departments in the light of advice from their scientific staffs and from competent impartial clinical investigators, and (3). that they revise their advertising methods. Advertising should not be premature; advertisements for a new drug should not appear before a single clinical article is published in a reputable medical journal. Advertisements should be in keeping with the dignity of the industry from which they come and the good sense of the profession to which they go. The time is already past due for reputable manufacturers to establish a code of ethics for advertising and abide by it. When this has been done the words "ethical manufacturer" will mean a manufacturer who works for the good of the public rather than meaning, as at present, one who advertises only to the medical profession, no matter how he advertises. The regulatory agencies of the Government function as impartial judges for the benefit of the consumer. Laws always lag behind actuality, and budgets are always deficient; but in spite of these limitations the regulatory agencies deserve great credit for keeping the present system from getting out of hand altogether. How can they do the job better? Certainly they should insist upon honest and thorough investigations by clinical investigators. They should inquire how the cases were obtained for trial; were they selected out of a larger number of cases and, if so, by what criteria? Funds should be available to them for financing tests of drugs when the evidence submitted is equivocal or unconvincing. They should also be able to employ consultants to advise them in difficult cases. These agencies need the strong backing of the medical profession; the patient's welfare must be kept continually before them so as to counteract the obvious pressures from the pharmaceutical industry. Many people believe that the laws should be amended so that the Food and Drug Administration can pass on the efficacy of a drug. At present, except in the case of the drugs that are certified, which include insulin and certain antibiotics, the Food and Drug Administration cannot prohibit the sale of an ineffective drug; its only recourse is to seize the drug as misbranded if a therapeutic effect is claimed in the circular that accompanies the package. This seems a roundabout way to protect the public. In Furthermore, the present laws leave all advertising, except that which accompanies the package, to a separate agency, the Federal Trade Commission. spite of the excellent cooperation that exists between the two agencies, this is a cumbersome method which has not succeeded in giving adequate protection to the patient. Many people believe that the law could be enforced more efficiently and more completely if advertising as well as labeling were regulated by the Food and Drug Administration. My suggestions can be summarized in two words: "information" and "regulation"; prompt and exact information for the practicing physician from the investigator, the professional societies, the medical journals and the specialty groups; willingness on the part of capable investigators, teachers, and other leaders in medicine to spend time in spreading the truth about drugs; probity and sanity on the part of the manufacturers in keeping advertising factual rather than suggestive, direct rather than irrelevant, truthful rather than misleading; recognition on the part of the practicing physician that his is the final responsibility for the use of a drug and that he cannot give this decision over to anyone else. Regulation there must be for those who will not work from higher motives; regulation by industry to the extent that it can be done; regulation by organizations of physicians where they can help, and regulation by Government where the others fail to do the work. Let those who object to the third alternative strengthen the first two. These things should be done; these things can be done; shall we here agree that these things will be done? In the words of George Washington, "Let us raise a standard to which the wise and just can repair.” NOTE.-Research and Educational Hospitals, University of Illinois, 840 South Wood St. (12). This paper is being published simultaneously in the AMA Archives of Internal Medicine. EXHIBIT 13 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, Hon. JOHN A. BLATNIK, Chairman, Subcommittee on Legal and Monetary Affairs of the Committee on Government Operations, George Washington Inn, Washington, D. C. Dear Mr. BlaTNIK: In an effort to present all of the pertinent facts to you and the other members of the committee, I welcome this privilege of submitting additional information by letter for your consideration. In my testimony which ends at the middle of page 338 of the transcript, my final sentence is as follows: "So out of our 8 budgeted positions for New Drug Division, we have but 5 filled and 2 of those represent 4 half-time men." I should like, with your permission, the record to show an additional statement as follows: Mr. Chairman, we have 5 physicians in our New Drug Branch whereas, in my judgment, ideally in terms of responsibility and current workload, I believe we should have perhaps as many as 12 or 15. While this may appear as an excessive increase, careful analysis of the situation does not support such a conclusion. For