way that the Food and Drug Administration can decide whether you, now sick with a disease, will or will not receive a certain drug. Your physician makes that decision. You, trusting him, rely on his decision, just as I rely on my physician when he prescribes for me.

Mr. GRAY. I am merely raising the question of whether there is not a prior decision which FDA and only FDA can make under our present legal system. Must FDA not first decide whether the benefits to risk evaluation on a particular drug will be left to the individual doctor or will be made by the agency in not making that drug available!

Dr. HUSSEY. By law, the Food and Drug Administration admits the drug to the market. It is only then that the physician has the privilege of prescribing it.

Mr. GRAY. Now, the other part of my question concerns the statement you made that a Government agency should not have the preemptive right of a doctor in respect to passing on the effectiveness of a drug. You had stated somewhat earlier that AMA had always supported legislation to insure the safety of drugs.

Now both you and Commissioner Larrick, as I interpret it, have indicated that there is an intimate relationship between safety and efficacy, and that they cannot be artificially separated. I am wondering therefore if there is not some inconsistency here between your position on efficacy and your position on safety, particularly in the light of the positions which you say the association has taken on past drug legislation.

Dr. HUSSEY. We are turning back the clock in a sense.

The philosophic difference on this matter of efficacy related to a worry that the Food and Drug Administration would extend its consideration of the matter of efficacy to a consideration of matters of relative efficacy. At the same time amendments to the food and drug law were being considered-and they were considered over a long period of time and amended repeatedly before the act finally was passed-the Food and Drug Administration as well as the American Medical Association were thoroughly aware that the Food and Drug Administration weighed safety and efficacy before releasing a drug to the market on the basis of its being safe or unsafe. They looked at efficacy under the provisions of the 1938 act. This was a fact of life with the Food and Drug Administration.

It was contended that their privilege should not be extended further into a consideration of efficacy for the sake of efficacy alone, with the thought in mind that it might be possible under those circumstances for the Food and Drug Administration to decide that a drug proposed for marketing should not reach the market because it is no more effective or perhaps, to their mind, somewhat less effective than a similar drug already on the market. It cannot be judged until the drug reaches the market what its total effectiveness will be. There are sometimes dividends discovered after a drug reaches the market. For example, chlorothiazide, known to be a relatively safe and potent diuretic, was marketed as a diuretic. But in widespread use it was also discovered to have a very beneficial effect for the lowering of high blood pressure in patients having that disorder.

This kind of dividend, then, may be discovered only when the total effectivness of the drug is evaluated through widespread use.

Furthermore, a drug that is quite effective for one patient may not be generally as effective as another drug. If you judged it relatively, therefore, you might keep it off the market. If you judge it on the needs of the individual patient, you allow it on the market.

This is the point-this matter of relative efficacy.

Mr. FOUNTAIN. Mrs. Dwyer.

Mrs. DWYER. Dr. Hussey, will you pinpoint for us briefly those provisions of the drug amendments of 1962 to which the American Medical Association voiced objection!

Dr. HUSSEY. May I ask Mr. Donelan to answer that, Mrs. Dwyer! Mrs. DWYER. Yes.

Mr. DONELAN. Mrs. Dwyer, as Dr. Hussey indicated, S. 1552, which finally became the Drug Amendments of 1962, underwent a series of amendments. In the original version of the bill, there was a provision relating to patents on drugs which required that a drug have a significantly greater effect, as it were, than a similar drug with an existing patent. Now, this provision was related to other provisions in the original bill. It was opposed not only by the American Medical Association and the pharmaceutical manufacturers, but I do believe by the Administration itself. Our point on relative efficacy was raised on the original bill.

The bill was changed by the Senate committee twice, was changed on the floor, came over to the House and was considered with another bill. We were not sure what form the final bill was going to take; on the basis of past experience, we maintained our previous position and warned the House against this possibility. Whether or not relative efficacy will be determined under existing law, only the future can tell. It might be done under regulation if the administering agency became a trifle enthusiastic.

As you are aware, sometimes regulations exceed what Congress intends. We were concerned in this respect with the proposed regulations on investigational use of drugs. We felt in a few instances the agency was going beyond the scope of its authority.

It was on this basis that we were concerned with relative efficacy. Mrs. DWYER. Thank you.

Dr. GOLDBERG. May I ask a followup question on that? Are you implying there are provisions in the current law, resulting from the Drug Amendments of 1962, which the AMA opposes!

Mr. DONELAN. We have not had an opportunity to discuss the legislation except as it applied to regulations. There are no amendments pending before the Congress on which a position has been taken.

I feel sure, however, that our position in opposition to the efficacy provision still prevails because it has not been changed to my knowledge.

