Document QYr79BNnrMb8Xwm63aQzLdVR

JOSEPH E KELLER JEROME H. HKCRMAN CHARLES M MEEHAN WILUAM II, HOHGHE5A.NI, JR ROBERT K TIERNAN WAYNE V BLACK DAVID L HILL MARTIN W BERCOVICI LELAND J BLAIR PETER M NEMKOV FEB 1 2 1973 LAW OFFICES Keller and Heckman 1150 17T" STREET, N, W. SUITE lOOO WASHINGTON, D-C. 20030 February 8, 1973 TELETHON E sos soo-s?oo CABLE ADDRESS KELMaN Dr. Karl A. Hochschwender American Hoechst Corporation Post Office Box 2500 Somerville, New Jersey 08876 Dear Karl: Following up in a general way on several of the matters discussed at our December 15 meeting, I thought it might be worthwhile if, firstly, we sent to you and all of the members of the Committee a series of three articles from the February 4, 5, and 6 editions of the Washington Post. As you will note, all three of the articles were written by Mr. Morton Mintz, a Post staff reporter who has become something of a consistent FDA watcher and analyst. Mr. Mintz' writings will, of course, speak for themselves. On occasion he has been a vigorous critic of the Food and Drug Administration but at this time he appears to be more on the side of defending the agency and its efficacy. The only reason I thought I would call this matter to the attention of our Committee is be cause I think it will serve to point up some of the comments I made at the December meeting about the fluctuating status of Washington opinion on the Food and Drug Administration, its present structure, and the possibility of future restructuring. The articles really do not deal with matters of direct interest to us since they focus on the drug situation primarily. What I think they do indicate is that the present way in which the Food and Drug Administration operates procedurally is being called into question by import ant spokesmen. This we consider to be quite healthy. It may even lead to significant changes at some point which could be of lasting benefit. ASI-PR 0001689 Dr. Karl A. Hochschwender February 8, 1973 Page Two For those who might be interested in my personal opinion, I think I disagree with Mr. Mintz' apologia for FDA, but I also disagree with the much publicized Peltzman-Friedman concepts. As I see it, both points of view represent extremes. What is really needed is a more effective regulatory body and my view is that this would best be accomplished if the Food and Drug Administration were reconstituted along the lines of the independent agencies such as the Federal Communications Commission and the Securities and Ex change Commission, both reporting directly to Congress, but otherwise operating independently. Rather than burden you with any more of my own philosophical feel ings, I will now leave this subject for you and the readers hereof to conjure with. Relative to other matters which might also be considered in the nature of follow-up items on our last meeting, we would like to direct the Committee's attention to two reports which appear in the December, 1972 edition of Food and Cosmetics Toxicology (Volume 10, Number 6). A brief description of the articles, which should serve to let you know why we think the members of the Committee might be interested in seeing the same follows: 1. The first article begins on page 815 of the volume in question and is entitled "Migration of Ad ditives from Plastics Films into Edible Oils and Fat Simulant." It was authored by K. Figge and relates to the report Dan Dixler and you gave more or less jointly relative to a synthetic triglyceride which may be used as a fat simulant. I suspect that most of our Committee members have ac cess to Food and Cosmetics Toxicology so we are not reproducing the Figge article here. We would suggest that anyone who does not receive this pub lication consider ordering the December issue by writing to Pergamon Press, Ltd., Maxwell House, Fairview Park, Elmsford, New York 10523. ASI-RR 0001690 Dr. Karl A. Hochschwender February 8, 1973 Page Three Perhaps it will be sufficient to give everyone a clue as to the signi ficance of the article by Mr. Figge if we simply quote here the second para graph of the Abstract of his paper: "The measurements showed organic solvents to be unsuitable as gen eral fat simulants. The migration values of an additive from a plas tics film into different edible oils were so similar that one edible oil could serve as a simulant for all others. However, the presence of other naturally-occurring substances makes the analytical determination of migrated additives in edible oils very difficult, so a synthetic tri glyceride mixture with extraction properties similar to those of coco nut oil was developed to serve as a standard fat simulant. Analytical studies with this fat simulant, HB 307, proved its advantages over coconut oil. Its suitability as a standard fat simulant was confirmed in migration tests." 