief that the Food and Drug Administration and the American Medical Association could cooperate under the proposed law to the advantage of patients and the public.

The requirement of evidence regarding efficacy before a drug is marketed will mean that all drug manufacturers will obtain adequate information regarding efficacy, and this information will make the evaluation by the Council on Drugs of the American Medical Association more complete and thus more authoritative. On the other side of the picture, the council on drugs will be available to furnish expert opinion to the Food and Drug Administration.

With regard to the latter, some people have expressed misgivings that the Food and Drug Administration may be tempted to abuse the added powers given to them in the proposed bill by becoming dictatorial. I believe that there should be checks and balances on the power of Government agencies whenever this is possible. Accordingly, I would suggest that a provision be included in the bill that the Secretary of Health, Education, and Welfare be expected to call upon panels of experts and disinterested agencies and groups for their opinions before making important decisions regarding the efficacy and toxicity of drugs. I would also urge that appropriations for the Food and Drug Administration include provisions for the expenses incident. to the work of advisory panels and committees.

Senator KEFAUVER. Is that the end of that part of your statement? I see it is not. Proceed.

Dr. DOWLING. I do not believe that the provisions in the bill under which a copy of the information accompanying the package of a drug will be distributed to physicians will replace the program of information which is being started by the American Medical Association, because the package information is a bare skeleton outline containing the basic and most essential information.

It is not an expression of opinion, whereas the publications initiated. by the Council on Drugs of the American Medical Association will contain the considered opinions of experts as well as amplified information which could not possibly be included in package information because of its bulk.

Likewise, the provision that advertisements shall include a warning. of harmful effects and a correct statement of a drug's efficacy will be a signal to the doctor to learn more about the drug if he sees something in the advertisement with which he was not previously familiar, and a warning to abstain from prescribing the drug until he does obtain further information.

Senator KEFAUVER. The next part of your statement takes up another subject.

I think your suggestion that panels be included to help the Secretary of Health, Education, and Welfare is a very excellent one. We know that in many cases panels have been used, as in the case of Chloromycetin.

Dr. DOWLING. If I may say so, Senator, I was on that panel myself. Senator KEFAUVER. Yes.

We would certainly recommend very strongly and place it in the report or in the bill that in the matter of passing on efficacy, panels

such as the Chloromycetin panel be used to the fullest extent and that appropriations be enlarged to give the Food and Drug Administration the necessary funds which they have really never had, and also funds to pay the expenses of the panel of experts.

Also in that connection, I have stated before that I would think the Food and Drug Administration would want to use voluntary organizations and their efforts to the fullest extent in connection with generic names, which I believe you are going to discuss next.

Mr. CHUMBRIS. I would like to ask the doctor a question.
Senator KEFAUVER. The Commissioner or the doctor?

Mr. CHUMBRIS. The Commissioner, Mr. Larrick. Since the bill has been introduced, have you made any attempt to determine what additional appropriations you would need for the testing of efficacy across the board?

Mr. LARRICK. No; we have not priced that out yet.

Senator KEFAUVER. But you told me many times that you are operating on

Mr. LARRICK. A shoestring.

Senator KEFAUVER. A shoestring?

Mr. LARRICK. That is right.

Senator KEFAUVER. For what you are doing now you need more money?

Mr. LARRICK. That is right.

Senator KEFAUVER. I think you do.

Mr. CHUMBRIS. May I ask this question. You are operating on a shoestring now; is that right?

Mr. LARRICK. That is right.

Mr. CHUMBRIS. Of the drugs on which you make tests for efficacy, which you do under certain laws-is that correct?

Mr. LARRICK. Ordinarily, the tests for efficacy on antibiotics and insulin are made by the people in the universities. We do some efficacy testing and, also, if we have reason to doubt the honesty of the work that is submitted to us, we go out and get somebody to do work for us; but I certainly agree with Dr. Dowling that that sort of thing and expert panels need to be very much expanded if we are going to discharge our responsibilities.

Mr. CHUMBRIS. My next question is this: If you are given the responsibility for testing for efficacy of all drugs, how much of an additional load would that be on the Food and Drug Administration? In other words, what percentage of the new drugs that come in come within the category of testing for efficacy?