Dr. GOLDBERG. That has been reported in the press. Consequently, I was interested in knowing whether that is the official position of the American Medical Association.

Mr. DONELAN. It is. We would still oppose the efficacy provision on the same basis that we opposed it before.

Dr. GOLDBERG. Other than the efficacy provision, are there any other specific portions of the regulations issued by the Food and Drug Administration in support of the Drug Amendments of 1962 that the AMA is opposed to at the present time!

Mr. DONELAN. We have commented rather extensively on these regulations. To be frank with you, the comments were voluminous. I cannot recall all the details. I will be happy to check this point and inform the committee on behalf of the association.

Dr. GOLDBERG. Will you inform us of the current association position? I appreciate that there has been a period of give and take. Mr. DONELAN. Right.

Dr. GOLDBERG. Provisions that you may have objected to several months ago, may now be acceptable.

Mr. DONELAN. That is correct.

Dr. GOLDBERG. It will be helpful if you would cast this information in terms of the present thinking of the AMA with respect to the regulations as they now exist.

Mr. DONELAN. We will be happy to do so. (The information referred to follows:)

Hon. L. H. FOUNTAIN,

AMERICAN MEDICAL ASSOCIATION,
Chicago, Ill., July 13, 1964.

Subcommittee on Intergovernmental Relations, Committee on Government Operations, House of Representatives, Washington, D.C.

DEAR CONGRESSMAN FOUNTAIN: At the hearing on safety of drugs held by your subcommittee on March 25, 1964, Dr. Hugh H. Hussey testified on behalf of the American Medical Association. At that time he was questioned concerning the position of the AMA with respect to the regulations of the Food and Drug Administration relating to the 1962 amendments concerning the safety of drugs. The comments herein are in response to the query of Dr. Goldberg for this information.

These comments will be limited to (a) regulations pertaining to new drugs for investigational use; (b) regulations pertaining to prescription drug advertisements; and (c) the proposal of the FDA to delete from the list of oral drugs acceptable for certification antibiotics in combination with analgesic substances, antihistaminics, and caffeine.

Concerning the regulations pertaining to new drugs for investigational use this association continues its objection to the regulations insofar as they are an unnecessary burden upon the rescach and clinical investigation of drugs and act to deter, rather than advance, the cause of increasing medical knowledge concerning new drugs. By its nature, drug research cannot be stereotyped; the investigation of a drug must be flexible in order to determine the safety and toxicity of a drug as well as its therapeutic effects.

Furthermore, the present lack of qualified, competent drug researchers and clinical investigators would not be lessened by regulations requiring extensive and burdensome recording and reporting; such regulations would discourage the efforts of competent and qualified persons. Regulations should not so burden the drug investigator that research and investigation are no longer practical or feasible. The consequences of such a result could be disastrous in deterring expansion of medical knowledge achieved through clinical investigation of drugs.

As to the regulations pertaining to prescription drug advertisements, following the order of the Commissioner of Food and Drugs setting forth the prescription drug advertisement regulations, the AMA submitted formal objections and requested that a public hearing on its objectious be held. At a prehearing conference, it was agreed among the objectors that a public hearing would not be held, which decision was based upon a compromise agreement reached among the objectors and the FDA. However, the AMA's objections to the regulations were filed with the FDA and contained these reservations:

"The American Medical Association would like to make it clear, however, for the purposes of the record, that it does not agree with or consent to the basic premise of these regulations. That is, we do not agree that a prescription drug advertisement is by its nature or purpose an educational device for the medical profession. We continue to maintain that a prescription drug adver tisement is a reminder or informational piece, and that it is not the intended or proper vehicle for educating physicians as to the effectiveness, side effects, and contraindications of prescription drugs.

"In like manner, we do not concede or assent to the interpretation that the Secretary and the FDA have statutory authority to assume regulatory jurisdiction over the entire prescription drug advertisement, as contrasted to the 'brief summary' specifically mentioned in section 502 (n) of the act. We do not agree or concede that the Secretary and the FDA have statutory authority to require that the information on effectiveness, side effects, and contraindications must be in fair balance,' 'in reasonably close association,' and must have 'the same relative degree of prominence' throughout the entire advertisement. "Finally, we do not concede that there is statutory authority to require that an advertisement must set forth the side effects and contraindications for any other use or uses for which the dosage form advertised is commonly prescribed." In addition, pertaining to prescription drug advertisements, the AMA also objects to the regulations requiring the use of the generic name of a drug each time the proprietary name is used.

With respect to the proposal to delete from the list of oral drugs acceptable for certification antibiotics in combination with analgesic substances, antihistaminica, and caffeine, it must be noted that this proposal has not become effective. The AMA submitted its comments in opposition to the proposal on October 80, 1963.

