15530 CONGRESSIONAL RECORD-SENATE The amendments proposed by the majority members of the Antitrust Subcommittee are the results of a 22-year investigation of the vital prescription drug industry. The tragedy involving thalidomide, horrible though it is, has served the useful purpose of dramatizing some of the abuses in the drug industry and has underscored the urgent need for laws to insure that drugs like thalidomide never get, to the American public. I am glad that the President has pointed up the urgency of this matter. I wholeheartedly agree with him that the Congress should act at once. The Harris bill, like the Senate Judici ary bill, would require several amendments in order to deal effectively with the thalidomide situation and other serious problems revealed by the drug investigation. We have these amendments prepared for introduction in the Senate when S. 1552 is called up. In view of the President's plea for speedy congressional action, let me again point out that S. 1552 is pending on the Senate Calendar, and let me urge the Senate leadership to bring up this bill immediately. If we do nothing-or if we do not write effective legislation-everyone in this country, expectant mothers included, will be courting tragedy with every trip to the medicine chest. NASSAU COUNTY AMERICAN LEGION RESOLUTION ON SUPREME COURT PRAYER DECISION Mr. KEATING. Mr. President, I present, for appropriate reference, a resolution adopted by the Nassau County Committee of the Nassau County American Legion, Department of New York, with regard to the Supreme Court's school prayer decision. I ask unanimous consent that the text of the resolution be printed at this point in the RECORD. There being no objection, the resolution was ordered to be printed in the RECORD, as follows: NASSAU COUNTY AMERICAN LEGION The Nassau County Committee of the Nassau County American Legion, Department of New York, hereby approves and adopts the following resolution: "Whereas the American Legion is dedicated to God and country and by its preamble is committed to defend and uphold the Constitution of the United States, to maintain law and order and to promote peace and good will; and "Whereas the American Legion proudly numbers among its members veterans of every religious faith; and "Whereas Nassau County American Legion believes that the recent decision of the Supreme Court in the so-called 'Regent's Prayer Case' has been widely misunderstood and misinterpreted; and "Whereas said decision has created a state of alarm, anxiety and uncertainty among our citizens which militates against the unity and tranquility of our Nation at a most perilous time in its history; and "Whereas it is incumbent upon all citizens and upon every branch of government, in a spirit of good will and with all possible speed, to resolve the issues created by said decision: Now, therefore, be it "Resolved, That the decision of the Supreme Court is the 'law of the land' and must be complied with; that all citizens study not only this decision but the Constitution it interprets; and be it further "Resolved, That it is the position of the Nassau County American Legion that the law of the 'Regent's Prayer Case' is merely that a State violates the 1st amendment when it (1) writes a prayer (2) sponsors, promulgates and puts the stamp of authority upon that prayer throughout the public school system and (3) authorizes a teacher officially to lead the pupils in the recitation of that prayer and, be it further resolved that it is the position of the Nassau County American Legion that the Supreme Court did no more than to declare that a above procedure; and be it further State may not constitutionally establish the "Resolved, That it is the position of the Nassau County American Legion, therefore, that neither the Constitution of the United States nor the decision of the Supreme Court in the 'Regent's Prayer Case' prohibits our public school children, on their own initiative and voluntarily, praying together a prayer acknowledging our faith in and dependance upon almighty God of their own or their parent's choosing albeit while in school and under the mere technical control and supervision of a teacher; and be it further "Resolved, That it is the position of the Nassau County American Legion that the foregoing alternative method complies with the first part of the amendment which says 'Congress shall make no law respecting an establishment of religion,' and, at the same time, gives full effect to and protects the rights of our children under the second part of the amendment which says 'nor prohibiting the free exercise thereof; and be it further "Resolved, That this resolution be widely promulgated for the information and guld ance of all citizens and divisions of our Federal and State Governments concerned herewith to the end that the right of our children freely to exercise religion while in school under the foregoing method might be implemented without delay in the public schools of the State of New York." ROTC PROGRAMS Mr. KEATING. Mr. President, the requirements of national defense necessitate the maintenance of adequate ROTC facilities at our colleges and universities. Faced with ever-increasing student enrollment, many of our institutions, both public and private, are finding it more and more difficult adequately to meet this need. Because the ROTC is in effect a part of our overall defense program, and because of the pressures of enrollment in our colleges, the