with few exceptions, I know them to be men of good will, whose interest extends beyond the purely financial to a strong desire to be of service not only to the medical profession but to mankind in general. Unless we bring to the attention of this ethical and well-intentioned group the rare exceptions, it will be impossible for the necessary moral suasion to be exerted, and they, too, may find themselves debased by attempting to meet competition. The negative criticisms which I have had to offer are few compared with the multiple benefits, but I believe action must be taken promptly and effectively in order to maintain that which is begun so promisingly. EXHIBIT No. 5 [Reprinted from JAMA March 1, 1958, pp. 1040-1041] REPORT OF THE COUNCIL ON DRUGS [The council has authorized publication of the following report. Nonproprietary terminology is used for all drugs that are mentioned; when such terminology is not considered to be generally well known, its initial appearance is supplemented by parenthetic insertion of names known to be applied to commercial preparations.-H. D. Kautz, M. D., Secretary.] PSYCHOTHERAPEUTIC DRUGS The introduction of a multiplicity of psychotherapeutic drugs and of new terms, such as tranquilizer, ataraxic, normalizer, calmative, neurosedative, psychic energizer, pacific, anticonfusion, and antihallucinatory, creates a difficult situation for the average physician. He is confronted with the problem of evaluating claims of usefulness for a wide variety of chemical substances with diverse pharmacological effects, which are proposed for the treatment of neurotic and psychic disorders. The terms "tranquilization" or "ataraxia" in referring to the human mental state have been variously defined, but for simplicity they can be considered to be more or less synonymous with peace of mind. As such, they are obviously psychological rather than pharmacological terms, since the state can be produced by a multitude of drugs which either depress or stimulate the central nervous system and by others which exert only a peripheral effect on organ structures. Thus, a tranquil state can be accomplished by nonspecific sedation (alcohol, barbiturates), by analgesics (acetylsalicylic acid, morphine), by skeletal muscle relaxants (mephenesin, meprobamate), by autonomic suppressants (chlorpromazine, reserpine), and by many others. Peace of mind can also be created in depressed individuals by the judicious use of substances that are pharmacological stimulants, such as amphetamine. In the broadest sense, therefore, the reversal of any clinical disorder, even by drugs with only peripheral effects (epinephrine in asthma and digitalis in cardiac decompensation), can result in peace of mind by relieving anxiety. This concept is the fundamental basis of psychosomatic medicine. From a practical point of view the time has long since passed when it would be useful, or even possible, to attempt to establish the designation tranquilizer or even specific tranquilizer as a pharmacological term that could be considered synonymous with what might be termed "autonomic suppression." Likewise, it is no longer feasible to limit the application of such a term to particular substances, such as chlorpromazine and reserpine, whose introduction into psychotherapeutic practice, because of unique pharmacological properties, created the present dilemma. Indeed, it appears probable that the gradually increasing number of new drugs, as well as new terms, will add to rather than detract from the confusion in this important field. It seems wise to bear in mind that regardless of terminology, the ideal objective of psychotherapy with drugs is to induce an improved mental state, irrespective of what subjective symptom or objective sign is being treated. This should be done with agents that produce no undesirable subjective responses, are lacking in toxic side actions, and exert no summative effects with other drugs unless the latter are beneficial. In accordance with the foregoing considerations, the council has voted to abandon the section on ataraxics in New and Nonofficial Drugs and to describe agents proposed for use for their particular effects on the central nervous system, in accordance with their fundamental pharmacological classification, insofar as this is known. On the basis of present knowledge, the drugs in this general category can be classified under the following headings: I. Antihistamines A. Psychotherapeutic antihistamines a. Hydroxyzine (Atarax) hydrochloride II. Central Nervous System Depressants 1. Analgesics 2. General anesthetics 3. Hypnotics and sedatives B. Selective Depressants 1. Anticonvulsants 2. Antihistamines (as above) 3. Antitussives 4. Central muscle relaxants (skeletal muscle relaxants), sedative non (a) Mephenesin (Avosyl, Dioloxol, Kinavosyl, Lissephen, (b) Mephenesin carbamate (Tolseram) 5. Central muscle relaxants (skeletal muscle relaxants), sedative (a) Meprobamate (Equanil, Miltown) (b) Phenaglycodol (Ultran) (c) Promoxolane (Dimethylane) 6. Central parasympathetic suppressants (a) Benactyzine (Suavitil) hydrochloride 7. Central sympathetic suppressants, phenothiazine derivatives (a) Chlorpromazine (Thorazine) hydrochloride (b) Mepazine (Pacatal) hydrochloride (c) Perphenazine (Trilafon) hydrochloride (d) Prochlorperazine (Compazine) maleate (e) Promazine (Sparine) hydrochloride (f) Triflupromazine (Vesprin) hydrochloride 8. Central sympathetic suppressants, rauwolfia derivatives (b) Deserpidine (Harmonyl) (c) Rauwolfia (Raudixin, Rauserpa) (d) Rescinnamine (Moderil) (e) Reserpine (Rauloydin, Raurine, Reserpine, Reserpoid, Roxinoid, Sandril, Serpasil, Serpiloid ) III. Central Nervous System Stimulants IV. Miscellaneous Agents (a) Methylphenidate (Ritalin) hydrochloride (a) Azacyclonol (Frenquel) hydrochloride EXHIBIT 6 [Reprinted from New England Journal of Medicine, December 5, 1957, pp. 1117–1120] EDITORIAL RESPONSIBILITY FOR MEDICAL ADVERTISEMENTS By Joseph Garland, M. D.2 BOSTON 1 Despite the distances that separate us and the varying points of view that we may occasionally entertain, it is obvious that a number of problems are common to all. Not the least of these is our editorial responsibility for the character and quality of the advertisements that our journals accept and that 1 Presented at the 3d Congress of the Union Internationale de la Presse Médicale, London, September 14, 1957. 2 Editor, New England Journal of Medicine. are so vital to their prosperity. This problem has given rise to a growing concern because of the tremendous expansion of the pharmaceutical industry in recent years and its resulting pressures, and because of an increasingly uncomfortable awareness of our own ethical obligations in the matter. This impressive growth is the logical outcome of a succession of pharmacologic events. Within 35 years-scarcely more than a generation--the pharmacopoeia has undergone some of its most revolutionary changes, substituting for many time-honored remedies of questionable value such specific additions as insulin ; liver and its extracts; the sulfonamides; the antibiotics; various hormones; the antiemetics; certain hypertensive and hypotensive agents, and a galaxy of drugs that lower or elevate the mood-those panaceas that pacify the universal feeling of outraged frustration or incite its victims to continued rebellion. And new agents are continually streaming over the pharmaceutical horizon, including certain exciting solvents that remove cholesterol from the blood stream as carbon tetrachloride removes a grease spot. Almost equally impressive are the combinations of vitamins in all their multiplicity, lined up like task forces, each component ready to carry out its specific assignment, supplying in capsular concentration and at considerable cost that which nature has otherwise so lavishly provided. And we are told that there is much more to come, when the pharmacologists really get down to business. Practically the entire pharmaceutical industry, in the course of this phenomenal growth, has become hugely prosperous, or so it seems to us, and the influence that has accompanied this prosperity concerns the progress of medicine in a number of ways. On the positive side it has been directed into a variety of useful channels, especially along the lines of postgraduate education, scientific research, and financial aid to many worthy projects, including the establishment and support of independently operated scientific and philanthropic foundations. On the other hand, there are indications that this growing influence, if exerted indiscriminately, may have an increasingly undesirable effect on medical progress and practice. This will certainly happen unless some restraint more adequate than now exists is placed on it by those who direct its policies, working with a more intelligent understanding of the needs of the medical profession and, indeed, of humanity at large. This untoward effect is seen in the recommendation, through the various advertising mediums, of pharmaceutical products in cases where they are not specifically indicated; in the encouragement of unnecessary or even undesirable combinations of agents, and in their exploitation beyond the limits of their usefulness. It is seen in the proffering to and the acceptance by the profession of gratuitous patronage outside the scope of reasonably friendly professional relations. The physician is in danger of surrendering some of his responsibility for the enlightened care of his patients-as well as some of his prestige-in favor of becoming to too great an extent a purveyor of proprietary remedies about which he may sometimes lack sufficient knowledge for their consistently intelligent employment. A release in February 1957, from Paul de Haen, of New York, a consultant to the pharmaceutical and allied industries, indicates that the competition inside the drug business is indeed keen. According to this analysis of the American market 126 drug firms-the trade journal Printer's Ink* places the total number of manufacturers at 250-introduced 401 new products in 1956, compared with about the same number launched by only 80 firms in 1948. It is encouraging for those who have maintained a belief in the desirability of single therapeutic agents who prefer scientifically directed and reasonably accurate therapy to peppering a disease with birdshot-that more single chemical entities were put on the market in 1956 than in either of the previous 2 years. There were nevertheless, only 42 of these solitary agents introduced, compared with 280 compounded products. The difference