5. Oversimplification of psychiatric treatments in advertising with implications that tranquilizing drugs are sufficient by themselves Examples taken from advertising material for drug B. Additional reference: West, E. D., and da Fonseca, A. F., controlled trial of meprobamate, British Medical Journal, November 24, 1956, 1207. USE OF QUASI-SCIENTIFIC MANNER OF ADVERTISING Drug F: Advertisement in free medical journal given to physicians, but containing scientific articles. Advertising generally considered to be conforming to lower standards than in other medical journals. However, the major drug firms use these journals for their advertising. Why should they pursue two standards of advertising when these are permitted? This advertisement contained seven references: 1. In press. 2. Published, but article contained no controls and longest period of observation was 6 months although ad said drug could be used over long periods of time. 3. In press 4. Published and competent with controls but misrepresented in the advertisement. The author emphasized the point that the drug studied did not offer greater freedom from complications or recurrences than placeboes (blank pills), yet the advertisement implies that it does. 5. Personal communication to the drug manufacturer. In other words of the 7 references listed, 5 were inaccessible for practical purposes. Of the 2 which were accessible, 1 was an entirely inadequate study. The one careful study quoted and accessible was seriously misrepresented as saying something the author never said and in fact he had said the opposite. EXHIBIT 12 [Reprinted from JAMA October 12, 1957, pp. 657-661] "TWIXT THE CUP AND THE LIP Harry F. Dowling, M. D., Chicago The development of a drug is an intricate process, involving researchers, manufacturers, clinical investigators, and many others. All of the information obtained about the drug must be brought to the practicing physician, who is the one to prescribe or administer the drug, and it is important that this information be timely and accurate. In the evaluation of new drugs, the practicing physician should do three things. First, he should learn the mechanism by which the drug works, rather than the results somebody says it will produce. By learning the generic name, the physician can understand much about the drug. Second, when asked by a patient to prescribe a drug that is not indicated, the good physician explains rather than prescribes. Last, doctors should read pharmaceutical advertisements critically, and not be hesitant to write to editors of journals as well as drug manufacturers when they question the truth. Only in these ways can the medical profession advise and assist such a dedicated organization as the Food and Drug Administration to properly judge the merits of a drug. Drugs are discovered, manufactured, and tested by scientific methods. On the other hand they are produced and marketed through a blend of personal and social motives; they are prescribed by doctors with varying knowledges and skills, and they are taken by patients who have different degrees of information, interest, and precision. Drugs are brewed in the cup of science, they are drunk through a patient's lips, and "there's many a slip twixt the cup and the lip." Scientific attention is usually turned toward the discovery of drugs; in the present paper I shall consider the path from their development to their use. As an example, let us take chlortetracycline, one of the first antibiotics to be produced by a pharmaceutical company. After screening hundreds of specimens of soil, Duggar isolated Streptomyces aureofaciens, in the fall of 1945. Its in vitro antibacterial activity was demonstrated later in the same year. Preparation of crude concentrates that protected animals against bacterial infections required an entire year, and further purification and initiation of large-scale production required nearly 2 years more. It was not until September 1948 that clinical tests were considered adequate for submission of the data to the Food and Drug Administration. Approval by this agency was granted in October 1948, and chlortetracycline was finally marketed on December 1, 1948.1 The path of a drug from cup to lip, which took over 3 years in the case of chlortetracycline, is shown in figure 1. Basic research by medical schools, pharmaceutical companies, and others leads to the discovery of a new drug. It is produced in a form suitable for administration by the pharmaceutical manufacturer. Its efficacy must then be tested in vitro, and its efficacy and toxicity, in lower animals. If these tests are satisfactory, the drug is tried in patients by investigators outside of the pharmaceutical industry. The accumulated information is then submitted to the Food and Drug Administration for approval or to the National Institutes of Health in the case of biological products. When approval is forthcoming the drug can be packaged, advertised to the profession, and sold. At the same time, investigators who have tried the drug in patients are informing the medical profession when and how this drug should be used. All of these paths lead a single goal: administration to patients. This benefits the patient through the prevention, amelioration, or cure of disease and brings profits to the pharmaceutical industry and related groups. These twin benefits act as sources of energy to start the process over again. FIGURE 1.