executive cominittee of the Association of NROTC colleges has recently adopted a resolution calling for the endorsement by Congress of Federal financial support for the establishment of an expansion program and the development of physical facilities for ROTC instruction at both private and State universities and colleges. Mr. President, I ask unanimous consent to have included in the RECORD at this point the resolution adopted by the executive committee of the Association of NROTC colleges, forwarded to me with the endorsement of the University of Rochester. August 3 There being no objection, the resolution was ordered to be printed in the RECORD, as follows: Whereas the requirements of national des fense necessitate the maintenance of adequate ROTC facilities in training at universities throughout the United States; and Whereas the increasing pressure of student enrollment taxes the resources of private and public institutions to meet the demands made upon them to provide adequate facilities for officer training: Therefore, be it Resolved, That the Senators and Representatives from States in which ROTC facilities exist be requested to actively advocate and support legislation directed toward complete Federal financial support of the establishment expansion program and development of physical facilities for ROTC instruction at private and State universities and colleges in order that the essential training of military ofcers may be adequately and emciently advanced; and be it further Resolved, That coples of this resolution be forwarded to the Members of the Senate and House of Representatives concerned and to the Chairman of the ROTC Advisory Committees of the Department of Army and Air Force; and Whereas it appears that legislation providing for ROTC facilities has been shelved: be it further Resolved, That the Department of the Navy be requested to push for action on the part of the Department of Defense in behalf of such appropriations. THE SOVIET OIL OFFENSIVE Mr. KEATING. Mr. President, as we all know, the United States is now engaged in a cold war economic rivalry with the Soviet Union. This rivalry involves many factors, and includes both maintaining and increasing the economic strength of the Western bloc of nations, and promoting the economic development of the emerging nations. One part of this struggle involves competition in such crucial items as oil No one needs to be reminded of the great economic and strategic importance of oil and oil products. It is vital that the free world should sustain its dominant position in this market, and that it use these oil products and the revenues therefrom to develop the economies of the countries in which the oil is found. Recently there has been increased competition in this field from Soviet oil interests. They are slowly wedging their way into markets ordinarily controlled by Western oil companies, and are receiving contracts for oil prospecting and refining in countries where similar Western concerns are already well established. This competition is politically motivated on the part of the Soviet Union, which sets prices without regard to costs in order to undermine private enterpi'se. Mr. President, testimony just yesterday before the Finance Committee on the trade expansion bill pointed up the dangers of the Russian oil offensive. There is a real need for Government cognizance of the threat and for official action. For that reason, it is a matter of gravest concern to me that a vital report, prepared by the National Petroleum Council and the Interior Department, has been completely blocked by a 15686 CONGRESSIONAL RECORD Mr. CHAVEZ. To me this is not a Republican or a Democratic project; it is an American effort. Mr. ALLOTT. That is entirely correct. I appreciate the Senator's statement. So far as Colorado, New Mexico, and the other Western States are concerned, I know that those in the Middle West and elsewhere complain about their using water to grow more food. The people in New Mexico complain; they say that the Mountain States cannot produce food as well as New Mexico can. Let me tell my good friend, the Senator from Colorado, the history of the Rio Grande irrigation project in New Mexicc and Texas, and also the history of the Elephant Butte project, and the history of the El Paso Water and Improvement District, in Texas. The average production of cotton in the Deep South is 370 pounds an acre. But in the irrigation districts in New Mexico, Texas, Arizona, and California, it is as much as four bales or 2 000 pounds-an acre. That shows what irrigation does. Mr. ALLOTT. The Senator from New Mexico is entirely correct, and I appreciate very much his kind remarks. Once again, in the area of new drug legislation, the President has taken the initiative. He has renewed his sound appeal of April, in which he recommended to the Senate substantial strengthening of existing drug statutes. The President's statement greatly increases the likelihood of the adoption of adequate amendments to present drug statutes. We shall, thereby, close intolCrabic loopholes in the law. Today, the President has submitted to the Senate a number of amendments designed to strengthen S. 1552. The Nation also welcomes the encouraging demonstration that our new Secretary of Health, Education, and Welfare, Anthony Celebrezze, has promptly mobilized his Department to carry out the President's program. FAVORABLE REACTION TO SUBCOMMITTEE It has been personally