example, a considerable amount of literature research is necessary on the part of these individuals if they are to maintain an intimate and up-to-date medical knowledge of their respective fields and specialties. These individuals need more time for firsthand discussion with clinical investigators and attendance at research and medical meetings, so that they are aware of all of the latest work and current thinking of informed experts in medicine. Ideally, our new drug physicians should not have to work continuously under the pressure of the statutory time limit. While I appreciate the value of pressure and urgency in getting a job done, I nevertheless feel that continuous pressure without time for reflection or introspection inevitably leads to decreased awareness, if not frank dulling of the wits. Under such circumstances I think you will agree with me that inadvertent, but nevertheless, serious errors are apt to become more likely. Also, in my testimony at the bottom of page 338 and at the top of page 339, I have indicated that there are at least two factors which hamper our recruitment of physicans for our New Drug Branch. They are the unusual degree of scientific competence required of these people and the salary limitations which exist for these positions as currently allocated. Having given serious consideration to this problem during the past 4 years, I firmly believe that the interest of the public can best be served by seeking excepted appointments for our new drug medical personnel, so that men of recognized scientific achievement can be attracted and retained in this work. You are aware, I am sure, that many other governmental agencies have successfully resolved this problem by obtaining excepted appointments which pay up to $19,000 per annum for their senior scientific personnel. The Public Health Service, Atomic Energy Commission, Department of Defense, Department of Commerce, the Veterans' Administration, the National Science Foundation, and several other agencies as well, all are able to recruit and compensate their scientific leadership because of this advantage. I believe that the operations of the New Drug Branch are so critical in terms of human health that we can well justify an effort to place this entire group in excepted appointment positions. Further support for this point of view is contained in the Citizens Advisory Committee Report of 1955 which recommended “The stature, prestige, and salaries of the professional personnel who must bear the burden of passing on new drugs should be increased" (p. 42). I am enclosing a copy of this report for your information and perusal. In addition, there are several other key scientific jobs in the Food and Drug Administration, particularly in our Bureau of Biological and Physical Sciences which, in my judgment, deserve the same consideration. 1 Sincerely yours, ALBERT H. HOLLAND, Jr., M. D., Medical Director. EXHIBIT 14A Facts Needed to Assess Public Health and Social Problems In the Widespread Use Of the Tranquilizing Drugs Morton Kramer, Sc.D. PUBLIC HEALTH MONOGRAPH No. 41 227 Introduction The purpose of this monograph is to describe the large variety of scientific facts needed to assess the public health and social problems that may result from widespread use of the tranquilizing drugs (chlorpromazine, reserpine). From a review of several recent reports on the subject (1-3), it is quite clear that these drugs are being used in persons of all ages to treat not only a wide spectrum of psychiatric disorders but also hypertensive vascular disease and many other conditions. In addition, reports suggest that the tranquilizing drugs are being widely used as sedatives in place of the barbiturates. The tranquilizing drugs have been heralded in public affairs pamphlets (4) and in various periodicals as opening a new era in psychiatry. To quote from an article in a recent issue of Time (5): The treatment of mental illness is in the throes of a revolution. For the first time in history, pills and injections (of two inexpensive drugs) are enabling psychiatrists to (1) nip in the bud some burgeoning outbreaks of emotional illness, (2) treat many current cases far more effectively, and (3) in some instances reverse long-standing disease so that patients can be freed from the hopeless back wards of mental hospitals where they have been "put away" for years. That these drugs are a potential force for much good and can open a new era in psychiatry, no one will deny. But, on the basis of the evidence available in the medical literature to date, we should also be aware (a) that there is a lack of data obtained from well-controlled studies which would permit us to assess the significance of many of the results reported, (b) that some of the facts reported with respect to complications indicate that these drugs are a potential source of danger, and (c) that there is a lack of well-designed followup studies that would permit the assessment of many potential public health and social problems. To say the least, the widespread use of these drugs and the publicity being given to their accomplishments is currently adding much confusion to an already highly confused situation. It might be useful, therefore, to examine some of the major problems that the availability of large amounts of the tranquilizing drugs