between these figures and the total 401 was made up by 79 duplicates of products put out by other firms. These fresh offerings consisted of various tranquilizers, hormones, diuretics, laxatives, antibiotics, blood-pressure reducers, muscle relaxants, combinations of vitamins, blood builders, urinary antiseptics, antihistamines, and bioflavonoids. Such competition is responsible for both the advertising offensive and the offensive advertising; and yet it could be turned to account in the reformation of the 3 Editorial. Pills and potions, New England Journal of Medicine, 256: 859, 1957. Day, C. Ethical-ad trends for 1957. Printer's Inc. 259: 21-23 and 77, 1957. business if the doctor insisted that his good will was dependent on ethical marketing practices and the ultimate welfare of the patient as the only objective. There is, happily, a growing concern, which is affecting even our nonmedical press, over the character of some of the drugs being promoted and the manner of their promotion. This concern is largely a result of the methods by which modern publicity is attained-especially as it affects the sale of such doubleedged tools as today's pharmaceutical products. It is a publicity that includes the glowing encomiums, the bold suggestions regarding the value of the wares that are offered, and in general the insistent persuasiveness from which modern advertising techniques seem to have become inseparable. One need not ask what meat our Caesar eats. As the pharmaceutical industry has become bigger business it has inevitably been drawn into an acceptance-perhaps not always willingly-of these promotional methods of big business, often in violation of that unique phenomenon known as good taste. Such methods carry with them a risk that the legitimate and erstwhile mutually respected partnership between pharmacy and medicine may turn into one in which medicine becomes a junior partner only to the big business of pharmaceutical manufacturing, with its large-scale exploitation of potent and consequently dangerous drugs. For agents that have a dynamic effect on physiologic functions may alter those functions adversely as well as favorably, and their availability carries with it an added responsibility for their use. We are all familiar with the three chief methods of publicizing pharmaceutical products: the visit from the personal representative, or detail man; advertising to the physician by direct mail; and that which concerns us most at this momentadvertising in our medical journals, of which there are now some 6,000 in circulation. The relative use of these methods was brought out in a survey of 23 commercial organizations made by Modern Medicine last winter, which demonstrated that 54 percent of their promotional budgets was spent on the detail men, 13 percent on direct mail, and 12 percent on the journals. The remainder was allocated to drug-trade publications, house organs, samples, literature, conventions, television programs, cocktail parties, and so forth. So far as the value of these three main methods is concerned, that of detailing seems to be generally acknowledged, whereas direct mail, to the number of 3,000 or 4,000 pieces per year per doctor, is said to have passed its peak-happily for both postman and physician. Journal advertising, despite its relatively low place in the budget, is the most substantial of the three methods, for it is the one that achieves a permanent place in the record of medical progress, and it is the only one directly sanctioned by the profession-the one for which we have an obvious responsibility. In regard to the discharging of this responsibility, the Modern Medicine symposium just referred to indicates that advertising in medical journals can be improved in various ways. Thus, the doctor desires and should be given more specific information regarding the products advertised, and their proper use; he desires and should be given authoritative references when clinical claims are made, and he desires and should be given a presentation without superfluous and distracting verbiage, although he, too, like his less dedicated fellows, reacts favorably to an attractive advertising layout. And there is no gainsaying the effectiveness of stimulating displays, and their propriety, so long as the text contains the truth, the whole truth, and very little else. For the physician cannot surrender to the manufacturing chemists or their advertising agents any part of his responsibility in the treatment of his patient nor should they want him to. It is to their interest as well as to his to put at his service accurate information about the total effects, both beneficial and harmful, of any advertised drug or combinations of drugs, with their dosages, and he should be supplied with reliable and authoritative references to the studies that have been responsible for their acceptance. The importance of this final factor cannot be overemphasized, for it is likely to be the only reliable scientific evidence of the value of a new product. To see that he is thus served should be at least in part the business of the editor, who is directly concerned with the character of the advertisements that his journal carries, as well as with the indoctrination of his readers by means of its scientific and editorial text. Different