gratifying to me to note the prompt, enthusiastic response from all parts of the country to the hearing of the Senate Government Operations Subcommittee on August 1. Our subcommittee, I may say, has only begun its efforts to bring to light certain conditions and problems which have long concerned us. These conditions and problems, so grimly illustrated by the thalidomide tragedy, are part of an international, a national, and a governmentwide pattern, involving almost all scientific research. nesses I refer, of course, to critical weakin scientific information and communication. This is the undramatic story behind the dramatic thalidomide tragedy. Information and communication deficiencies represent the SENATE hidden culprit responsible for innumerable scientific administrative flaws. THE HUGE FINANCIAL STAKE IN RESEARCH For 4 long years, I have urged the Federal Government to coordinate the information generated by its scientific research. In the 1962 fiscal year, the Federal Government is spending 1 out of every 9 budget dollars--$10 billion for scientific research, development, testing, and evaluation. In the 1963 fiscal year, it will spend $12 billion for this purpose. Perhaps as many as 160,000 federally financed projects are now underway in the 50 States and overseas. Amazingly enough, there still is not available as of today, any systematic means whercby even the President of the United States could secure prompt, reliable, comprehensive information as to all the research which is now in processor which has been completed-in any one of a dozen broad, major headings. To identify all the research, even the President, or his able Director of the Office of Science and Technology, Dr. Jerome Wiesner, would have to and does have to ask each Federal agency to compile its own information in its own way— at its own speed-with its own varying definitions. There is really no Government-wide information system. There is no real system of separate agency systems. There is only a patchwork, a hodgepodge. This is true of interagency drug research. It is true of interagency space science and military research. Agency information systems do exist and by the dozens. They vary from "excellent" in the case of, say, the Atomic Energy Commission to "average," "poor" or "awful." - For 4 years. I have urged reform. I have often felt somewhat like a voice crying in the wilderness. At long last, some reforms are beginning to be made, but, invariably, at a pitifully slow rate. One would think the Federal agencies felt they were doing Congress a favor by adopting information reforms. These reforms are actually for the agencies' own good. But they do not seem to view improvements that way. They offer every conceivable excuse for delay and inaction. AGENCY PACE OF A "TRANQUILIZED TURTLE" In the subcommittee's approach to these agencies, we have been exceedingly tolerant and patient. We held hearings in 1958 in which we urged them to reform. We held a hearing in 1960 in which we did likewise. In between and thereafter, we sent a stream of letters, memoranda, mimeographed, and printed reports. We urged; we pleaded; we implored reform. The agencies, particularly the Department of Health, Education, and Welfare, have made only limited halfhearted response. They are proceeding with the pace of a tranquilized turtle. There is little sense of urgency: there is little interagency teamwork; there is endless buckpassing. SIRUPY GOVERNMENT COMMITTEE REPORTS Dr. Wiesner has fortunately empaneled an information group of private August 6 experts under the President's Science Advisory Committee. Its report will be out in a few months. I have been hoping and expecting meanwhile a report from an interagency career group, the Federal Council for Science and Technology, as regards the information problem. It remains to be seen whether this Council report will be the same "standard sirup" such as usually emerges from Government committees. ACTION REGARDING APPROPRIATION REPORTS Meanwhile, this year, I started a new effort. I have gone down the line-appropriations subcommittee after subcommittee-to urge that appropriation reports contain mandates for reform. Two My appeal has been heeded. such reports, on health and defense, do fortunately now contain such mandates. I intend to make sure that the agencies are called to account during the 1964 fiscal year appropriation hearings for what they have or have not done by that time. MESSAGE OF AGREEMENT FROM PHARMACEUTICAL MANUFACTURERS ASSOCIATION Now, let me turn to the August 1 hearing and its significance in relation to drug research information. For a reaction to the hearing, I should like to quote but one of many sources which promptly and graciously communicated with me thereafter. I refer now to a fine message from Dr. Austin Smith, president of the Pharmaceutical Manufacturers Association. That same day, August 1, Dr. Austin Smith wrote to me. He expressed agreement with a series of statements which I made at the hearing, that is, on the need for improvel coordination and communication among agencies of the U.S. Government, between American and foreign agencies, American and foreign drug companies, American and foreign researchers and practitioners. Dr. Smith likewise expressed agreement with the view which I suggested on the need for systematizing "increased safeguards," so as to reduce the degree of risk which will always, to some extent, be present. Dr. Smith advised that: The