A PATENT HUSTLE

...Others don't even bother to buy medicine they need because the price tag is too high...

...Shedden knew about the four jaundice cases but didn't mention them because of a technicality: They weren't in the group of 2,200 that he chose to write about...

...Products protected by patent tend to cost more than corresponding products subject to marketplace competition...

...Many [old people] now face the choice between medication and food or other vital necessities," Representative Albert Gore, Tennessee Democrat, said in September, pleading with House colleagues not to suspend the rules for patent extension...

...If 49.4 per cent of the fruits of R&D consist of products that "duplicate a drug marketed in the U.S...

...Shacknai went on: "For those who would delay and obstruct reform of the new-drug approval process, Oraflex—which must be seen as an aberration—may become a code word...

...Old people are sicker than younger people, as a rule...

...But the drug lag story goes on...

...Drug regulators and drug companies, he suggested, should be partners, not adversaries...

...Only 2 or 3 per cent of all drugs brought to the FDA serve any valuable new purpose in the national medicine chest What the Las Vegas doctor and his patient did not know—but what Lilly understood perfectly well by this time—was that deaths from liver failure after Opren use had already been reported in Britain, where the drug had been in use since October 1980...

...For those injured parties, the opponents suggested, the clock could be halted during the purely bureaucratic phase of the procedure...

...Just about half were what the trade calls "me-too" drugs: chemical molecules that were given a trivial twist to qualify technically as a new drug but actually duplicated drugs already available...

...It never got a chance to do its dirty work in this country...

...Four million elderly Americans spend more than $150 a year each, and some 750,000 spend more than $375...

...The other assumption is that the wheels of bureaucracy grind too slowly to serve the public interest...

...Its availability over there and its nonavailability over here was taken by many gullible people as evidence that there was something to the charge that bureaucrats in the Food and Drug Administration (FDA) were denying Americans medical relief that the ill of other advanced nations enjoyed...

...FDA leaders are fulfilling their mandated responsibilities as expeditiously as possible under current regulations...

...For the less conscientious elements of the media, Lilly had its Oraflex message already packaged in print and audio form...

...Adjusting for inflation, OTA found that the drug industry between 1965 and 1978 increased its constant-dollar outlay for R&D year by year without exception, going from $356 million (in 1967 dollars) in 1965 to $655 million in 1978...

...Between May 19, when it went on the market, and August 4, when Lilly "voluntarily" withdrew it in the face of growing evidence of its lethality, benaxoprofen had been available in the United States for just seventy-seven days...

...In fact, FDA has for several years maintained a "fast track" for approval of drugs that promise important improvements in health care...

...But even with generics available, the big brand names still sell at many times the price of the unbranded competition...

...So much for the need for "patent term restoration," as the bill's advocates refer to it...

...As the Ninety-seventh Congress drew to a close this fall, the drug-makers came within an ace of winning a special benefit under a patent proposal that would Judith Randal and William Hines write about health and science issues from Washington, D.C...

...And finally, it is primarily a disease of aging—important in a country where the elderly are the fastest growing segment of the population...

...In that eight-year period, 257 out of 717 new drug applications (NDAs) approved were for "new molecular entities" but only twenty-one of these were regarded as important therapeutic gains...

...Many drugs, in fact, are protected for far more than seventeen years by virtue of multiple patent claims filed in the course of the drugs' marketing lifetime...

...There is no evidence that the FDA approval process is biased against valuable drugs and in favor of trivial ones, so the logical conclusion is that only 2 or 3 per cent of all the drugs brought to the FDA serve any valuable new purpose in the national medicine chest...

...Not our nation's elderly, poor, and chronically ill, but large drug companies who cry for more protection...

...Bailing out Lockheed and Chrysler may be defensible—as bailing out the pharmaceutical industry might be if it were about to go belly-up...

...Just after Oraflex was withdrawn, The New 381 NOVEMBER 1982 York Times on its op-ed page published the views of Jonah Shacknai, counsel of a House drug oversight committee and onetime member of the Congressional Commission on the Drug Approval Process...

...This drug has been found to damage eyesight in some patients, result in permanent or near-permanent blindness, and to induce the growth of a strangulating membrane in the bowels of others, some of whom died undergoing remedial surgery...

...If Oraflex truly did not have any effect on the liver, it would be a new type of NSAID indeed...

...This characterization, from the FDA's New Drug Evaluation Project briefing book for May 1982, suggests that something over $3.5 billion in 1967 purchasing power (roughly $7 billion in today's money) has been spent copying someone else's product or designing a prettier package to put it in...