poses to the psychiatric profession, other branches of medical practice, the epidemiologist, the social scientist, and the biostatistician. Public Health Problem of the Mental Disorders To understand the concern of public health workers with the widespread use of the tranquilizing drugs requires an understanding of the epidemiological approach to the study of disease as it affects population groups and the application of such knowledge to the control and/or prevention of disease. Gordon (6) states: There is a basic scheme by which the epidemiologic method is put to practical use in communicable and other mass disease. It involves, in order, a definition of the nature and the extent of the problem; a search for factors of causation of the disease and its distributions, through study in nature of affected populations; the formulation of principles for a program of control based on demonstrated cause and directed towards prevention of death, defect and disability; and finally, field or statistical evaluation of results derived from control measures. Thus, the epidemiologist is interested in understanding those factors that explain how a disease develops in a population and that govern the rate at which new cases develop. He is interested also in understanding those factors which determine whether the interval between onset and termination of a disease shall be long or short, whether a disease shall be acute or chronic, or, stated differently, in finding those factors which determine the rate at which disease is "arrested," "cured," or eliminated from the population by death or other means. Any therapeutic agent (drug, vaccine, antibiotic) which presents the possibility of being able either to prevent an illness per se or to prevent or ameliorate some of its disabling symptoms and consequences is of great public health significance, particularly when the diseases in question are responsible for as much disability and are as costly to society as the mental diseases. Clearly, the tranquilizing drugs have this potential. A point to be emphasized is that, for the therapeutic agent to be useful in attacking a public health problem on a large scale, it must first be ascertained that the drug is safe for the patient, that it does not produce more disability than it prevents, and that it does not affect adversely the expectation of life of the patients treated with it. As Pickering stated in his presidential address to the section of experimental medicine and therapeutics of the Royal Society of Medicine (7): Before concluding that the change for better or for worse in the patient is due to the specific treatment employed, we must ascertain whether the result can be repeated a significant number of times in similar patients, whether the result was merely due to the natural history of the disease or in other words to the lapse of time, or whether it was due to some other factor which was necessarily associated with the therapeutic measure in question. And if, as a result of these procedures, we learn that the therapeutic measure employed produces a significant, though not very pronounced, improvement, we would experiment with the method, altering dosage or other detail to see if it can be improved. In effect, there must be evidence from carefully designed experiments and clinical trials which permits a scientific assessment of the agent. It is also important that public health administrators interested in planning large-scale hospital and community programs to cope more effectively with the mental disorders should anticipate the various health, economic, and social problems that may result as a consequence of the use of these drugs. Action of the Tranquilizing Drugs The significant action of the tranquilizing drugs is their ability to reduce motor activity, disturbed behavior, tension, and anxiety without producing sleep. The tranquilizing effect has been reported to be of value in the treatment of psychotic patients by diminishing disturbed behavior without preventing patients from continuing to take part in psychotherapy and in occupational, recreational, and other forms of therapy. It is further claimed that these drugs make accessible to psychotherapy patients who otherwise might not have been accessible had these drugs not been available. Overholser (2, p. 182) summarizes a prevailing attitude toward the significance of the tranquilizing drugs in the following statement: The general consensus seems to be that the significant thing about chlorpromazine is that it makes the dis turbed patient calmer, although still clear, and he therefore becomes accessible to many forms of psychotherapy: group psychotherapy, individual psychotherapy, any of the things of a rehabilitative or curative nature that go on in a hospital. The literature contains many illustrations of the significant differences found in ward behavior of mental hospital patients following the introduction of the tranquilizing agents (1-3). Use of these drugs has resulted in a marked reduction in or elimination of not only motor excitement but the necessity for seclusion and restraint. There has also been a tendency on the part of medical staffs to reduce the use of electric convulsive therapy, insulin, and lobotomy. However, as Hoffman (8) points out in discussing the effects of reserpine: |