subject matter of your hearings deserves examination and discussion throughout the world. He stated, therefore, that he istaking steps immediately to provide the public record of your subcommittee to the headquarters of associations of the pharmaceutical industry elsewhere in the world. I am very gratified to receive word of this splendid action. It is clear that all of us face, in the information and communication problem, a common challenge which merits the best effort of all interested parties. The medical profession, the pharmaceutical industry, the pharmaceutical profession throughout the world have everything to gain and nothing to lose from strengthening communication on drugs in the interest of better health for mankind. I ask unanimous consent that the text of Dr. Smith's letter to me be printed at this point in the RECORD. 1962 CONGRESSIONAL RECORD - -SENATE There being no objection, the letter was ordered to be printed in the RECORD, as follows: PHARMACEUTICAL MANUFACTURERS ASSOCIATION, Washington, DC., August 1, 1962. The Honorable HUBERT H. HUMPHREY, Chairman, Subcommittee on Reorganization and International Organizations, Committee on Government Operations, U.S. Senate, Washington, DC. DEAR SENATOR HUMPHREY: Permit me to comment on statements which you made this morning in connection with the hearing conducted by your Subcommittee on Interagency Coordination in Drug Research Information. You stated that there may well be serious problems of lack of coordination and communication among agencies of the US. Government, and between American and foreign agencies, American and foreign drug companies, and American and foreign researchers and practitioners. Speaking for the member prescription drug humans, with maintenance of complete records. Second. A broad-scale, interagency and intra-agency cooperative effort in drug research, to include thorough reporting of drug reactions in the Federal Government's three hospital systemsVeterans' Adininistration, Department of Defense, and the Public Health Service. Third. An educational campaign by the Public Health Service, cooperating with medical organizations, to caution physicians and patients against casual, needless use of drugs, particularly on the part of women of childbearing age. Fourth. Establishment of a medical and drug research information center, under the auspices of the U.S. Public Health Service. At this center, public information and. to the extent that proprietary rights may permit, private information should be gathered, recorded, manufacturing firms of this association, I indexed, evaluated, and made available agree with those statements. Further, in commenting on the fact that the thalidomide problem has been prevented In the United States, you stated a need to systematize increased safeguards and to reduce the degree of risk which will always be present to some extent. You also stated that both Government and private reviewers and investigators must be given better, prompter, more reliable access to the world's medical literature, in all principal languages. Again, I agree with those statements. Repeated, continuous and sometimes costly efforts by the U.S. pharmaceutical industry to help solve some of these serious problems are well known in scientific circles. For example, in 1958, through its association, the industry began a pilot study of mechanical indexing and retrieval of literature references to steroid compounds. In 1961, after expenditure of 835,000, the project was turned over to the U.S. Patent Office, which had been kept advised of its results. In addition, the Scientiac Literature Committee of the PMA Research and Development Section, composed of leading industry scientists, has worked with the National Science Foundation for a number of years in the latter's continuing assignment to expedite indexing and retrieval of scientific research information within the U.S. Government. In my judgment you are to be commerded for your renewed approach to a matter of prime importance in today's climate of rapid scientific advances. The subject matter of your hearings deserves examination and discussion throughout the world. With this in mind, I am *aking steps immediately to provide the public record of the proceedings of your subcommittee to the headquarters of associations of the pharmaceutical industry elsewhere in the world. Sincerely yours, AUSTIN SMITH, M.D. AN ACTION PROGRAM TO PREVENT Mr. HUMPHREY. Mr. President, we need bold national and international action programs so that a thalidomidetype tragedy will never recur. I speak of the tragedy of malformed babies resulting from the use of a drug. I should like to suggest a five-point program for this purpose: First. Enactment of an amendment to assure thorough control of investigational testing on humans by the Food and Drug Administration. The amendment should require adequate testing of drugs on laboratory animals prior to testing on to pharmaceutical manufacturers, doctors, and hospitals. The center should, in effect, be the central station of a network of centers. It should be able to draw upon and contribute to Federal inhouse and extramurally supported centers, as well as other public and private resources-medical, pharmaceutical, and others. Fifth. On the initiative of the United States, an international request to the World Health Organization to provide for exchange of up-to-the-minute information on drugs between the United States and other governments, as