2. The same edition of Food and Cos metics Toxicology referenced above con tains another report on BHT and BHA in the form of a lengthy article by J. R. Allen and J. F. Engblom of the University of Wisconsin, the article being entitled "Ultrastructural and Biochemical Changes in the Liver of Monkeys Given Butylated Hydroxytoluene and Butylated Hydroxyanisole." At least as we read this arti cle, it adds still further weight to the conclusion that presently permitted levels of these two important antioxidants are quite safe and that, for example, the socalled FAO/WHO acceptable dietary intake ASI~pp 0001691 Dr. Karl A. Hochschwender February 8, 19 73 Page Four for the use of 0.5 milligrams per kilo gram of body weight is a very conserva tive figure. I hope that this general information which we are supplying will be of interest to many of you. I might also take this opportunity to mention that you should be receiving your copies of the December 15 Minutes very shortly, if you have not already done so. The, reason I do mention this fact is because we have had a number of inquiries about the Minutes in the past several days and were surprised to hear that some had not received them in light of the fact that they were mailed by the SPI office at the end of January. I feel quite certain that the reason for the delay is because the mailing was made fourth class because the Minutes are quite bulky and it was, therefore, deemed prudent to send them by fourth class mail. In short, please be a little patient if you do not have your copy yet, but by all means let Charlie Condit know if you have not received the Minutes within the next week or two. Enclosures cc: SPI Food, Drug and Cosmetic Packaging Materials Committee ASI-PR 0001692 bltfultt), t i l/. lf l Uii \\ Anul.V; MJ_\ l`OM hould the e Dismantled? By Motion Mintz Regulatory agencies arc criti cised all the time for not enforcing the law the way one critic or an other thinks it ought to be enforced. This has been the lot of the Food and Drug Administration ever since the first federal food and drug law Only after a 25ycar fight was the first true federal pure food and drug law enacted, in 1906. The late Dr. Harvey W. Wiley, who led the battle, said that a "group of ghouls" had foisted on humanity "the most wretched and disgraceful evil": "quack medicines," mostly harmful, for winch manu facturers claimed therapeutic omnipotence. Wiley told of "headache powders" that addicted women, of "painkillers" that "usually depressed the heart of the victim" and "made the pain far worse," of cancer "cures." He told of mothers who innocently "doped their babies into insensibility at night with soothing syrups containing opium or morphine." was enacted in 1906. But for some l! 41 time now, the FDA has been a target for those who would cripple I it or abolish it altogether. II Most revisionist proposals enjoy brief publicity only to fade into ob scurity. Such was the fate of bills sponsored by Sen. Mark 0. Hatfield (R-Ore.) to transfer drug-regulatory functions from the FDA to the Wiley became the first head of what is now the Food and Drug Adminis tration. In 193S, the FDA acquired major new powers as a result of 107 deaths caused by "Elixir of Sulfanilamide," in which the solvent was a chemical relative of a radiator antifreeze. In 1962, the agency's powers were expanded anew in the wake of the birth of thousands of limbless Thalidomide babies abroad; only a few were bora here. But increasingly, frustrations with the FDA's performance have led some to urge possible repeal of the food and drug laws, reversing thephilosophy adopted 67 years ago. This is the first of two articles analyzing such proposals. National Academy of Sciences. Such was the fate of a proposal by Richard M. Furiand of Squibb sure the safety and efficacy of cedures used to evaluate and ap I Corp. to make the FDA "an inde medicines in the first place, rather prove new drugs stifle "creativity," I pendent regulatory agency report, ing directly to the President." Far more serious is a batch of than to the agency's performance in implementing the drug law. Last February, a group of scien increase research costs, reduce the number of new dings "and may be depriving the practicing physician pending lawsuits, some of which tists led by-Dr. Robert D. Dripps, of agents beneficial to patient care." are before the Supreme Court. vice president for`medical affairs The complaint deeply troubled These lay down a collective chal of the University of Pennsylvania, the FDA, partly for reasons that lenge to the fundamental legal right