It has selected laboratory data for patients on this drug in tabular form, for example. It is in very small print. The answer is "No," but the physician does get one particular form, or package insert on biological products, and I think that this should be continued. It is important. These other package inserts, in all sorts of sizes, are printed on what is commonly called in the trade, "bible paper.' Mr. GORDON. What do you mean by "bible paper”? Dr. GODDARD. Well, it is very thin. Mr. GORDON. You need a magnifying glass to read the print? Dr. GODDARD. That is true. Mr. GORDON. Dr. Goddard, doesn't this present situation really make the doctors more dependent on drug advertising and promotional activity? Dr. GODDARD. Yes. Of course, that is not their only source of information. But, as I have pointed out on numerous occasions, the industry does spend a significant amount of its income to educate the physicians through advertising. Mr. GORDON. Are you using that word with quotation marks? Dr. GODDARD. Well, I say advertising in this field is a form of education, and I am serious when I make that point. And the AMA also now recognizes this point, apparently in response to a recent position the Internal Revenue Service took with respect to their income on general advertising. They pointed out this was different from routine advertising and that it did serve an educational purpose. And I must agree with that. Mr. GORDON. Who took that position? Mr. GORDON. How about the IRS? Dr. GODDARD. They haven't responded to this, to my knowledge. But advertising apparently does influence the physicians' choice of the drug. Therefore, I think it is educational. And we are anxious to have a comprehensive, more impartial source of drug information readily available to every physician, every pharmacist and every hospital kept up to date with accurate prescribing information. Senator NELSON. I don't understand the mechanics of the delivery of the package insert. The doctor himself in his office just writes a prescription. The drugs, with some rare exceptions, come into the pharmacy. Does each package of prescription drugs, no matter how small, have to have an insert? Dr. GODDARD. That is correct. Senator NELSON. So then the doctor does not come in contact with that package insert Dr. GODDARD. Except for biological products, which tend to go directly to his office. Senator NELSON. What do you mean by "biological"? Dr. GODDARD. Well, vaccines and things of this nature, you see. Dr. GODDARD. That is correct. Senator NELSON. I see. Dr. GODDARD. And intravenous therapy in wards in the hospital are accompanied by the package insert. But by and large these are re ceived by the pharmacist and thrown away after he has a file of them, you see. The physician can call the pharmacy and get information on a drug. And some of them do this. But by and large they do not see them. So the system does not accomplish what it set out to accomplish at all. Senator NELSON. And do I understand that it is your position that if an acceptable compendium were adopted and published, you would be willing to remove the requirement that an insert be used except for biologicals? Dr. GODDARD. That is correct. Senator NELSON. Is the insert required by law or is it the result of an administrative ruling? Dr. GODDARD. Those are the conditions for the approval of a new drug. Yes, sir; statutory. Senator NELSON. By statute or by a ruling of the FDA? Dr. GODDARD. Statute. Senator NELSON. So you would have to change the law respecting the insert Dr. GODDARD. Mr. Goodrich, do you want to comment on that? Mr. GOODRICH. We have authority to exempt a prescription drug from the requirement of that detailed label where it is not necessary for the protection of the public health. We could do so if we had an alternative compendium available to the physician. Then it would not be necessary to carry that information in the packages. Senator NELSON. Go ahead, Doctor. I have some more questions, but I think you cover some of them in the statement. Dr. GODDARD. Let me just skip to the third page of the statement. These label requirements are obviously most essential for proper usage and in order to monitor recalls. The concept of a compendium should in no way abrogate such label information. Additionally, the regulations require that— Labeling on or within the package from which the drug is to be dispensed bears adequate information for its use, including indications, effects, dosages, routes, methods, and frequency and duration of administration, and any relevant hazards, contraindications, side effects, and precautions under which practitioners licensed by law to administer the drug can use the drug safely and for the purposes for which it is intended, including all purposes for which it is advertised or represented; and If the article is subject to the new drug, antibotic and insulin provisions-of the Act, the labeling bearing such information in the labeling authorized by the