well as with the healing arts professions of the respective nations. INCREASED FEDERAL COORDINATION Since the Committee on Government Operations, is, per se, interested in efficient Federal activities, we will continue to insist upon the Federal Government putting its own "drug information house in order." Up to now there has been a shocking lack of coordination within and between U.S. agencies on drug information. Throughout the executive branch, we need faster, more complete, better indexed, and evaluated information. We also need a stronger overall drug law-particularly for experimental drugs stronger food and drug regulations, and more aggressive FDA administration of the regulations. HAZARDS TO FREGNANT WOMEN Priority must be given to improvement of information coordination on drugs intended for pregnant women. Aside from Dr. Frances Kelsey's courage and vision and a few other cases, the Food and Drug Administration does not appear to have been aggressive in protecting the unborn. Genuine miracle drugs have contributed immeasurably to maternal and child health, but adverse effects are often suspected and must now be thoroughly explored, and suitable safeguards taken. The Food and Drug Administration should request a report, as soon as feasible, from the National Institutes of Health on drug-related findings in 23,000 pregnancies, now being studied in a nationwide project.. 15687 The principal damage to the central nervous system of an unborn baby apparently occurs during the first few weeks after conception. It is during this time that the woman herself may not know she is pregnant and for trivial reasons may be taking drugs which could affect the child. It will take unprecedented international teamwork and research to unlock the mysteries of whether, how, and why certain so-called harmless drugs do affect pregnancies. SUPPORT OF KEFAUVER AMENI MENT ON ANIMAL TESTING The Senator from Tennessee [Mr. KEVAUVER] is proposing an important amendment for thorough animal testing of investigational drugs, prior-I emphasize, prior-to testing on humans. I strongly support the principle of this amendment. I urge that it include thorough testing en pregrant laboratory animals particularly large animals-not only rats or mice wherever and whenever there is likelihood that pregnant women may ultimately use the drug. Let me make this point clear. I propose that a vast spectrum of drugs, which may or may not be intended for pregnancy, but which may be regarded as likely to be used by pregnant womenthat is, for headaches, insomnia, and so forth-should be thoroughly tested on pregnant laboratory animals. Of course, even if there is the most thorough testing of investigational drugs on pregnant animals, there is no assurance that the results will prove applicable to human beings. Nevertheless results of such animal tests could alert general practitioners, obstetricians and pediatricians to possible dangers. Then, too, when the investigational drug is judged ready for testing on humans, such testing should be on a phased ing on needlessly large populationsbasis. This would avoid premature test male or female, adult or child-before results became available and were evaluated from smaller human samples. JUSTIFICATION FOR ANIMAL TESTING Let me note at this point a documentated justification for the overall amendment and for my stress on tests on pregnant animals, in particular. First. Louis Lasagna, M.D., division of clinical pharmacology, Johns Hopkins University, stated on July 19, 1961 (hearings, Senate Judiciary Subcommittee, on S. 1552, 87th Congress, p. 1083): ... present FDA prerogatives do not satisfy me with regard to toxicity either. It is shocking that experimental drugs are subject to no FDA regulation of any sort before patients receive them. Some drug houses perform extensive animal tests before a drug is first put into man; others perform almost none. It is reprehensible for man to be the first experimental animal on which toxicity tests are run, simply because bypassing toxicity tests in laboratory animals saves time and money. Section 2. On July 25, 1961, Dr. Lasagna wrote to the subcommittee-hearings, ibidem, pages 973-974-and I ask unanimous consent to have extracts from the subcommittee hearings printed at this point in the RECORD. 15688 CONGRESSIONAL RECORD SENATE There being no objection, the extracts were ordered to be printed in the RECORD, as follows: (1) At present, the Food and Drug Administration has essentially no jurisdiction over experimental drugs until a new drug application is filed. This leaves the decision as to the nature and extent of animal toxicity tests performed prior to human testing up to the drug house (or other proponent of the drug) and, to a lesser degree, to the clinical investigator who is to put the drug into man. (2) The variation between drug houses in preclinical toxicity testing is tremendous. I have been approached to start human testing of a drug with the only information available being the amount of drug required to kill 50 percent of mice receiving the drug in one intravenous dose. In contrast, it is not infrequent to have a firm supply toxicity Information on a proposed drug which runs to many pages in length. The toxicity tests recommended by such experts as Dr. Lehman of the Food and Drug Administration in this country, and Drs. Paget and Spinks of the Imperial Chemical Industries, Ltd., in England, are not infrequently lacking in the toxicity