...It is chronic...

...All this time, the U.S...

...In fact, NSAIDs have proliferated so rapidly—particularly in the last six years— that according to the physicians' magazine Medical World News, even doctors who specialize in the treatment of rheumatic diseases don't know how to match drugs to patients for optimal results...

...Some critics think the track is too fast...

...Even Time magazine, no stranger to sensationalism when it suits its purposes, fanned the fires of patient demand with a glowing appraisal of Oraflex...

...One of the more spectacular plays given the Oraflex story came in the National Examiner, a checkout-counter tabloid...

...One is that Americans are being denied important therapeutic advances, though they are available to other industrialized peoples...

...Though the medical profession is increasingly disturbed by this sort of directto-patient hustle, the practice is ever more common...

...Vice President George Bush, who heads Reagan's regulatory task force, spoke glowingly of this trend in a speech last summer to an international gathering of pharmaceutical manufacturers...

...This same George Bush was, in private life, a director of Eli Lilly & Co., those wonderful folks from Indianapolis who gave us Oraflex...

...Translating an idea into tangible use takes time, the more so now that product liability is a major consideration in any manufacturer's decision-making process...

...These included such gold mines as Lilly's Darvon (propoxyphene, by generic classification) and Roche's Librium (chlordiazepoxide...

...But the drug companies have been—along with the oil and tobacco companies—consistent top money-makers in American industry...

...A medication for boils called Stalinon caused an epidemic of toxic brain disease and the death of many patients in France...

...But it is not the only one...

...Relaxation of efficacy criteria would, of course, make things considerably easier for the drug companies...

...More recent arguments in favor of the extension have shied away from the question of injustice to the drug companies and moved toward a claim that the public is suffering under the status quo because existing patent law stifles research and development...

...The industry has already received a powerful incentive to innovate in the form of a 25 per cent tax credit for R&D...

...HoffmanLaRoche was not prepared to go ahead with mass production of the drug quite as quickly as FDA was able to move...

...The rationale was that the drug companies are accomplished timewasters themselves where it suits their convenience, and in addition their patent attorneys are clever about getting around time limitations...

...A study made in 1979 revealed that four drugs that had been off patent for three to fifteen years still accounted for 86 to 95 per cent of the sales in their generic category...

...As a matter of fact, even before these deaths were reported, Lilly learned of four cases of jaundice following administration of the drug in clinical trials here...

...Proponents of the patent extension turned a deaf ear to these arguments in the House Judiciary Committee, which reported it out favorably to the full House...

...We cannot hold the FDA morally culpable for Oraflex's aberrational side effects...

...But if the two assumptions can be shown to be false, then the presumed need for reform can be dismissed...

...Hired physicians are fielded, like detail men of earlier days, to spread the word with the authority that only a white coat can confer...

...Government did absolutely nothing, despite pleas, threats, and finally the filing of a lawsuit to compel Health and Human Services Secretary Richard S. Schweiker to declare the drug an "imminent hazard...

...Arguing that an important fraction of a typical drug's seventeen-year patient life is wasted while FDA spins wheels in the approval process, the industry dreamed up what came to be called the Patent Term Restoration Act...

...In other words, the drug lag may be closing, but not in the way American advocates would like to see...

...But its campaign for patent extension proceeded through the summer of 1982 as though the tax credit had never existed...

...Despite Lilly's claim that she must have had an undetected congenital liver defect, her doctor said he had given her a complete liver workup before agreeing to prescribe the drug, and had found her liver in perfect condition...

...Nowhere is this more evident than in the drug business, where compounds protected by patent often sell for five to ten times the cost of manufacture during the patent life, only to drop sharply in price when generic brands become available...

...Opponents of the pharmaceutical industry's effort to win longer-lived patents argue that even without an FDA gamut to run, a prudent drugmaker would have to do most of the pre-marketing safety tests just to cover himself against future damage suits...

...In show business, it is known as hype...

...The FDA can only be asked to exercise prudent judgment based on the best available scientific knowledge...

...Right above the Hitler Is Alive headline was a large blue-and-white display box bearing the words Arthritis—sensational new drug...

...Wolfe and Gordon noted in an aside, "Ironically, the economist Milton Friedman cited this drug as an example of drug lag...

...Even the lapse of a patent does not necessarily end the gravy-train ride of a wellpromoted drug...

...Actually, as FDA statistics indicate, there is plenty of innovation going on in the drug industry—but not very much of it is honest change...