approved new-drug application or required as a condition for the certification or the exemption from certification requirements applicable to preparations of insulin or antibiotic drugs: Provided, however, That the information required by (the above paragraph) may be omitted from the dispensing package if, but only if, the article is a drug for which directions, hazards, warnings, and use information are commonly known to practitioners licensed by law to administer the drug. The information required by this regulation is appropriate and useful. I wouldn't believe that anyone would say that the physician relies on promotional literature in medical journals and publications such as the PDR. As you know, we have instituted several regulatory actions against drugs because of their advertisements, and we are presently requesting four drug firms to issue "Dear Doctor" remedial letters in order to correct PDR monographs. Mr. GORDON. Doctor, can you give us the names of those companies, and also the drugs involved? Dr. GODDARD. Yes. I can give you those now or for the record. Mr. GORDON. Could you read them, and then we will put them in the record, also. Dr. GODDARD. S. E. Massengill, three products: Predsem, Salcort, Salcort-Delta; Organon: Cortrophin Gel, Cortrophin-zinc, Hexadrol phosphate injection, Hexadrol phosphate tabs and elixir; Lakeside Labs, Norparmin. Armour has not been issued, and I would prefer not to mention the drug yet. (The information referred to follows:) STATEMENT OF THE FDA CONCERNING COMPANIES REQUESTED TO CORRECT PDR MONOGRAPHS The three pharmaceutical companies requested to issue "Dear Doctor" letters to correct misinformation occurring in the Physicians' Desk Reference, and the specific drugs involved are: S. E. Massengill Company: Predsem; Salcort; Salcort-Delta. Lakeside Laboratories: Norparmin. Organon, Inc.: Cortrophin Gel; Cortrophin Zinc; Hexadrol Phosphate Injection; Hexadrol Tablets and Elixer. Senator NELSON. Is there approval required by FDA of advertising put in the Physicians' Desk Reference? Dr. GODDARD. No. That is, of course, a form of labeling, and we review it. And if we find flaws there, we then direct the firms to take remedial action. Senator NELSON. But you do not review it prior to publication? Dr. GODDARD. I do not think we should. I think the burden is on the firms. We have explained what the 1962 amendments meant. We are now prepared to explain in even further detail the regulations that we have issued as proposed regulations. And so I do not believe we should have to assume the burden of reviewing prepublication copy. It is quite clear what is required. It should be in fair balance. Physicians should be warned of the bad effects of the drugs as well as told of the good effects. This type of surveillance of advertising coupled with our administrative action will, I believe, substantially increase the quality of such promotions. Nevertheless, advertising will remain advertising. The information contained in package inserts is essential to counterbalance the claims made in many drug promotions. As I have pointed out, these inserts are not accomplishing this function, primarily because it does not reach the physician; secondarily, because it is not in readable form. Now, the compilation of a drug compendium will be a difficult task. The central issue, from FDA's standpoint, is how to abbreviate the package insert material without compromising the public health protection that full information can provide. If we are to condense such labeling, it will still have to adequately reflect current knowledge about the drug. However, we believe that an objective summary, approved by FDA, would be preferable to a package insert which is never read. Also, we believe it will be possible to group several drugs into one category with a general summary covering all the drugs included in the group. 81-280-68-pt. 4- -6 Senator NELSON. Are you satisfied that you have sufficient knowledge, have sufficiently analyzed the problems so that you could, in fact, undertake to develop a compendium in a reasonable amount of time? Dr. GODDARD. I believe it can be done. As I say, the best way to do it is outside of the Government, in my opinion. It is important enough to me that if it is absolutely necessary, then we can do it as a Federal agency. Senator NELSON. You would have to be a cooperating agent, anyway, wouldn't you? Dr. GODDARD. Yes. And I would still prefer, if we had to assume the direct burden, to have much of the work done by contract. Senator NELSON. And supposing the industry decided they would go ahead, they would, of course, work with you? Dr. GODDARD. Yes. Senator NELSON. Do you have any notion, as a practical matter, as to how long it would take to develop and publish an acceptable compendium? Dr. GODDARD. I think about 18 months would be realistic. It is a large undertaking. Of course, I am optimistic. I think we can do it. in that period of time. There are some techniques now available