data sent to us by pharmaceutical firms. (3) Although enough acute animal toxicity data may be available to justify short-term experiments in man, there are often unavailable at the start of human testing adequate chronic toxicity data in animals. This leads to chronic toxicity tests being performed in man first, since for many disease states the repeated use of the drug must be investigated. Clinicians who are impressed by the effect of one or two doses of a new drug will often start chronic administration of the drug, even when the drug has not been cleared for ruch prolonged human trials by the drug houses supplying the agent. phenomenon is well known to the industry. This (4) It is, according to FDA officials, e not uncommon occurrence for new drig applicaMons to be led with extensive clinical data included, but without adequate supporting animal toxicity data being simultaneously available. In fact, it has been mede a matter of public record that drugs have been cleared for sale on the market with chronic toxicity tests still pending. It is easy to understand why drug houses are reluctant to spend the considerable time and money involved in routine toxicity testing unless the drug shows "promise," ie., until the first human tests are encouraging. It is also, for reasons described above, easy to understand why human testing can "get shead" of animal testing. In my opinion, therefore, a minimal amount of toxicity testing should be required by law before & drug ever gets put into man. There are, I suspect, other reasons for Inadequate animal toxicity tests besides those mentioned above. Drug houses vary greatly in the caliber of their staffs. Some have excellent pharmacologists, toxicologists, and pathologists, whereas others are deficient in these regards. Therefore on occasion it is likely that poor judgment and ineptitude also enter the picture, instead of (or in addition to) pressures for speed and accuracy. The very existence of the broad discreparcies in toxicity testing described above testify to a troublesome state of affairs. Are the drug houses who perform extensive toxIcity tests before ever going to man merely overcautious conservatives? I think not. Predicting human toxicity is by no means a simple matter, but it is preferable to take all reasonable steps to escape untoward reactions in man that could be predicted from animal work. Somewhere between the extreme care and effort suggested by some pathologists and the inadequacies of the worst of the preclinical evaluation now be ing done in this country lies a reasonable Mr. HUMPHREY. Third, Mr. Presi- Until recently, no thought has been given to the need for the testing of drugs for potential harmfulness to the human embryo. Fourth. Senator KEFAUVER has stated in a letter of July 31, 1962, to several Members of the Senate: The most tragic aspect of the entire thaildomide history is that, had such studies been made, the horror could have been averted. This is proved beyond doubt by studies of rabbits by the British seller of the product, Distillers Corp., made unfortunately after the drug had been widely used in humans and after it had been identified as the cause of the malformed infants. Reporting in the English medical journal, the Lancet, April 28, 1962, Dr. G. F. Somers notes that experiments in rats showed no malformstions but that, "Now we have succeeded in producing deformities in rabbits remarkably similar to those seen in humans." More than half of the litter of the mother rabbits given thalidomide were born deformed. None of the litter of the control rabbits, that is, those of the same colony not given thalidomide, were born deformed. Dr. Somers goes on to state, "No deformities of this kind have been previously observed in the colony, involving the breeding of over 1,000 progeny, and our chief animal technician, Mr. R. E. Hughes, states that he has never seen anything like this during 50 years' experience of rabbit breeding." Fifth. I am reprinting in the Government Operations Subcommittee hearing various pertinent exhibits on this subject, including the following article from the journal, Pediatrics, which I ask unanimous consent to have printed at this point in the RECORD. There being no objection, the article was ordered to be printed in the RECORD, as follows: [From Pediatrics, October 1961] (Statement by Committee on Fetus and It is a basic premise of pediatrics that Existing drugs and agents that are developed in the future for use in the fetus and in infants must be subjected to more extensive preclinical investigation than is being carried out at the present time. The pharmacologic responses of the immature human may differ greatly both quantitatively and qualitatively from those of the adult. As a result, data obtained from tests in mature animals and human adults or older children cannot be accepted as a satisfactory basis for recommendations concerning the fetus and infant. The pharmacologic properties of drugs should be studied in vitro and in vivo in the tion August 6 species. Of particular importance would be a knowledge of the LD. dose responce, metabolism, and distribution and disposiof the drug. These Geterminations should be performed in two or more animal species (a rodent and nonrodent species). Pharmacodynamic actions and clinical effects of drugs in humans should be assessed in clinical situations in which they may be useful. In order to pursue these principles, it is recommended that drug