...Any increase in the cost of medicine will fall disproportionately on this large and growing part of the population...

...Never has a medication, once withdrawn by its maker, "voluntarily" or otherwise, been reapproved by the Food and Drug Administration...

...A survey of FDA consumer-protection activities (recalls, warnings, and the like) during eighteen months of the Reagan Administration shows a decline of two-thirds from a corresponding period of the Carter Administration...

...Thalidomide is the classic—some say overused—example of how drug lag worked to the advantage, not disadvantage, of the American consumer...

...In the multi-billion-dollar pharmaceutical industry, this is known as bringing information on important new therapeutic advances to the attention of the public...

...Wolfe and Gordon have noted a trend in Europe toward tightening, not loosening, drug licensing laws, suggesting that these countries are becoming more aware of possible problems with drugs, especially longterm use, and they are moving toward stricter regulation...

...In the House Judiciary Committee, where Chairman Peter Rodino from the drug-making state of New Jersey was a forceful advocate of patent extension, opponents acknowledged that there might be Some critics suspect comers are being cut on both the safety and efficacy provisions that govern the licensing of drugs instances where FDA foot-dragging deprived a company of just property rights in its patent...

...If anything, the Senate version of the patent bill, passed in secret in 1981, was even more outrageous than the House's...

...Manufacturers are still complaining of bureaucratic red tape that withholds important drugs from the American marketplace, though there is little evidence to support the assertion that a drug lag really exists...

...There is a move afoot to send pharmaceutical medicine, if not "back to the leechers of the Dark Ages," as Shacknai put it, back to the pre-Kefauver Amendment days when a drug did not have to be proved efficacious to win FDA approval...

...A patent is, pure and simple, a monopoly—a license to prevent others from making money from a useful idea for a certain period...

...Other countries allowed the drug on the market but later withdrew it completely...

...market...

...One of the most heavily lobbied pieces of legislation in recent years ($378,257 in campaign donations by twenty-two pharmaceutical industry political action committees in the first eighteen months of the Ninetyseventh Congress), the measure supposedly would stimulate research and development and thereby improve the therapeutic position of American medicine...

...As a matter of fact, most of the drugs approved by FDA are not therapeutic advances at all...

...Small wonder, then, that eighteen arthritis remedies of a class called nonsteroidal anti-inflammatory drugs (NSAIDs for short) have been developed and approved for use in this country...

...It is painful, so sufferers are continually searching for relief...

...The withdrawal of Oraflex closes one chapter of the drug lag story...

...One study showed, for example, that twelve big-selling drugs with aggregate 1980 sales of almost $1.4 billion actually are under market protection for an average of 18.5 years, and that five of them (Valium, Aldomet, Diabinese, Mellaril, and Zyloprim) have protection for twenty years or more...

...This caveat was a gross distortion of the facts: For one thing, alone among the NSAIDs, Oraflex has been found during clinical trials to induce an excruciatingly painful hypersensitivity to sunlight and a condition called onycholysis, in which the fingernails separate from the nail beds...

...It is debilitating but rarely fatal...

...Darvon's wholesale price is more than six times that of the cheapest generic propoxyphene, and Librium's is almost sixteen times that of the cheapest chlordiazepoxide...

...Less than a month later, she had the distinction of being the first American to die of liver failure as a consequence of taking the drug...

...by another firm" and represent "little or no therapeutic gain," what public benefit is derived...

...a mild discoloration in skin and nails when exposed to sunlight," in the words the National Examiner lifted from a Lilly press release...

...have extended lucrative drug monopolies for an additional seven years...

...The "drug lag" propaganda is only part of a continuing campaign by one of the most profitable industries in the United States to enrich itself at the expense of the sick and dying...

...Diabinese, approved in 1958, will not see the last of its patents expire until 1984, and Mellaril, first approved in 1959, will still be protected in 1983...

...This represents an 84 per cent increase in real spending for R&D during a period when the industry complained that research was drying up...

...One person who read or heard these reports was a forty-seven-year-old woman in Las Vegas, Nevada, who went to her doctor early in June and asked for Oraflex...

...When the FDA gave its approval to Oraflex last spring, Eli Lilly & Co...

...Oraflex was the seventeenth of the NSAIDs to win approval...

...The list goes on...

...It will be raised as a barrier, like thalidomide, that brooks no discussion and ends all arguments...

...In eight years between January 1, 1974, and the end of 1981, only 5.3 per cent of drugs approved were classified by the FDA as "important therapeutic gains," and only 13.2 per cent as "modest therapeutic gains...