complained in a letter to Rep. Paul have nothing to do with its counter and capability of the FDA to as- G. Rogers (D-Fla.) that the pro charge that the complaint was factually inaccurate and invalid. One of the reasons for FDA concern is Rogers' position as chairman of the House Commerce Health : Subcommittee which makes j him a powerful figure | on Capitol Hill. Another1 reason is that the complaint was persistently and mas sively publicized by Medical Tribune, which is distnb- 1 uted free of charge to phy- ' sicians and which is sup ported almost entirely by pharmaceutical advertising. The FDA saw its plight take a drastic turn for the ' worse within the last few weeks, when its very justi fication for existence came under devastating fire in newspapers and magazines intended for the public at large, including the finan cial pages of The New York Times; Barron's, and News week. ASI-PR 0001693 1 Writer's in ouch of these 1 publications drew on a 1 single sour";?, a paper pre- >er.ted by economist Sam l Peltzman of the University I of California at Los An geles at a conference on ;e\v drugs at tlie University 'hicago. Hotli Robert M. .berg, editor of Barron's, and Milton Fr.oilman, the Newsweek columnist and University of Chicago econ omist, acclaimed the paper as `brillian1," llo-ter Klein, tin Aryu-. Research Co: p. economist vinting in 'J'he Times, termed the paper "outstanding." The basic question ad dressed bv Pcltzrnan ivas whether the public had benefiUed by the 1902 amendments to the ly.'IS drug law. For the most part, these amendments required manufacturers to provide substantial pro - marketing evidence of efficacy, in ad dition to the pre marketing evidence of safety required by the existing law. The amendments also tightened `tile requirements for safety and empowered, the FDA to act against false and mis leading promotion of drug's to physicians. Peltzman concluded that the amendments have done far more harm than pood '1 that the public would well served by their re peal. Professor Friedman went further, if not all the way. To comply with the amendments, "FDA officials must condemn innocent peo ple to death," he said in a full-pace column in the Jan. 8 Newsweek. "Indeed, fur ther studies may well jus tify the even mure shocking Conclusion that the FDA it self should be abolished." With or without "further studies." no one in govern ment today expects Con gress to abolish the FDA, j unless it does so in order to I replace it with another reg ulatory device. At the same time, Friedman, who has been urging abolition of the t FDA at least since 1968 1 without visible impact, this time set top FDA officials and even Capitol Hilt crit- j ics oE the agency shudder ing. The (^^r.ation, in part, is the c^Hpence in climate. Not long" ago, for exam ple, an aide to President Nixon, commenting, on his views of regulatory' agencies that oversee business, said, j "He's not going to go out | to find people who are big ger regulators, but people who want to deregulate." More fundamental in the ` Jreaction of even FDA's crit- ies to the new attack is the j knowledge that regulated industries of any kind pre fer tiip illusion of regulation , to the absence of regula- j tton: that is. a situation in j which -the public thinks it j is being protected by the government when actually the Great Seal of the Unit ed States is merely being atfixed to whatever indus- I tries want. "The part of ; wisdom is not to destroy j tire [Interstate Commerce] 1 Commission, but to utilize it," a railroad attorney coun seled as early as 1892. .Vs for the food and drug industries, (Friedman did not .suggest that food regula tion be saved should the FDA go under), t lie con cern is that the professor's altitude will give the in- j tries a big push toward il- lusory regulation. \ It becomes important, ! then, to examine Peltzman's j message. His paper is 125 ; pages long and was pre- i pared for economists, but, I fortunately, Friedman pro- j vided a layman's summary j in Newsweek (the accuracy ; of which was attested by : Pcltzrnan in a telephone in- j tervievv). Friedman said: !; "The stiffen standards ! . [set by the 1962 amend- j menls] had a spectacular J effect on the rate of inno- j vation. Tn the 12 years prior to 1962, 41.5 new chemical I entities'--that is, really new J drugs--were introduced on the average each year; in the next eight years, 16.1. And their introduction was delayed by two years on the' average. `Peltzman used highly j imaginative techniques to ! assign dollar values to the j benefit from suppressing , harmful drugs or postpon- ! ins the introduction of use- j ful new drugs ... To make j sure that his resnlfSjj^uM hold up, lie leanc|BJvcr