EXHIBIT 46 TASHMOO FARM, Senator ESTES KEFAUVER, Vineyard Haven, Mass., September 2, 1961. Chairman, Subcommittee on Antitrust and Monopoly, DEAR SENATOR KEFAUVER: If you have lived on a farm you may understand the delay in not meeting Senator Hruska's request that I provide specific evi dence supporting the statement that much of the $750 million annual expendi ture of the drug industry in advertising and promotion, including the advertising so intellectually insulting to physicians on which their medical journals are financially dependent, "is for psychological gimmicks and misleading, or at times, even false statements." When one has but 6 weeks to meet the innumerable demands of wear and tear and unpredictable mishaps to flora, fauna, and machinery with which you have such an intimate and dependent relationship, important matters beyond the intimate domain take second place. Moreover, the question of how detailed the reply should be or indeed its importance was a deterrent to quick answer, for as I commented in response to Senator Hruska's request, "the nature of the promotional material was so generally recognized that I had supposed no specific validation in my testimony was required," other than the evidence referred to in my testimony; namely "editorials, committee reports, and comments by individuals in such professional journals as the New England Journal of Medicine, Pediatrics, the Journal of Medical Education, and the Medical Letter." I also assumed that much of such evidence was in the record, as your statement opening the legislation hearings on S. 1552, July 5, 1961, contains the following: Page 2. "The subcommittee has received numerous complaints from physicians, supported by abundant testimony in the record; to the effect that advertising and selling costs are excessive, wasteful, and often misleading." Page 11. "But above and beyond the quantity of this advertising and promotional material, there is the further and more serious question of its quality. It is indeed a serious question because if the physician is misled, the public health is endangered. It is, therefore, most dismaying to learn from medical authori ties that this advertising is often misleading and sometimes downright false." An additional deterrent was the belief that much of the specific evidence I might submit would duplicate what was already in the record or what, for example, was provided in the testimony of such as Dr. Charles May. I hesitated to add redundance to the hearings already burdened with Senators Hruska's and Dirksen's questions and comments that are so frequently farfetched or irrelevant as to suggest the purpose of confounding rather than contributing to an objective consideration of problems that so seriously concern our health and happiness: for example, Senator Hruska's statement that Government establishing standards that must be met to obtain payment from public funds for expenses incurred in providing services under a legislative program would lead to converting our democracy to a monarchy. Then there is his farfetched criticism of my quote from Dr. Hussey's testimony that occupied more time and will take more space in the Congressional Record than can be justified by any contribution relevant to the problem under consideration. A final deterrent, as commented to you, was the limitation on what could be done by September 1 because of my being on vacation on Martha's Vineyard and others being away on vacation during August. So what follows is merely what is available to me here with very limited access to files or assistance of others and without benefit of libraries. The articles by John Lear in the Saturday Review of Literature, September 5, 1959, on Roerig's promotion of Enarax and July 2, 1960, on Pfizer's promotion of Signemycin must be well known and available to the committee and hence need only to be referred to here. Then there is the evidence in I. T. Stone's Weekly, July 17, 1961, concerning the promotion that launched Pfizer's Diabinese which stressed "almost complete absence of unfavorable side effects." Your committee apparently has data on this as Stone comments "the Kefauver committee turned up a memorandum June 8, 1958, from the physician in charge of the testing program for Diabinese before it was marketed in which the president of Pfizer, John E. McKeen, was informed, 'In the evaluation of Diabinese we have encountered an incidence of toxicity which, at the least, is not less than seen with Orinase. We have encountered six cases of jaundice. The jaundice in each instance developed after 3 to 4 weeks of chronic daily treatment with Diabinese.' Today Pfizer adver tisements contain the at least misleading, and in the opinion of many physi cians, the false statement "Diabinese, the oral antidiabetic most likely to succeed." Upjohn's ad for Orinase (New England Journal of Medicine, Nov. 24, 1960) states that "an exclusive methyl 'governor' prevents hypoglycemia." Yet New and Non-Official Drugs has warned (1958 ed., p. 490): "The most serious of these (i.e., reported side effects) has been hypoglycemia, which is most likely to occur during the transition period." In the promotion of Decadon (Dexamethasone, Merck, Sharp & Dohme) the inadequately substantiated statement is made that “sodium retention, potas sium depletion, peptic ulcer, purpura, moonfacies, and hirsutism have occurred less frequently than with other corticoids." No