that would lend themselves readily to the production of a volume of this type the computerized storage of information. Of course, as Mr. Goodrich reminds me, and I bring up once again, the NAS summary is now coming to us, and this will be an integral and important part of that task. Senator NELSON. What are those summaries? Dr. GODDARD. These are summaries of their judgments as to efficacy of the drugs marketed between 1938 and 1962. And these represent the opinions of some of the top scientists in the United States who met and discussed drugs that were grouped in 27 categories; 3,000 drugs were involved. Mr. GORDON. Dr. Goddard, when you talk about efficacy, this is not relative efficacy, is that correct? Dr. GODDARD. No, sir. Mr. GORDON. This is merely efficacy as compared to a placebo-better than nothing, is that it? Dr. GODDARD. Well, they are making judgments, sort of putting these drugs in pigeon holes, if you will, of efficacy. There are no doubts about digitalis you see, for example. We have good direct measuring capabilities that say digitalis changes the heart rate, slows up the heart, increases the force of it. So we have good information. And with those that are probably efficacious like digitalis, where there is a body of experience in literature, the firms were given the opportunity to pick the best references that supported their claims for review. And, of course, this is primarily a review of the claims that are made for the drugs, too. So the next category would be probably "nonefficacious" and then "not efficacious." "Efficacious but" is another category. That would refer to trimming back some of the claims that are made, you see. So the judgments are made against the promotional claims the firms have advocated for this particular drug, not relative evidence. Mr. GORDON. But the compendium that we are discussing today is not going to include anything on relative efficacy either, is it? Dr. GODDARD. NO. Mr. GORDON. Well, how is a doctor going to know which is the best drug to prescribe for a particular illness from a relative point of view? Dr. GODDARD. Well, the physician has to make those judgments all the time. And the information contained in the compendium would be a useful guide to him. But there would not be a direct comparison of this product to that product, is the point I am trying to make. Mr. GORDON. And yet the doctors who have come before our committee, who are from the academic field and who are connected with large and important hospitals have stated that the problem of relative efficacy is of extreme importance and should be covered by somebody some place. Dr. GODDARD. Look, efficacy is a function of looking at the drug with respect to the claims that can be supported for it in one sense. Now, this National Academy report and the material that is embodied in the compendium will be restricted as far as claims are concerned-I mean, the claims have to be substantiated. So in that sense, yes, relative efficacy does get into it. But we have to be careful that we do not get in the business of this antibiotic versus that antibiotic, and permit the same claims for both. What we are saying is that the claims have to be substantiated, and thus the physician can draw conclusions about relative efficacy. Senator NELSON. Go ahead. Dr. GODDARD. Another pressing consideration is whether or not the package insert should be completely done away with in view of the compendium, or merely the requirement of distributing it with each package. As complete labeling is the basis of new drug approval, we recommend that such labeling be retained, and additionally, the package insert type of information should remain available for persons, such as clinical researchers, who are in need of more exhaustive data. In a few instances, it probably will not be possible or even desirable to provide for an exemption from distributing the package insert. For example, I mention the biologicals. That information needs to get to the physician for his views at the time of administration. Another factor which prompts our endorsement of the compendium is that it will list all drugs, thereby increasing the physician's prescribing range and, of course, pricing information could be included in a supplement thereby fostering more economic prescribing. However, listing in the compendium should not be construed as governmental approval. As I mentioned before, we are not in a position to guarantee the therapeutic equivalence of all drugs or hence their quality. We are striving toward this goal. And I mentioned, also, the important role the efficacy review being carried out by the Academy will play. Now, with sufficient funds and we estimate about $5 million a year-we could publish such a compendium. We could also provide that listing in the compendium would satisfy the requirements of full disclosure. Although the project could be achieved without increased authority, it would not be the most advantageous manner, in my opin |