labels should specifcally indicate the extent of existing information concerning the use of the agent in the fetus and the infant: When there have been no pharmacologic studies of a drug in immature subjects, an explicit statement of this fact should be indicated on the drug label or in a readily available package leaflet. Physicians who administer drugs to the fetus and the infant must be alert to unusual effects in this subdivision of the human species. William A. Silverman, M.D., Chairman; MY EFFORTS FOR PERINATAL RESEARCH On December 1, 1958, I discussed this subject with Premier Nikita Khrushchev in Moscow. At that time, I urged a U.S.U.S.S.R. partnership in finding the answers to the mysteries of how life develops and how so often and so tragically it emerges with defects. In the years which have followed, I have been a strong supporter of the perinatai collaborative research project, as supported by NIH. This project is the greatest effort of its kind ever made in medical history. I want every U.S. agency and every doctor to gain the greatest insight which may become available through this project. Meanwhile, in my judgment, evidence gained at the hearing and other evidence which the subcommittee has compiledbut which we have not yet presenteddemonstrates that there is an imperative need for a massive Governmentwide effort to reduce to an absolute minimum whatever drug dangers now exist or may in the future develop to pregnant mothers and unborn babies. Laboratory animals must be utilized; they inust be utilized first; and they must include larger animals-not just rats and mice. I am neither a physician nor a pharmacologist. I am a pharmacist, and I do not presume to have an expertness on issues of toxicity to animals. Even the greatest experts caution as to applicability of animal findings to human findings. I do know, however, that it is best to observe every reasonable safeguard before permitting testing on tumans. 1962 THE MANY POINTS WHICH THE HEARING CONFIRMED CONGRESSIONAL RECORD - SENATE The hearing which we conducted on August 1 established, I believe, a great many points which bear followup on the part of the executive branch, the drug companies, and the international scientific community... At the start of the hearing, it may be recalled, I issued a public statement in which I indicated certain tentative observations. I pointed out that confirmation of these observations would await upon the receipt of definitive proof. In every single instance, I believe, that proof was received. The hearing has, I believe, strengthened the basis on which the Congress can now proceed to examine the legislation which has been so carefully explored in the Senate Judiciary Subcommittee on Antitrust Activities, as headed by the distinguished Senator from Tennessee [Mr. KEFAUVER]. I ask unanimous consent that there be printed, at this point in the RECORD, a memorandum in which I have listed those tentative judgments on which I had commented prior to the hearing, and which were subsequently confirmed. In this memorandum, I cite the verbatim questions and answers from particular pages of the unedited transcript of the hearing. There being no objection, the memorandum was ordered to be printed in the RECORD, as follows: MEMORANDUM BY SENATOR HUBERT H. HUMPHREY SHOWING THE CONFIRMATION BY THE AUGUST 1 SUBCOMMITTEE HEARING OF TENTATIVE JUDGMENTS WHICH HAD BEEN EARLIER FORMULATED AND SUBMITTED Tentative judgment: There is inadequate communication and coordination between Federal agencies. Confirmation: The hearing confirmed the Inadequacy of communication and coordination in an appalling number of respects. Let me cite just a few: 1. Dr. James Shannon, Director of the National Institutes of Health, confirmed the lack of a systematic, inter-Institute drug information research system upon which FDA could draw and which, in turn, could contribute to FDA. 2. Dr. Shannon confirmed that only three of the seven NIH categorical Institutes maintain even partial drug information research systems within their own organizations. Page 102: "Senator Humphrey. I would like to ask, Ras the Public Health Service, and particularly the National Institutes of Health, established a centralized; coordinated system for handling research information on the many hundreds and thousands of drugs that are seeking a place in the market? "Dr. SHANNON. We have not, sir-except in those areas that we are except in those areas that we have accepted as more or less specific responsibility for development." Page 105: "Senator HUMPHREY, NOW, doctor, I understand that there is no comprehensive system of handling research information in the National institute of Allergy and Infectious Diseases. Yet literally hundreds of drugs have adverse allergic effects. "Dr. SHANNON. That is correct, sir." Page 107: "Dr. SHANNON. Senator, fundamentally. Senator HUMPHREY, I am as unhappy as you are about the situation. But I would emphasize that it is not a simple problem that will find simple solutions.” 3. Dr. Frank Rogers, Director of the National Library of Medicine, confirmed (p. 130) that he had not consulted with the Food and Drug Administration in preparing the plans for the Medical Literature Analysis and Retrieval Service, known as MEDLARS, which will become operational in September 1963. He said, page 129, "We cannot consult with everybody." No one asked him to consult with "everybody." There was definite reason, however, for him to consult with an agency in his very own Department which has a vital stake in the National Library's output, namely, the Food and Drug Administration. 