mention is made of the unde sirable weight gain or nervous system stimulation that may occur. An ad (GP, July 1961) for Neopan cream (U.S. Vitamin and Pharmaceutical Corp.) states that this product is "virtually free from sensitization or irrita tion." Yet in chapter 19 of Neomycin (1958 ed.), Williams and Wilkins, entitled "Topical Use of Neomycin," Drs. Livingood and Shapiro state: "Evidence seems to indicate that the percentage of sensitization reactions to neomycin is increasing, or at least more physicians are recognizing such reartions" (p. 229), and "It is known that cutaneous moniliasis may develop at the site of application of other broad spectrum antibiotics, but there is some reasca to believe that this complication of therapy is more likely to occur after los application of neomycin" (p. 227). And in "Pyodermas and Their Management" (Medical Clinics of North Amer ica, May 1959) Drs. Nelson and McCarthy warn that "Recently, however, nec mycin has been found to cause a peculiar type of local contact sensitivity which usually manifests itself as an exaggeration of a preexisting dermatitis." Lederle's promotion of Lysine containing Incremin Drops purely on the bas of the questionably valid and unsubstantiated work of Albanese, before the criticism that supplements of lysine might be harmful as well as not beneficia had been appraised, is an example of the haste with which a possibly prof able promotion is undertaken. Pushing a product beyond reason or need is illustrated by Upjohn's prome tion of B, as the "Happy-baby vitamin" for "the wakeful baby who turns father into a floorwalker may simply lack B.." So doctors are persuaded to tell parents to buy excessively expensive Zymabasic Drops providing daty 5,000 I.C. of vitamin A (the need of such supplementation being a small fra tion of that amount, if any), 1,000 I.U. vitamin D (the need being 400), am 1 mg. Be (the need being no more than 0.3 mg.). Another example of exas gerated promotion is Johnson & Johnson's promotion of Liquiprin as "Safe: than aspirin" before substantiation of this claim by clinical testing and e tinuation of the claim without clinical validation. Wallace Laboratories in advertising Miltown (meprobamate)—says a "simple dosage schedule relieves anxiety dependably" and has "no cumulative effects in long-term therapy." Clinical experience certainly does not confirm the de pendably" and in the dosage recommended, particularly for their Deprol product where recommended dose is as much as three tablets containing 400 mg. ef meprobamate each four times a day, there is the danger of serious convulsion if therapy is discontinued abruptly. Time magazine of February 27, 1956, contains an interesting note on “M3 town" with a heading "Don't-Give-a-Damn Pills" and picture of "Miltown" Berle with legend, "It's worked wonders for me," that illustrates the gimmicks used in promotion. Household magazine, September 1956, contains a promotional article T¥ New Hormone That Calls a Halt to Heartbreak." Here one reads that new drug, Releasin, on the evidence of hospital trials, can save as many as i out of 10 of these (i.e., premature stillborn) babies. It can halt premature labor entirely in a great many cases, allowing the unborn infant to remain the full 9 months in the uterus ***. You will be reading and hearing mo about it-about its possible uses not only in premature labor but in other pregnancy problems, including its ability to aid 'controlled' convenience de liveries so-called 'babies by appointment.' You'll be hearing, too, of its po tential value in some stubborn diseases that have nothing to do with pregnancy But a terribly critical fact about the drug has to be faced. In the next 12 months there will be enough of it for only 20,000 of the 200,000 women who wil into premature labor and whose babies might be saved by it. It will be exasive. The drug is being introduced under unusual circumstances. Every tempt is being made to prevent hoarding, black market and waste," etc. Advertising Age, June 15, 1959, describes "Pharmony" as a means of clearing d hurdle for ethical drugs." "Sell it with music! and five commercials a ay in high traffic stores * * *. Five companies will be using 'Pharmony' in e promotion of Lederle Laboratories-Rhulispray, a treatment for poison ivy; ba Pharmaceutical Products-Nupercainal, an ointment for hemorrhoids; harles Pfizer-Visine, an eye lotion; Upjohn-Unicap, multipurpose vitamin; hering-Coricidin, allergy and cold preparation." Insulting to physicians' intelligence and contrary to good practice is the omotion of drugs for treatment of signs and symptoms regardless of cause. "In all diarrheas Creomycin, regardless of etiology."-Merck, Sharp & Dohme. Tachycardia-almost without regard to cause-can now be considered an dication for Serpasil."-Ciba. I wish I could remember whether it was Serpasil or Equanil (Wyeth) that as advertised to physicians in a series of full-page advertisements showing a hysician with doctor's bag walking on a city street, with caption "Doctors in . Louis (a different city each ad) Use '?'" whichever trade name drug it was. "Compazine stops vomiting in children-from virtually any cause."