backward, oveiwtatin^acno- fits from the stricter stan dards, and understating costs. And, of course, he recognized full well that dollar estimates arc a pale reflection of the human benefit and harm in terms of lives saved and lost. But that seems the only feasible way to get a numerical : 1 measure that combines the value of comfort gained by ; relief of a minor distress, 1 days gained by avoiding or j , shortening illness and lives : gained by curing a hitherto ' ; deadly disease. \ "tie estimates that the | 1902 drug amendments cost | consumers of drugs--over | and above any benefits-- i S230 to S500 million per year I at a very minimum. Tliis is 5 to 10 per cent of the money j' spent annually on drugs. It ;: is as if a 5 to 10 per cent ; ' tax were levied in drug ' : sales and the money so raised was spent on invis ible monuments to tne late Sen. Kcfauver. | "To supplement this esti- ' mate, and to get some idea j of tlie effects of regulation on , the more dramatic mistakes j and discoveries, Peltzman _j examined the costs to sod- : ety of a thalidomide-type mis- j take, the benefits to soci- | ety from a penicillin-type t success (though the actual I examples lie uses include j Jneither thalidomide nor pen-' icillin), the frequency of j such occurrences prior to | 1962, and the areas, notably j heart disease and cancer, \ where major discoveries are j much needed for the future, j He then makes the extreme I assumption that no major i innovation will be perma- | I nently kept from the mar- j j j ket by the post-1962 proce- | dures, that their only effect * | will be to delay an innova- | ! tion by two years. Even with ; tliis extreme assumption, it | turns out that the cost of j delaying a beneficial inno vation is something like 10 to 100 times the value of avoiding a thalidomicle-type mistake. In human terms, the effects of the introduc tion of the drugs that con quered tuberculosis are dra matic. Peltzman estimates that postponing their intro- [ duction for two years would have meant about 45,000 ad ditional deaths from tuber culosis, and twice that num- \ ber of additional persons 1 with tuberculosis, out of a j much smaller population j than today's." | PeRzman's analysis ana ;j Friedman's use of it grow out of a shared, fundamen tal economic assumption; Tim best of all regulators is the free marketplace m which the consumer, through the choices ho makes, is sovereign. Few question (at least openly) the application of the consumer-is-king doc trine to those areas of the economy in which he has the information a sovereign needs in order to reign. But Congress decided long ago that consumer sov ereignly and caveat emptor --let the buyer beware__ are fatally deficient protec tors of the public in those areas of health and safety in which consumers cannot possibly be adequately in formed. Advancing technology has only served to persuade Con gress that it was right the first time around. Caveat emptor, for example, does not protect consumers from beef containing a cancercausing growth stimulant in amounts so tiny that they can be detected only with radioactive tracers. Con sumer sovereignty, whatever it may mean to economists, was of no use to blacks who for years were exposed to excessive radiation by Xray technicians bizarrely in structed by textbooks and manuals that higher dose"; were necessary for "Ne groid" persons. The explanation for Con gress's attitude is nowhere plainer than in the volumi nous public record in the prescription-drug field. Here, as the late Sen. Estes Kefauver (D-Tenti.) said, he who orders (the physician) does not buy, and he who buys (the consumer) does not order. That is to say, Congress recognized that; the layman, even when not incapacitated or uncon scious, lacks the information he needs to prescribe for himself, and must be at the mercy of the physician. The doctor, consequently, be comes the "consumer" ev en if it is the patient who goes to the pharmacy. That is why the prescription drug industry spent S500 million to Si billion last year (de pending on whose estimate is used! to promote medi cines to its market--200,000 prnetic'uq physicians. ASI-PR 0001694 2 J Friedman mentioned the thalidomide episode more or less in passing, omitting mention of a few salient points. This sedative in foreign countries caused the birth ot an estimated 10,000 limb less babies. No counterpart for anything quite so awful has been shown to have re sulted from the FD.