Mr. LARRICK. I do not think that the Food and Drug Administration should ever be required to test all new drugs. That would be virtually an impossible task.

I think we need testing done in these fine institutions outside and then have that recorded in the proper form and then presented to our people for appraising. Then, if our people do not feel competent to pass on them with finality-it involves very complicated matters then they should go outside and get the help of people who are the leaders in that particular field.

Mr. CHUMBRIS. Thank you.

Senator KEFAUVER. I want to add that that is in line with what I said, that it would be expected that you would use panels of experts

from hospitals, institutions, and elsewhere to do the main body of work, and then they would submit it to you.

Mr. LARRICK. Right.

Senator KEFAUVER. For final approval.

Mr. LARRICK. Right.

Senator KEFAUVER. Mr. Larrick, you have been testing certain antibiotics for efficacy under the required statutes?

Mr. LARRICK. That is right.

Senator KEFAUVER. That has worked out satisfactorily, has it not? Mr. LARRICK. I think reasonably well. I would prefer to have most of the efficacy and safety testing done by people outside. Senator KEFAUVER. By panels of experts?

Mr. LARRICK. Well, not necessarily panels. It could be done by universities. You could get them to do the work, then send it to the Food and Drug Administration, and then they take it to a panel and they appraise it.

Senator KEFAUVER. But you would have the final responsibility? Mr. LARRICK. That is right.

We would have the final responsibility with the manufacturer always having recourse to the courts, if he does not agree with our decision.

Senator KEFAUVER. Or the manufacturer submitting other information?

Mr. LARRICK. Right.

Senator KEFAUVER. If you are not satisfied?

Mr. LARRICK. Correct.

Senator KEFAUVER. Some companies are more thorough in what they submit than other companies?

Mr. LARRICK. That is certainly true.

Senator KEFAUVER. But the principal requirements of efficacy for diabetic drugs and antibiotics have worked for the benefit of the physician and the protection of the health of the public generally, in your opinion?

Mr. LARRICK. Yes. And I do not think that it has interfered with commerce in the drugs.

Senator KEFAUVER. It has not interfered with the legitimate aims of the pharmaceutical drug manufacturers?

Mr. LARRICK. No.

Senator KEFAUVER. You have had years of experience with efficacy? Mr. LARRICK. Experience for over 20 years.

Mr. CHUMBRIS. Commissioner, on that point again, of the new drugs that you pass on now, besides the safety factor, how much does efficacy come into play on these new drugs that you pass on, although it is not even in the law?

Mr. LARRICK. There is virtually no drug-and I am not a doctor of medicine that is entirely safe. Almost all drugs have potentialities for harm to some people, and our medical people always have to contrast the good against the bad.

Mr. CHUMBRIS. Perhaps I have not made my question clear. My question is this: Under the law now you have to check for safety? Mr. LARRICK. Right.

Mr. CHUMBRIS. You do not have to check for efficacy except in the specific laws that we have mentioned, insulin and antibiotics?

Mr. LARRICK. That is quite right, but

Mr. CHUMBRIS. Let me finish my question.

But in doing so, in your examinations and in your tests for safety, do you also take into consideration efficacy before you grant a new drug?

Mr. LARRICK. Yes.

Mr. CHUMBRIS. Even though you are not required to by law?
Mr. LARRICK. Yes.

Mr. CHUMBRIS. In how many cases would you say was that, as to percentage of new drugs that come on the market?

Mr. LARRICK. I would say we take that into account in all cases, but if we do not agree with the manufacturer on efficacy, the law does not give us clear authority to turn it down on that basis.

Mr. FENSTERWALD. Mr. Larrick, would you sum it up by saying you cannot separate safety from efficacy when you are testing prescription drugs?

Mr. LARRICK. Exactly.

Senator KEFAUVER. If the manufacturer does not agree with you on your voluntary finding about efficacy, under the present law you do not have clear authority to do anything about it?

Mr. LARRICK. No.

