e patients he is studying. Obviously, the less ffective the new agent, the greater the need for roper controls, to forestall erroneous conclusions. Advocates of the historical-control approach to rug evaluation argue that in many instances their ndings are subsequently borne out by controlled udies. This argument is specious. For every drug valuated by the historical-control method whose ficacy is later confirmed by controlled procedures, ere are half a dozen others which never make e grade. In the present experiment the failure the controlled energizer study to confirm the controlled study based on the same patients, ith the same observers, is a striking case in point. he argument that inefficacious agents will evenally fall by the wayside is also a poor one. How any patients and physicians will have been deded in the meantime? How much money wasted? ow much research inhibited or misdirected in e belief that a good treatment is already availle? 4 The "double-blind" technique does not necesrily require the use of a placebo. For example, e of the recent Veterans Administration Coopative Studies of Chemotherapy in Psychiatry is established that chlorpromazine, at a certain sage level, is unquestionably superior to a place> in the alleviation of certain symptoms in hostalized schizophrenics. Consequently, chlorproazine rather than a placebo might be used as e standard of comparison in future studies of wer tranquilizers. However, the results of this articular VA study could not be used as an arguent for abandoning the use of the placebo in anquilizer studies involving nonschizophrenics, itpatients, or substantially different dosage levels chlorpromazine. It should be emphasized that the "double-blind" a necessary but not a sufficient condition for drug study to be scientifically defensible. Rently a segment of the pharmaceutical industry s recognized the apparent value of the claim at a drug was tested under "double-blind" contions, and promotional material has been prered under the caption of "Double-Blind Studies." is is hardly adequate testimony that a study has erit. The need for other essential requirements, cluding randomization, operationally defined sessment instruments, and appropriate statistical alysis, has recently been discussed in detail sewhere.". It should also be noted that in a well-designed periment it is difficult to conceive of a situation which the results might be of practical or cliniI significance and not be of statistical significance. wever, statistical significance is no guarantee clinical significance. A statistical confidence level merely a probability statement about the reprocibility of the results. Whether the magnitude a drug's efficacy is sufficient to warrant its con tinued use is a clinical or management decision, not a statistical one. Such a decision obviously will be a function of the availability of other treatments, the cost of the medication, and its toxicity. The decision can be facilitated if the assessment instruments are so calibrated that differences obtained with them can be translated into language that is meaningful to the clinician and to manage ment. Summary Less than 10% of published reports on tranquilizer and antidepressant drugs meet minimum standards of scientific acceptibility. The purpose of the present experiment was to determine whether this practice has any practical significance. Both drugs used in the study were actually placebos. When an uncontrolled and impressionistic method was used to evaluate the 2 new "drugs," 53% to 80% of the patients were said to have benefited from them for an average of 2.6 to 4.9 of the 6 weeks they were taking them. An objective approach to evaluating the 2 "drugs" was also employed. This involved the use of matched control groups and objective rating procedures. According to this method of evaluation significant but temporary improvement was caused by the tranquilizer but not by the energizer "drug." The tendency to ascribe improvement to what were considered to be active drugs, and the discrepancy in one experiment between the controlled and the uncontrolled methods of evaluation, dramatically illustrates the dubious value of studies which do not employ double-blind and other controlled procedures in evaluating new psychopharmacological agents. 21 Bloomingdale Rd., White Plains, N.Y. (Dr. Loranger). This investigation was supported by a research grant from the National Institute of Mental Health, Public Health Service. References 1. Heilizer, F.: Critical Review of Some Published Experiments with Chlorpromazine in Schizophrenic, Neurotic, and Normal Humans, J Chron Dis 11:102-148 (Feb.) 1960. 2. Casey, J. F.; Lasky, J. J.; Klett, C. J.; and Hollister, L. E. Treatment of Schizophrenic Reactions with Phenothiazine Derivatives: Comparative Study of Chlorpromazine, Triflupromazine, Mepazine, Prochlorperazine, Perphenazine, and Phenobarbital, Amer J Psychiat 117:97-105 (Aug.) 1960. 3. Lindquist, E. F.: Design and Analysis of Experiments in Psychology and Education, Boston: Houghton Mifflin Company, 1953, pp. 266-273; 317-339. 4. Casey, J. F., and associates: Drug Therapy in Schizophrenia, Arch Gen Psychiat 2:210-220 (Feb.) 1960. 5. Modell, W., and Houde, R. W.: Factors Influencing Clinical Evaluation of Drugs: With Special Reference to Double-Blind Technique, JAMA 167:2190-2199 (Aug. 30) 1958. 6. Nash, H.: Design and Conduct of Experiments on Psychological Effects of Drugs, J Nero Ment Dis 128:129147 (Feb.) 1959. 