\ pre venting any drug from reaching the market. In the United States, had thalidomide not been kept from going on sale, an esti mated 10,000 American in fants would have been born without arms or legs. The company that had been pres suring the FDA's Dr. Fran ces O. Kelsey to release thalidomide meanwhile was claiming that it had `-firm ly established the safety" of the drug with ``both foreign and U.S. labmatory studies," The ultimate ``buyer" tbit would have to "beware" was the fetus. How would it use caveat emptor to protect itself against a chemical passing through the pla cental barrier of a mother who got thalidomide from a physician who bad been mis led by the manufacturer, knowhngly or not? The deformaties caused by thalidomide could hardly have been more obvious. Moreover, the cause of the deformities was relatively easy to trace. Yet in sev eral countries without reg ulatory mechanisms, Isales of the drug continued un interrupted for weeks and even months after a causeeffect relationship had been established and widely pub licized. Suppose that thalidomide had caused cancer raUier than gross deformaties. Be fore Lhis would have been detected possibly 20 years would have elapsed. By that tune, probably no one would have been able to pinpoint the cause. Indeed, it was only through a stunning piece of recent medical de tective work on a rare form of the disease that a link was demonstrated between the ingestion of a hormone called DBS by women seek ing to prevent miscarriage, and the occurrence of va ginal cancer in their daugh ters up to a quarter-century later. Again, it was the fetus that was tha `consumer" and that supposedly was ex ercising "sovereignty." MONDAY: Threatened Pro tection1>) ASI-PR 0001695 THE TASIIIXGTOX POST ,, -Mnnrlny, Feb. 5,1973 g3 ! I Analysis The FDA: Battling and Embattled (Second of two articles on the question Of whether the Food and Drug Admin istration should be abolished.) By Morton Mints Are we not "fed with the same food, hurt with the same weapons . . asked Shakespeare's Merchant of Ven ice. "If you prick us, do we not bleed?" Pharmaceutical companies, in most respects, are like other companies. They do business, prize invertor confi dence, try to increase profits. They also try to expand their markets, as do other ventures. This particular activity is extraordinarily restricted, because it is not possible to expand markets for medicines by creating genuine dis eases. Yet drug houses have found ways to cope with this problem. If, for example, a drug is inade quately tested, or is fraudulently tested (the Food and Drug Administra tion and congressional investigators have documented numerous cases of each), the product may be prescribed by doctors who have been erroneously fed to believe that the product is safer and more effective than it truly is. More frequently, market expansion takes the form of exaggerated, mis leading and false or even simply un-' wise advertising and promotion of pre scription drugs to the physician Several times, the FDA has criminally prosecuted drug companies' for false and misleading claims of safety and ef ficacy. On other occasions the agency has used another weapon, seizure of in terstate shipments. Literally dozens of times, the FDA has forced manufactur ers to admit in corrective letters to doctors or in corrective advertisements that they have overstated safety and efficacy and understated risks and. dis- . advantages. In one criminal case, a drug for pre menstrual tension was claimed in ads in the journal of the American Medical Association to have no "contra indications," that is, no medical con- I 4 * ditions in which it should not be used. Actually, the manufacturer had acknowledged contra-indications in mil lions of official prescribing brochures. One of the civil cases developed from a Sl-million promotion falsely claiming that a drug approved for an gina pectoris had been shown to im prove the survival rate of hospital heart-attack patients. A corrective letter was sent by a company that recommended a semi synthetic penicillin for infections for which other safe and effective drugs were available; the danger here was that overuse of the semi-synthetic threatened to defuse a major reserve weapon against outbreaks of staphylo coccus bacteria, which can cause se vere and sometimes fatal infection. Physicians, influenced by drug com pany promotion, even now are continu ing the practice of so massively overprescribing and misprescribmg antibi-' otics as to imperil the health and sometimes even the lives of millions, specialists testified on Capitol Hill last December, All of this points to a fundamental question about a recent economic anal ysis by Sam Peltzman, an economist at the University of California at Los An geles, which is being used as the basis for renewed suggestions that the FDA should either be abolished altogether or should be stripped of some of its major protective powers, Peltzman's