-Smith, line & French. Has enough been said or should one describe the advertisements of such as zulfidine (Pharmacia Laboratories) "the most widely accepted sulfonamide or treatment of ulcerative colitis. Administration of Azulfidine produces rapid gression of ulcerative and inflammatory lesions of the bowel. Remission or nsiderable improvement has occurred in 70 or 80 percent of the patients eated." Or Coldene, "a new idea in cold medicines. You're bound to feel etter almost at once-only $1 * * * Coldene is unlike any cold-and-cough medine ever offered over druggist's counters." Yet it contains phenopropanolamine ydrochloride, ammonium chloride, sodium salicylate, chloroform, and alcohol. r Revlon's Baby Silicare that "stops diaper rash before it starts *** Your by need not suffer from skin irritations again! *** Always clean and proet your baby with new Medicated Baby Silicare by Revlon! *** Your doctor nows Baby Silicare." Or "Senokot (Purdue Frederick) is the only standardized ecific large bowel neuroperistaltic which reproduces and restores physiologially normal evacuation, to provide both prompt relief and ultimate rehabilitaon of constitpated patients of all ages." A glance through the advertisements of almost any medical journal reveals shocking expenditure of money, time, and space in trying to influence physians by psychological gimmicks rather than by factual information that a doctor sing a drug should have. Think of the service to doctors that would result from evoting such money, time, and space to presenting concise data on absorption, istribution, degradation, excretion, pharmacological action, toxicity, and dosage. dvertisements would then be a valuable source of important information intead of what they too frequently are today. I can't believe Senator Hruska is unaware of such promotion as illustrated y the above examples. Yet he seemed to resent criticism of the drug industry relation to them and Senator Dirksen has implied that such criticism reflects lack of appreciation of the important contributions of drug companies in the rovision of increasingly effective therapeutic agents. I would like to emhasize our appreciation of these many contributions. We also appreciate the ompetitive pressures that require the prompt creation of a market for a new roduct so that development and production costs may be covered before a cometitor's newer product supplants it. We are aware of both the assets and roblems created by such competition and our purpose in testifying before your ommittee was and is to contribute to considerations of the latter that may lead o constructive action permitting fuller development of the former. Very sincerely, ALLAN M. BUTLER, M.D. [From Time, Feb. 27, 1956] DON'T-GIVE-A-DAMN PILLS As one of Groucho Marx's writers told it: an unemployed actor was interrupte at breakfast by his wife carrying a Dagwood sandwich of unpaid bills. "What I do with these?" she asked. Replied the actor, with a careless toss of the head "Tear 'em up and order some more Miltown." Miltown, one of the two trade names for meprobamate, the latest popular tranquilizing drug, has become the fastest-selling pacifier for the frustrated and frenetic. The backlog of unfilled orders is at once the pride and despair of Wallace Laboratories in New Brunswick, N.J., makers of Miltown, and Philadel phia's Wyeth, Inc., which calls the same drug Equanil. Hollywood is, naturally the hottest market. A drugstore at Sunset and Gower splashed huge red letters across its window when a shipment arrived: 'Yes, we have Miltown!" Most of the time, this and other drugstores are not so fortunate. Schwab's, Los Angeles best known, has dispensed 250,000 pills (both brands) from four stores in for months, and has turned away more orders than it has filled. For friends only.—The craving for the "don't-give-a-damn” pills is not confined to Hollywood. In staid Boston the demand is as keen, but less shrill. It is the same in New York City, Washington, D.C., Charlotte, N.C., and Houston, where druggists refuse to fill prescriptions for strangers, often have to limit regular customers to a dozen pills on account while they wait for an overdue shipment Developed by Wallace Labs' Dr. Frank M. Berger from a muscle-relaxing dra which had some incidental calming effect, meprobamate was not generally re leased until last summer. It was offered to doctors for treating walk-in neuroti rather than locked-in psychotics, with the assurance that it was free from the unpleasant (and sometimes dangerous) side effects of the earlier tranquilizers, chlorpromazine and reserpine. "No energy, of course.' -Outside Hollywood, few users advertise the fact that they are among the pill buyers. But in the unbuttoned movie colony, Kends Rocklen, movie columnist for the Mirror-News, reported: "I went from Ginger Rogers' party to José Ferrer's party to a dinner party, and everywhere they were talking about it. My husband is on it now. He used to be very nervous, resit, just miserable. Now, he doesn't get mad as quick or stay mad as long. He la no energy, of course." Says Milton Berle: "It's worked wonders for me. In fact, I'm thinking of changing my name to Miltown Berle." There is still little medical evidence as to how well the pills work. The many facturers report customer satisfaction in two-thirds to three-fourths of cases, bar there is no way of knowing how much of this is due to suggestion. One of the more convincing testimonials: Palm Springs Veterinarian Herman Salk (brother of Vaccine Maker Jonas Salk) reports that Equanil is dandy for neurotic dogs changes them in a couple of days from biting, man-hating monsters into lovab rovers. |