73753 0-61-pt. 2——35 PREPARED STATEMENTS STATEMENT OF THE AMERICAN MEDICAL ASSOCIATION Re: S.1552, 87th Congress Drug Industry Antitrust Act Before Committee on the Judiciary By Hugh H. Hussey, Jr., M. D. July 5, 1961 Mr. Chairman and Members of the Committee: I am Dr. Hugh H. Hussey, Jr., of Washington, D. C. I am appearing here today as the Chairman of the Board of Trustees of the American Medical Association. I am also the Dean of the School of Medicine of Georgetown University. With me are Dr. Milford Rouse, Vice-Speaker of the House of Delegates, and Dr. Ernest B. Howard, Assistant Executive Vice President of the American Medical Association. The American Medical Association, as the national association of the physicians of the United States, has a serious and long-standing interest in drugs and any legislation concerning them. We have not, however, taken any position on S. 1552, as a whole, inasmuch as certain of the proposals in the bill, such as the Sherman Act and patent law amendments, are outside our area of competence. We will direct our remarks primarily to several of the provisions in Section 4, dealing with proposed amendments to the Federal Food, Drug and Cosmetic Act. These proposals will, in our opinion, directly affect the practice of medicine and the public health and are therefore within the area of knowledge of physicians and the A. M. A. Inasmuch as Section 4 of the bill proposes extensive amendments to the Federal food and drug laws, I would like to review briefly the history of the position of the American Medical Association with respect to this type of legislation. As early as 1891, the A. M. A. went on record as supporting the first proposals for a Federal food and drug law. It was not until 1905, however, coincident with the establishment of our Council on Pharmacy and Chemistry, later to become the Council on Drugs, that the Association threw its full weight into the struggle for a Federal pure food and drug law. The statute was enacted in 1906 following intensive legislative efforts by the A. M. A. Through the years the A. M. A. has closely followed the implementation and effectiveness of the 1906 Act. As early as 1911 the Association urged Congress to amend the Act so as to prevent false statements being made as to the results to be obtained from the use of medicinal agents. In 1933 the A. M. A., realizing that the existing Act had certain deficiencies, urged "the formulation and enactment of effective national food and drug legislation adequate for the protection of the people." Activities of the Association were instrumental in the passage of the present Federal Food, Drug and Cosmetic Act in 1938. In 1951, we supported the Durham-Humphrey Amendment, which is the law controlling the dispensing of prescription drugs. In 1953, the A. M. A. supported a bill, which was enacted as Public Law 217, 83rd Congress, authorizing the Food and Drug Administration to inspect pharmaceutical manufacturing establishments without first obtaining the permission of the proprietors. Only last year, the A. M. A. was one of the chief sponsors and supporters of the Hazardous Substances Labeling Act, which was enacted by the Congress as P. L. 86-613 and is now administered by the Food and Drug Administration. The A. M. A. is justly proud of its long history of support and sponsorship of legislation so directly connected with the public health and well-being. It should also be noted that Medicine has not limited its interest in food and drug matters to legislation. We have supplemented our legislative activities with a close and continuing relationship with the Food and Drug Administration. Our Council on Drugs, over the years, has had a number of members from the FDA, and numerous other Government physicians and pharmacologists have served as consultants to the Council in its drug evaluation program. Our Department of Investigation has enjoyed a long-standing close relationship with FDA in developing information on quackery and medicines and devices of questionable value. At the present time, the A. M. A. and the FDA are formulating final plans to act as co-sponsors of a National Congress on Medical Quackery, to be held in Washington D. C., on October 6-7 of this year, Our Committee on Cosmetics and the former Committee on Toxicology have also worked closely with FDA over the years, most recently concerning the above-mentioned Hazardous Substances Labeling Act. The Council on Foods and Nutrition is most active in exchanging information with FDA and in cooperating with it, the Federal Trade Commission, and the United States Post Office in sponsoring an aggressive program against food faddism and food and vitamin quackery. With this record of A. M. A. support and cooperation in food and drug matters as background information, I would like to comment on those sections of S.1552 which concern us directly as physicians and which will directly affect the practice of medicine and the public health. Section 4, Part (7) of the bill provides that a drug manufacturer must include with any drug information transmitted to physicians (A) a copy of all printed matter, which the Secretary of HEW has required to be included in any package in which the drug is distributed, and (B) in the case of a new drug, a complete statement of all findings of fact made by the Secretary with respect to that drug. The manufacturer must include in all advertisements and other printed matter issued, including those in medical journals, (A) the official name in addition to the brand name, (B) warnings, prefaced with the approval of the Secretary, as to any dangerous or harmful property of the drug, and (C) a full and correct statement of the drug's efficacy. Section 4, Part (13) proposes among other things that a new section 510 be added to the Federal Food, Drug and Cosmetic Act, which section would direct the Secretary of HEW to compile, publish and distribute to physicians, annually and at such other times as he deems necessary or desirable, a list of drugs which have the potentiality of serious, dangerous or harmful effects, and would also require the Secretary to publish and distribute to physicians and others copies of all printed matter which he has required to be included in any package in which any drug is distributed or sold. Before commenting on these proposals, let me cite the aims we, as phy sicians, are desirous of achieving. --We want all physicians to be well-trained and fully informed on all aspects of the practice of medicine. --We want this body of knowledge and reservoir of skills to include a high degree of competency in the selection and proper use of drugs. --We want a continuing and expanding flow of useful drug products placed at the disposal of these physicians. These are some of the aims we seek and which we have diligently pursued or more than a century. And since the American people now enjoy the finest |