basic criterion for deter mining whether a drug was bad or good was simply the decisions doctors make in the marketplace. If over a long period of time they continue to prescribe a medicine, if it withstands the "ultimate test" of time, then by Peltzman's reckoning it is "good." "1 wouldn't feel disturbed if a doctor relies on that information which he thinks is most reliable," he told a re porter. ASI-PR 0001696 4 ne uui not, tie s-aiu, u-e mi^U civutu as was used in the l"30s by the^lfiA when a panel of 30 specialists, re^Hd by the National Academy of Sciences, found that physicians were irrationally prescribing antibiotic combinations, thereby needlessly inflicting hundreds of thousands of injuries a" year and threatening worldwide disaster from the proliferation of treatment-resistant organisms. Unlike economists such as Peltzman, scientists decades ago rejected the pro position that the impression of physi cians can be a tolerable substitute for adequate, well-controlled, bias-free studies done by experts. , "The average practicing physician-- and I have trained hundreds of them-- just does not have the time, the facili ties, the skill nor the training lo be an expert in the determination of drug ef- fieacy," Dr. Louis S. Goodman, a lead ing pharmacologist and member of the Council on Drugs of the American Medical Associaton, has testified. Among, say, 100 patients with pneu- . mocorci pneumonia, about 30 will die and the rest will recover without the ' use of any specific remedies. Suppose ; a physician prescribed aspirin, which has no effect on the recovery rate, and the patient recovered. This would "mean nothing with regard to the aspi rin because seven times in 10 the pa tient would have recovered anyway," says a former chairman of the council, Dr. Harry F. Dowling. In survey after survey, physicians In large proportions have been shown to be guided principally in their prescrib- ing decisions by advertising and sales pitches of drug companies that began giving them gifts to win their favor while they were medical students. This sort of influence has heen diag- nosed as probably the principal expla. nation for phenomena such as the needless deaths of thousands of per sons, mainly children, who have been prescribed a powerful antibiotic, chlo- ramphemicol, for conditions (such as colds) in which it is ineffective, or for , diseases in which safer agents are 1 available. ! Questioned about why they have pre scribed chloramphenicol, physician* have cited long experience in their pri- i vate practices with the drug, on/the 1 basis of which they have pronounced it ' "safe." j But from experience with, say, a few ; hundred patients, how would such a physician know that chloramephenicol kills one user in 24,200 to one in 40,500, depending upon dose? How could he learn contemporaneously, if ever, if an other drug were say, to cause cancer I 20 years after it was administered? The annual toll of adverse drug reac tions requiring hospitalization has been put by the National Center for t Health Services Research and Develop ment at 1-5 million, of which 30,000 are estimated to be fatal; the added medi cal expenses amount to at least $1,1 billion Repeatedly, in unrebutted arti cles and testimony on Capitol Hill, drug specialists have pinned major re sponsibility for this toll on physicians who prescribe on the basis of industry advertising and promotion. A lurllKT question about the comum tcr.ee of practicing doctors to as^B medicines is the ted of time tioned by Reltzman. Tile record, how ever, is replete with examples of worthless drugs that have passed that test. Archaic medicines such as strych nine continued to be prescribed "50 years after it has been established that tney have no use in medicine," Dr. Walter MocSell, a noted pharmacolo gist, pointed out in 1%2, During the 1930s large numbers of Southerners, denied a wholesome diet, fell victim to a serious disease called pellagra. Victims who went lo bed and ate the very kind of diet that produced pellagra seemed, at a certain acute stage of the disease, to improve briefly. "Any treatment, any procedure used at such a time is followed by this nonspecific improvement," Dr. William B. Bean, a specialist in pellagra, has said. "Thus, everything that was ever used by physicians, and this included almost every drug available in the pharmacopoeia, was praised as a spe cific cure." i j Citing the reltzman analysis as an argument for the possible abolition of the FDA, University of Chicago economist Milton Friedman charged recently in a column in Newsweek that the Kefauver-Harris Amendments to the drug law, enacted in 1962, have hurt the public by delaying the advent of valua ble new