By this action, the FDA seeks the removal of antibiotics from mixtures containing "cold remedies." It is the position of the AMA that such action would be without sanction of any law. As was indicated in our statement to the FDA, the presence of antimicrobials may be of value during the course of a common cold in patients having chronic pulmonary disease. Thus the antibiotic would be effective for an intended purpose; namely, the prevention of bacterial complications in some patients. We suggested that significant reduction of any misuse could be achieved by labeling such mixtures to reflect the limited value of the antibiotic. The physicians' privilege to prescribe should not be denied them unless it can be shown that one or more of the drugs in the mixture is unsafe or ineffective for the purpose intended. We believe that the elimination of these mixtures by regulatory fiat is an extreme action not authorized by existing law, and that a proper solution should be accompanied by voluntary educational programs and regulation of labeling misinformation.

We would appreciate it if his letter would be inserted in the printed record at the appropriate place in the testimony of our witness.

Sincerely,

Mr. FOUNTAIN. Mr. Gray.

F. J. L. BLASINGAME, M.D.,
Executive Vice President.

Mr. GRAY. With respect to one of the points made by Dr. Goldberg, I believe it was reported in the trade press fairly recently that one of the organs of AMA-I don't recall which one-had passed a resolution favoring the repeal of the efficacy provision of the 1962 drug amendments. Could you confirm that or not?

Dr. HUSSEY. I will confirm that. This was an action by the House of Delegates of the American Medical Association at its meeting in Portland in early December of last year.

Mr. GRAY. Would this, then, be considered the position of the AMA, itself!

Dr. HUSSEY. It would be.

Mr. FOUNTAIN. Doctor, I would like to ask several questions relating to matters which I think the average individual can understand and about which patients and consumers are concerned. To begin with, where does the doctor get his first information about a prescription drug!

Dr. HUSSEY. We hope that he gets his first information about a prescription drug-the first truly useful information-through his professional contacts, through his reading, consultation with other physicians, or attending meetings. In some instances, there is no question that the first information about a new drug reaches the physician through the agent of the pharmaceutical manufacturer.

Mr. FOUNTAIN. You referred to meetings. What kind of meetings take place to enable a very busy physician, who is somewhat like Members of Congress in this respect, to obtain such information!

Dr. HUSSEY. Meetings of his hospital staff which are held monthly in most instances. In some hospitals, division meetings are held at least weekly. Meetings of his professional societies: the county society, which usually meets monthly; the State medical society, which meets once or twice a year; and the annual conventions of the American Medical Association, which are held twice a year. The numerous other postgraduate programs that are going on constantly; locally and nationally.

For example, I learned only earlier this month that in California alone there were more than 1,400 identifiable, formal, postgraduate programs for physicians during 1963. These were programs from which the physicians could choose. I watched the attendance at one of these programs at the University of California. There was an amazing turnout.

Physicians are eager for knowledge and they find it.

Mr. FOUNTAIN. I am sure that is true. The problem we all have is in finding the time to get informed.

Is there anyone at most of your hospitals who makes a thorough study of drugs and gives the physician a briefing on those drugs, in case they do not find the time to read the abundance of material that comes out on them?

Dr. HUSSEY. It is possible that at some hospitals that kind of function is performed by the Committee on Pharmacy and Therapeutics, which is a part of the hospital organization. But more often it would be done either departmentally or on a staff-wide basis as part of staff meetings.

Mr. FOUNTAIN. Would you have a lot of general practitioners, not on the staff of a hospital, who would therefore not be able to take advantage of all these hospital briefings!

Dr. HUSSEY. If there were no general practitioners on the staff, they would not be attending a formal staff meeting.

In a locality like the District of Columbia, I can cite from my own experience that, for example, grand rounds of the Department of Medicine at the Georgetown University Medical School and Hospital were held weekly and were attended by a number of general practitioners. In that instance, they were members of the staff.

That kind of meeting is open to all physicians who want to attend and there were others attending from time to time depending on the topic to be discussed. Whether it was of interest to them or not, they would be there.

Mr. FOUNTAIN. Thank you very much, Doctor; we appreciate your coming.

Dr. HUSSEY. Thank you, sir.

Mr. FOUNTAIN. Our next witness is Dr. William S. Apple, executive director of the American Pharmaceutical Association.

I understand that Dr. Apple is accompanied by Dr. Edward G. Feldmann, who is director of the Scientific Division of the American Pharmaceutical Association.

We are delighted to have both of you gentlemen with us.

Before proceeding with your statement, Doctor, will you please tell us briefly of your professional background?