Senator KEFAUVER. And you think you should have that authority? Mr. LARRICK. We do.

Senator KEFAUVER. All right; let us proceed.

Dr. DOWLING. Several of the provisions in the act pertain to names. At present the decision on the nonproprietary name of a drug must be reached by agreement by the manufacturer, the American Medical Association and the U.S. Pharmacopoeia. It is sometimes impossible to get the producer to agree to a simple name or to a name that is similar to the names of other compounds in the same class. Consequently, some of the names in the "U.S. Pharmacopoeia" and "New and Nonofficial Drugs" (which is published by the American Medical Association) are tongue-twisters, and sometimes, too, drugs of similar chemical structure and with similar actions have entirely different names. The physician has learned classifications of anatomical structures and classifications of bacteria which are simplified as much as possible and which are based on similarly of names for similar structures or similar micro-organisms. He desperately needs such a classification of drugs. The proposed act would help the presently operating agencies (the AMA and the USP) to make such a list and would put the stamp of approval upon it when it was made. In the event that a producer was recalcitrant and would not agree to give a nonproprietary name to a drug which was simple and which fit in with the classification of similar drugs, the Secretary of Health, Education, and Welfare could step in and designate a suitable name. I believe that the knowledge on the part of manufacturers of drugs that such an action is possible will insure better cooperation with the Nomenclature Committee of the U.S. Pharmacopoeia and AMA than would otherwise occur.

I may add parenthetically, Senator, that I was on the Nomeclature Committee of the Council on Drugs of the AMA until recently, and I am quite familiar with what I am saying.

Senator KEFAUVER. Is this the end of your comments on the subject of nomenclature?

Dr. DOWLING. Yes.

Senator KEFAUVER. Then you had practical experience with the difficulty in getting the manufacturer to agree with the AMA Council on Drugs on a proper generic name?

Dr. DOWLING. I have.

Senator KEFAUVER. Can you give an example?

Dr. DOWLING. I am afraid I cannot because there were so many. I could give you an example of drugs, of names which are very difficult to pronounce.

Senator KEFAUVER. Tell us two or three.

Dr. DOWLING. Chlorodiazopoxide, for instance, is one that comes to my mind.

Mr. WALLACE. Would you suggest another change in that, Doctor? Dr. DOWLING. I could not suggest it right off without studying the chemical structure of the drug and the analoges of the drug.

Mr. WALLACE. Dr. Goodman testified that there are many, many problems connected with the names, that in many cases it could not be helped just because of the chemical structure of the drug, and that you needed to have the full name that you just named.

What was the name of that drug you just mentioned?

Dr. DOWLING. Chlorodiazopoxide.

Mr. WALLACE. Is there a way that you could suggest to shorten that up?

The question I am getting to is this, Doctor: Is it a lack of cooperation or is it just a problem necessitated by the chemicals that are in the drug?

Dr. DOWLING. I am glad you asked that question because under the present situation where the naming of drugs has been a question of jockeying back and forth and persuading, we have had to accept compromises.

On the other hand, if we had clear authority to proceed and to know that these names would be official names once they were decided upon, the entire system of nomenclature could be simplified.

I can use an example from Dr. Goodman's testimony. This is page 19 of his testimony where he states that:

The owners of the drug assign to it the name Declomycin, a four-syllable word, but the generic name is 12 syllables long; namely, Dimethylchlortetracyclinehydrochloride.

And he goes on to say that this occurred

because those responsible for this name labored under the necessary obligation to indicate that the drug is the hydrochloride and that it is the dimethylated congener of the parent compound chlortetracycline.

However, we could simplify chlortetracycline. We could simplify tetracycline which is the stem word for chlortetracycyline, oxytetracycline, and dimethylchlortetracycline. We could, for instance, say, tetcine which would mean tetracycline. We could change the stem word. Then we could say dimetetcine, which would be dimethylchlortetracycline. There are many other changes that we could make in the entire nomenclature, if there was reason to believe that everyone would go along with it.

Mr. WALLACE. The point I am making, Doctor, is that you have a real problem of nomenclature; is that not correct?

Dr. DOWLING. Absolutely.