drugs. (The amendments tight ened safety requirements and required manufacturers to provide more pre marketing evidence of safety and efficacy.) ' | The implication is that new drugs are necessarily better than old ones (and, of course, better than none at all; Friedman does not discuss the possibil ity that other therapies such as acu puncture may have their uses but, of fering no profit for a major industry, long go ignored). But the record suggests that new drugs are sometimes worse. Often the , FDA has allowed a new drug to go on sale, seen it exuherantly promoted to doctors, seen doctors exuberantly pre- ; scribe it--and then had to recall it because it was discovered to be doing J more harm than good. A memorable example was an anti- j cholesterol drug called MER/29. The i FDA finally had to take it off the mar- i ket in 1962. Eventually MER/29 proved to have caused a classical triad of irtju- 1 ries--cataracts, loss or thinning of hair and severe skin reactions--in thou sands of persons. Other drugs continue to be mas sively prescribed today although some eminent scientists retain doubts about them. The FDA allowed efficacious oral contraceptives to go on sate without requiring their safety to be demonstra ted. Not until several years later was it established that the pills cause blood clotting diseases in some women. Might the pills have genetic effects on the offspring of former users? Might the estrogens in them cause cancer? The tests that would provide the an swers have not been done. In a letter countering the Friedman position, FDA Commissioner Chari'- C. Edwards said that the decline in the rate of introduction of r.ew drugs, blamed by Friedman on the amend ments, actually began some years be fore the yvvere enacted. "Moreover, the decline has been worldwide, encom passing some nations that as yet do not have these requirements," Ed wards said. Recalling Friedman's use of an ex ample of deaths attributed to a two- year delay in the introduction of a tu berculosis drug, Edwards said the ex ample was "hypothetical, it never nap- pened, and l am convinced it never will." He went on to say: . . No Americans are being con demned to death or misery because im portant drugs are being held up. There are no miracle drugs available in other countries that are not available here, I am not aware of even one life-saving drug entity whiqh is not available here because of our more stringent safety standards. Nor is research being sti fled. Drug research is, in fact, healthy and growing. We have repeatedly chal lenged our critics to name one impor tant drug development which is availa ble outside the United States but not here. We have had no takers. We sub mit the same challenge to Newsweek's Mr. Friedman." Friedman's reply to the challenge was published with Edwards' letter in Newsweek. After accusing the commis sioner of a "bureaucratic conditioned reflex" barren of "a single fact in re ply to my column," the economist of fered examples of drugs available ' abroad but not here, "praetolol and Oxyprenolol, to mention just two im portant in cardiology." The FDA acknowledged to a re porter that the two drugs show prom ise for treating serious, irregular heartbeat; noted that no American pharmaceutical firm is doing the clini cal testing needed if the drugs are to be given general approval;,and pointed out that physicians can obtain the drugs on an experimental basis for treating patients who do not respond to a marketed remedy called Proprano lol- But there is a question that the FDA says it must face: "Are we able to rule out the hazard of possible cancer?" The agency's Cardiovascular and Re nal Advisory Committee, composed of medical experts in this speciality, "has recommended that the drugs be admin istered to patients when Propanolol or other treatment is not effective," the _ FDA told a reporter. But, it said, the committee also has recommended "further studies to evaluate the true nature of the cancer factor connected with these drugs." / ASI-PR 0001697 5 Test Rules Defended By FDA \ By Morton 7\Tintz Washington PojL Wvi*er . The food end Drug Admin istration, mounting a major counterattack on a new wave I of critics who would weaken or even abolish it, test)tied yesterday that its strict rules for human trials and market ing of prescription drugs spared the United States frum several calamities that occur red abroad. A medicine for victims of bronchial asthma, never sold here, was linked to "an epi demic of deaths'' in England and Wales during the l!)SQs, < the FDA told a Senate hear ing. The agency said it blocked mai lading of a weight-redue- i inq drug even before recent studies associated it. with an "epidemic" in Austria, Ger