4. The Food and Drug Administration was unable to indicate (p. 132) why it did not register research projects with the Science Information Exchange. Two years ago, it promised the subcommittce to do so, at least with respect to nonconfidential projects. Why did it not keep its promise? When does it expect to cooperate with other Government agencies in this exchange? Does anybody in the executive branch care whether FDA or other agencies cooperate with the exchange? 5. Food and Drug Administration officials confirmed (p. 49) that their Adverse Drug Reaction Reporting System included only 44 of the Nation's 6,000 hospitals. This includes only 8 of the 15 Public Health Service hospitals; none of the Veterans' Administration hospitals; none of the Department of Defense hospitals. Why, I ask? The absence of formal Veterans' Administration participation is, I might add. particularly distressing. VETERANS' ADMINISTRATION'S OTHERWISE EXCELLENT RECORD I should like to make it perfectly clear that the Veterans' Administration has, in many respects, an excellent record of research cooperation with other Federal health agencies. The Veterans' Administration clearly recognizes its responsibility and opportunity for the most careful type of clinical testing. It was Veterans' Administration-Department of Defence testing of drugs which has produced so dramatic a decline in TB incidence. and, as a result, in the number of TB hospitals and TB beds. There is excellent cooperation in cancer chemotherapy programs between VA and National Cancer Institute. The Veterans' Administration now has 171 hospitals with 112.000 patients as well as 94 clinics. These represent a controlled population which offer opportunity for rigorous "double-blind testing, such as is not available and is not practiced in a great deal of investigational testing supported by pharmaceutical companies through individual cliniclans. The Veterans' Administration hospital system offers unexcelled opportunity for lifetime followup of patients. We, in the United States, fortunately, have the finest program of medical care for exservicemen in the world. It is extremely unfortunate the VA has marred an otherwise outstanding record by a failure to follow through with the Food and Drug Administration. Initial discussions were held in 1960 between VA and FDA for formal participation in the latter's adverse drug reaction reporting program. The arrangements regrettably floundered over the issue of lack of an FDA budget to cover expenses for VA participation. 15689 I am hopeful, however, that neither this nor any other "reason" fil prevent VA participation in this program on a formal and systematic basis in the future. NO LIAISON BETWEEN NINDS AND DA (6) Food and Drug Administration officials confirmed that they had had no contact with the perinatal collaborative research project now being conducted by the National Institute for Neurological Diseases and Blindness with 15 hospitals across the Nation. This project ofers a golden opportunity for systematic understanding of, among other phases, the relationship. if any, between drugs, pregnancy difficulties, pregnancy wastage, congenital defects, and related prob lems. But regrettably, the National Institute for Neurological Diseases and Blindness, in turn, has had no plans for systematic output to the Food and Drug Administration. It should be noted that the vast perinatal collaborative research project has been one of the most difficult programs ever to be attempted. It is still too early to draw any definitive conclusions, based upon the initial pregnancies, registered with the cooperating hospitals. Only relative crude data is available, and it must be analyzed in greatest detail by NINDB's scientific advisers. The fact, however, that there was appar ently no forethought of cooperation between FDA and NINDB is, to say the least, unfortunate. I have urged Commissioner Larrick to request NINDB to make available initial results as soon as NINDB's scientific panel feels that some judgment can be expressed. In addition, I am urging the strongest collaboration between NINDB and an American Medical Association's research project, analyzing birth experiences in hundreds of thousands of cases. It seems clear that inanitely more can be learned and should be learned from birth statistics in the 50 States and abroad. The birth certificate itself should contain, in all the States, information as to congenital malformations. In that way, medical science would be able to spot promptly both longtime or epidemic-type dangers to the birth of healthy babies. The Director of NINDB, Dr. Richard Masland, is a world renowned authority on mental deficiency, a has publicly referred to possible relationships betweeen chemical agents and congenital defects. See for example his comments on The Discovery of Teratogenic Agents" in The Prevention of Mental Retardation-Part II." a survey. sponsored by the National Association for Retarded Children, Journal of Diseases of Children, volume 95, January 1958, No. 1. LACK OF INTERNATIONAL COORDINATION Tentative judgment: There is inadequate international communication and coordina tios of information with respect to new drugs. Confirmation: The hearing confirmed a wide array of gaps with respect to informa tion on new and old drugs on the world |