-Diagonal lines refer to the pharmaceutical industry; horizontal lines, to the investigators in medical schools and hospitals, and stippled areas to other groups (Government agencies, the practicing physician, and the patient). This system is an outstanding example of man's genius for organization. It has been developed by idealistic motivation, along with down-to-earth planning; it balances the interests of scientist, investor, producer, physician, and patient. And it has filled the cup to overflowing. The number of effective drugs is beyond the highest hopes of a century ago and is increasing all the time. In the 30-year period from 1905 to 1935 new drugs were introduced into the United 1 Hardy, S. M., Lederle Laboratories division, American Cyanamide Co.: Personal communication to the author. NOTE. From the Research and Educational Hospitals and the Department of Medicine, University of Illinois. Chairman's address, read before the section on experimental medicine and therapeutics at the 106th annual meeting of the American Medical Association, New York, June 4, 1957. 25489 0-58--15 States Pharmacopeia at a rate that averaged 6 per year, while in the succeeding 20 years the average yearly rate was 37.2 Yet the system, like all systems, can be perverted. The process of fundamental research, followed by the development of worthwhile new products and the successive stages necessary to bring them to the patient, is a long one. The desire to help the patient and the desire for profits provide sufficient energy to power the process; but some have discovered that if this energy is applied at a later stage, the path from profit back to profit again can be speeded up. This is shown in figure 2. Energy, instead of being directed toward research and the discovery of new drugs, is frittered away on dozens of unimportant modifications designed to compete with drugs that are already available. One example of this is the marketing of mixtures of antibiotics. As of November 1956, there were on the market 29 preparations containing 2 antibiotics, 20 containing 3, 8 containing 4, and 4 preparations that contained 5 antibiotics apiece. I have shown elsewhere that there is no good reason for the use of any of these 61 mixtures. 4 If this trend continues, we shall soon reach the chaos that exists in Germany. According to a recent article in The Lancet, there are about 6,000 proprietary preparations marketed in Western Germany, made by 565 different firms. Most of these preparations contain several or many substances; 5 or 6 is the rule, and more than 10 is not at all rare. One firm has put 22 different substances into 1 tablet. It has become unfashionable to use one drug by itself. When the author of the article asked for ephedrine tables in a big hospital, he was told that these were no longer stocked. This sidetracking of energy within the system has further effects. When the drugs that are produced so prodigally are tested in the laboratory, only those are eliminated that are obviously toxic. Drugs that are superfluous because they duplicate the action of others that are already available and drugs that are of dubious effectiveness are continued in the process and eventually reach the market (fig. 2). For instance, 33 different antihistiminic drugs are being sold at present, all having practically identical actions but different names and dosages. Similar excesses can be found among other groups of drugs, especially the vitamins, the antispasmodics, and the tranquilizing drugs. 6 At the next step in the process pressure is applied upon investigators to report that all the drugs recently produced are beneficial to patients, that they are better than existing drugs, and that they have fewer side effects. Since this tremendous multiplication of new drugs exhausts the existing facilities for clinical investigation, inexperienced investigators are cajoled into assessing drugs in patients. Some learn the proper methods and acquire a critical sense during the experience; most do not but unwittingly call a spade a diamord—to the confusion of the Food and Drug Administration, the exasperation of the experienced and honest investigators, the quick profit of that particular manufacturer, and the loss of prestige of the medical profession and of the pharmaceutical industry as a whole. Increased pressure is applied in turn upon the Food and Drug Administration. No words can speak too highly of the services rendered to physicians and patient alike by this dedicated body of public servants. Quietly and unobtrusively, patiently and honestly, they attempt to judge the merits of a drug solely on the evidence presented to them. Their problems, however, are similar to those of every regulatory agency of the Government: they hear one side of the story loudly and incessantly; they hear the other side only sporadically and feebly. It is the drug manufacturer's business to present his viewpoint; it is to his interest to present it attractively and forcibly. The consumers, on the other hand, have no paid advances. Their viewpoint is presented by persons who 2 Beal, G. D.. director of research, Mellon Institute for Industrial Research, and Griffiths, M. C., editorial assistant, Pharmacopeia of the United States of America: Personal communication to the author. 3 Welch, H., Director. Division of Antibiotics, Food and Drug Administration, U. S. Health, Education, and Welfare Department: Personal communication to the author. 4 Dowling, H. F.: Mixtures of Antibiotics, Journal of the American Medical Association 164: 44-48 (May 4) 1957. Medicine and the Drug Industry in Germany, from a correspondent, special articles, Lancet 2: 1304-1305 (December 22) 1956. Holland, A. H., Jr., Medical Director, Food and Drug Administration, U. S. Health, Education, and Welfare Department: Personal communication to the author. must spare time from everything else to do it and who are not usually well acquainted with these channels of communication. This is all the more reason why, in the field of the regulation of drugs, physicians and organizations of physicians, such as the American Medical Association, should make it their business to advise the Food and Drug Administration. The excess pressure is applied next to advertising. The description of the drug on the label and the circular accompanying the package must be accurate and well documented and must be approved by the Food and Drug Administration. Advertising