editors, obviously, have varying degrees of responsibility in respect to the actual selection of the advertising material accepted and the manner of its presentation, depending on their relations with the publishers. This responsibility may range from a total insulation from the business policies of the periodical, to the total administration of all its affairs-scientific, literary, and financial. In the first instance, whether the journal is owned and operated by a publisher for profit or by a society or association as a means of communication with its members and others, the editor is charged only with the oversight of its scientific and editorial content. It is hard to conceive, however, of an editor indifferent to the character of the advertisements carried by the journal for which he is otherwise responsible, and it may be hoped that any editor's readers would expect him to exert, by one means or another, at least some influence on the type of advertising matter that would be permitted to appear. In the second instance one may envision the other extreme of responsibility, in which the editor is put in full charge of the publication, often society-owned, and is accountable to whoever employs him for the quality of the original articles, the pitch of the editorial tone, the character of the material accepted for advertising, the stability of the financial arrangements and the punctuation of the text, if any. To him goes the blame for the mistakes that he did not anticipate and prevent, as well as the credit for the successes that he did not personally achieve. The selection of advertising material-the drawing of the line that separates the acceptable from the unacceptable-may reasonable vary with the type of the journal and its readers and the philosophy that may be observed in this respect. What, after all, are an editor's obligations to his readers, to the public and to the advertisers themselves, one of whose duties is to make a reasonable profit, whatever that may be? To what extent shall the physician who reads the advertisements be protected against his own enthusiasm if he chooses to take too literally all the suggestions that reach him in such glowing terms, and to prescribe indiscriminately drugs the action of which he does not understand, and the ill effects of which may have been insufficiently emphasized? To what extent shall the public be protected against the manufacturer who has invested several million dollars in the production and marketing of a tranquilizer, and against the physician who is too easily persuaded to help him in this benevolent project? To what extent must the editor be concerned over the fact that the financial solvency of his journal depends on the goodwill of the advertiser, and to what degree is he protected by the valuation that the manufacturer places on the goodwill of his particular journal? These are questions difficult to answer, and few editors, I presume, would be bold enough to set themselves up as sole arbiters of the acceptability of advertising material. If the final responsibility is theirs they must protect themselves by stated principles and policies and expert advice. The New England Journal of Medicine, the forebears of which had succeeded in surviving a long and independent career under the private but nonprofit ownership of successive small groups of local physicians, had to reappraise its methods of operation when it became the property of the Massachusetts Medical Society in 1921. The society maintains a general oversight of the journal through its representative council, but delegates the actual publication to a committee, which in turn appoints an editor from the membership of the society and assigns to him the responsibility for all the details of the operation. The chain of responsibility is thus reasonably clearly defined, the working staff being accountable to the editor, the editor to the committee and the committee to the council. The matter of the procurement of advertising is an old problem, solved to a considerable degree, after the journal's purchase by the society, through the services of what was then the cooperative advertising bureau of the American Medical Association. This bureau, established to solicit advertisements for the journals of the various State societies, has regularly obtained the greater part of the national advertising contracts for the 35 or so periodicals that have subscribed to its offices. The New England Journal of Medicine, having achieved by 1954 a widely distributed circulation in considerable excess of the membership of the State society, regretfully relinquished its association with the bureau in order to frame on a broader scale its own policies in respect to advertisements, and to follow its own procedures in this regard. It has adhered in general to the principles established by the council on pharmacy and chemistry of the American Medical Association but with somewhat more liberal interpretations. The most important of these principles are that advertisements shall not be accepted "which, either by intent or inference, would result in deceiving, defrauding, or misleading the reader; that sweeping superlatives, extravagant statements and unfair comparisons are to be avoided, and that claims for superi25489-58-13 |