many and Switzerland of a sometimes fatal lung disease that had been rare everywhere | until the late 1960s. | Among about 25 other medi- 1 ernes that never made it to the American market were a drug to lower blood pressure that | caused liver disorders in 84 j per cent of those who ingested 1 it, and a tranquilizer that : caused similar disorders in 43 per cent of its users. ! FDA Commissioner Charles C. Edwards and top aides as- ) sembled the evidence, much of ; it previously undisclosed, to i rebut charges that Americans are being deprived of impor- ' ,tant new safe and effective l drugs available elsewhere, and j that the agency's implementa- I tion of drug-law amendments i enacted in 1962 has decreased the number of important new drugs entering the market. Sen. Gaylord Nelson (D- Wis.), chairman of the Monop oly subcommittee, opened a'- four-day hearing on tho devel-; opment and marketing of newj drugs by declaring that those , who made the charges have a! "duty" either to document orj withdraw them. j One of the critics, Dr. Roh-: ert D. Dripps, vice president; for medical affairs of the Uni-j versify of Pennsylvania, has- said he is too busy to testify, Nelson disclosed. Another critic is economist Sam Peltzman of trie Univer sity of California in Los Ange les, author of a widely ac claimed paper calling for re peal of the amendments. Tuea<Uyjm.t,V>T3 Tills 'WASHINGTON POiT FconorTlist Milton Friedman I of the University of Chica-ol used the Peltzman analysis to step up the attack on the FDA to what Nelson termed "the E. Simmons, director of the point of irrationality." Nelson FDA's Bureau of Drugs, testi cited Friedman's column in fied. the Jan. 8 Newsweek charging The medicine, a concen that tile amendments force the trated, potent aerosol spray FDA to "condemn innocent called isiproterenol, wa3 mar people to death." Friedman keted in the 1960s, under vari suggested the public might be ous trade names, by several belter off were the FDA to be abolished. companies in rope. Britain and Eu The amendments require In England and Wales alone, manufacturers to provide sub use of the drug was associated stantial evidence of effective by Dr. Paul Stolley of Johns ness in the form of well-con Hopkins with a "seven-fold in trolled clinical investigations, crease in asthma mortality in require informed consent only seven years," with 3,500 from persons in drug experi "excess" deaths, and with 7 ments and tighten safety re per cent of all deaths in child quirements. ren 10 to 14 years of age, Sim The asthma medicine was mons testified. responsible for ,what "may The FDA official said Stol well be one of the greatest re ley determined that .the corded therapeutic disasters "epidemic" was averted in the in modern history," Dr. Henry United States because the drug was not licensed here. Actually, no manufacturer sought marketing approval. Had one done so, Simmons said, he would have been re i quired to provide a pre-mar keting demonstration of safety of American Home Products! and efficacy with careful ani Corp, as Sordinol. In newborn i mal and human trials. The dogs the drug increased the spray continues to be sold fatality rate and in. rodents it abroad. caused cleft palate, Simmons The weight-reducing drug reported. Animal tests can sig linked to an epidemic of lung nal risks for humans. disease is aminorex, sold as Geigy's Opopramol, sold in Menocil by' the Swiss subsidi 54 counties, for the treatment ary of Johnson & Johnson's of mild symptoms' of mental McNeil Laboratories. Simmons testified that the (disturbance, was tied to ad FDA began monitoring the ex verse effects on the reproduc-j perimental use of aminorex in ;tive systems of three animal! 1962 but never allowed it to go species, Simmons said. In hu on sale. Switzerland approved mans it was related to blood it for sale in 1965. Three years later, the FDA required the and liver disorders and a syn drome characterized by large McNeil firm to halt human blisters of the skin and mu testing, "thus preventing a cous membranes and damage!' needless tragedy in this coun to internal organs, | try which might have occurred with widespread long-term use," Simmons said. The drug to lower blood pressure, guanoxan, was on an FDA list of about 25 medi cines currently sold abroad but barred from further hu man testing and marketing in the United States. Guanoxan, sold abroad by the Pfizer Co. under the trade- name Envocar, had side ef fects severe enough that 31 of the patients on it "had to dis continue therapy,'' Simmons said. The tranquilizer associated with liver discorders in 43 per cent of its users was identified as clopenthixoi. sold by the ASr~PR 0001698 Ayerst Laboratories division