pertaining to a drug, on the other hand, is under the jurisdiction of the Federal Trade Commission, who can stop a company from making a particular statement only if the statement constitutes an unfair or deceptive act. This opens the way for abuses. Within recent years the drug industry has discovered that the techniques that had been used so successfully in the advertising of soaps and toothpastes and of cigarettes, automobiles, and whisky could be used as successfully to advertise drugs to doctors. Advertising to doctors has become flamboyant, as shown by two-page gaily colored spreads in nearly every medical journal. Advertising has become incessant; nearly identical advertisements for a new drug appear in each day's mail for weeks on end. Advertising is without question confusing. The multiplicity of trade names makes it difficult to remember the actions and uses of any. Richardson Evans, writing in the English National Review in 1890, said: "Suppose a dozen people are in a small room. Two begin to talk to each other at the top of their voices. The others must either give up conversation or shout also. The result is that no one hears as well as before and that comfort is at an end. So it is with advertising *** "7 Advertising to doctors has now reached this peak, and we are deafened by the din. This leads us to the next step in the process: the use of drugs by the practicing physician. The doctor's sources of information include textbooks, journals, and speeches, written or delivered by those who have studied the drugs in laboratories and in patients. Most practicing physicians do not see a sufficient number of patients with any one disease to make a critical trial of a new drug themselves. When the drug becomes available the most they can do is to acquire skill in its use. If this information is beamed clear and true to the doctor, he is willing to listen to the commercials and patronize those who have, through their investments and their foresight, brought the drugs to him. But today the commercials are so loud, incessant, and brash that they jam the channels of communication. The bewildered physician prescribes by suggestion and not from information. At this point the reader will say: "Well, even if this makes the physician a shifting weathervane and the patient an unwitting guinea pig, the writer must be an ingenuous idealist to expect the pharmaceutical manufacturers to change their methods so long as they are putting money in their pockets." This last phrase is the key to the answer. You will recall that the twin sources of energy for the system are profits and benefit to the patient. It is already evident to most doctors, and it will soon become evident to the public, that energy has been diverted from the pathway that leads to the greatest benefit to patients. With the inevitable disillusionment that comes with the failure of each useless modification to make any advance, the pharmaceutical industry will lose its prestige and with this will lose its financial backing. It will fall, and the medical profession will be dragged down with it. Since such a catastrophe would involve doctor, industry, and patient alike, we may well look to see what each can do about it. 7 Turner, E. S.: The Shocking History of Advertising. New York, E. P. Dutton & Co., Inc., 1953, p. 169. To physicans I would say first: Keep informed. Learn the mechanisms by which drugs work, rather than the results somebody says they produce. Look for and remember the generic name, for this tells something about the drug, while the trade name tells nothing. Avoid substituting drugs for diagnoses. Furthermore, since advertisements for new drugs appear so quickly, some mechanism must be set up to bring authoritative information rapidly from investigator to practicing physician. The challenge is thrown to medical societies, medical schools, and specialty groups; keep the profession informed. My second suggestion to physicians is, inform the public. As Vannevar Bush has said: 8"***public opinion is not formed by the radio and the press or even by those who control these mediums. It is formed by that minute fraction of the population which thinks and speaks, by that small but powerful minority, disagreeing on every issue, arguing and ridiculing, which looks beyond the diversion of the moment and influences because it labors to understand." With regard to drugs we are that "small but powerful minority," and we must use every means to make our opinion known. When a doctor prescribes a drug for no reason except that the patients want that drug, the doctor is allowing the lay press to take over the job of health educator to his patients. The good physician explains instead of prescribing. My third suggestion to doctors is to reject misleading information and repudiate those who purvey it. Doctors should read advertisements critically. They should write to editors of journals and to drug manufacturers when they question the truth of an advertisement. They should not listen again to someone who has misled them once. They should prescribe as far as possible only those drugs made by companies with high standards of advertising and read only the journals that accept that kind of advertising. In the past the council on pharmacy and chemistry of the American Medical Association (now the council on drugs) has led the fight against false advertising by quacks and vendors of patent medicines. The battle front of today has shifted, and false advertising to the public is no longer the major issue. For the future the council needs to aline its forces against false advertising to the doctor. To pharmaceutical manufacturers, I would make three suggestions: (1) That they emphasize basic research and the discovery of new drugs and avoid minor variations of existing drugs; (2) that they weigh the proposals of their sales 8 Bush, V.: Professional Collaboration, Science, 125: 49-54 (January 11) 1957. |