...By definition, people who take medications are sick—or at least think they are...

...of Indianapolis launched the drug in a blaze of publicity appropriate to a California supermarket or Detroit's Big Three automakers...

...Many more will suffer if we prolong the protection of expensive brand-name drugs, keeping lower-priced generic equivalents off the shelves...

...In the case of an arthritis drug like Oraflex, hitting the public is particularly desirable from an industry point of view...

...From this argument easily flows the conclusion that "reform" is needed...

...The FDA has refused to approve it for the U.S...

...The other is that a constipated bureaucracy, operating under the strictures of an overly persnickety law, is to blame for unconscionable delay...

...The over-sixty-five population represents 11 per cent of the total but consumes 25 per cent of the medication taken in this country...

...Radio stations, most of them small, understaffed, and perennially hungry for air fare, played Oraflex messages in the guise of news items right off the "Eli Lilly Arthritis Hot Line...

...Accutane had been approved four months earlier, but so swift had been the FDA approval process that it caught the manufacturer by surprise...

...It was enough, before 1962, for a drug to be safe— although by no means all pre-1962 medications were as innocuous as one might suppose...

...Like most legislative proposals that will not survive the full glare of public debate, this one was sneaked to a voice vote in the Senate in mid-1981 with only a half dozen or so Senators on the floor (the absence of a quorum thoughtfully not being suggested by any of those present...

...The average senior takes more than six different drugs and spends $109 of his or her scarce funds each year for medication...

...But even this argument does not wash...

...A PATENT HUSTLE The drug makers' hype has serious side effects BYJUDITH RANDAL AND WILLIAM HINES The anti-arthritis medicine Oraflex isn't exactly what the pharmaceutical industry has in mind when it talks about the "drug lag," but it is something of an example nonetheless...

...It never was approved in the United States...

...Physician Sidney M. Wolfe and economist Benjamin Gordon of the Public Citizen Health Research Group cite another instance of beneficial drug lag, involving a British heart drug called practolol: "Shortly after its introduction, so many serious side effects were reported that its use was restricted severely...

...In the guise of encouraging future R&D, it granted holders of existing patents an extension—a novel grandfather clause that added up to nothing more than a giveaway to industry...

...If there is a drug lag, it may be attributable to the American regulatory code, the toughest in the world...

...What distinguished these radio spots from outright commercials was that Lilly did not have to pay for them...

...As Shacknai made clear, the drug lag argument is predicated on two assumptions...

...It would be tragic if, in the name of preventing 'another Oraflex,' reforms aimed at ending the drug lag were stunted or halted...

...In all fields of endeavor, there is a lapse between the time the light bulb goes on in some investor's head and the time his cash register starts playing its merry tune...

...It is widespread: An estimated 37.8 million Americans have clinically observable signs of it, about 30 million of them the osteotome that attacks the joints...

...To obtain relief from what it regards as onerous interference by bureaucrats, the pharmaceutical industry made a major effort in the Ninety-seventh Congress to win special concessions on patents...

...you can treat it but you can't cure it...

...So who will benefit from this legislation...

...So is the nature of the fund transfer that would result from extension of drug patents...

...sufferers can be counted on as a steady market...

...The report on side-effects was grossly lacking in mention of possible liver involvement...

...The British, meanwhile, had suspended its use after deaths in the United Kingdom had mounted to sixtyone, and the Danes had restricted its use to hospitals, where patients could be carefully monitored...

...Of course, a drug can fetch its own price if it is beneficial (or promoted so doctors and patients think it is) and has no competition...

...Friedman is not the only non-industry supporter of the notion that a drug lag injurious to American public health exists...

...They would not have to show that their product cured anything, just that it wouldn't kill or injure the patient...

...It promised onea-day relief as effective as that obtained from the multiple doses that people on shorter-acting aspirin have to take, with no side-effects worse than "in a mere one per cent of the cases...

...they suspect corners are being cut on both the safety and efficacy provisions that govern the licensing of drugs under the world's strictest code...

...Their need for a special form of relief that other industries will not get is questionable, to say the least...

...At press conferences in New York, Chicago, and Los Angeles, flacks trumpeted the drug as "a new direction in anti-arthritic therapy" that "may also limit the actual joint destruction . . . caused by the progression of the disease...

...Unlike hospital and doctor bills, which are paid for at least in part by Medicare, old people's outpatient drugs are paid for out-of-pocket...

...As a class, they are also poorer and have little prospect of increasing their income beyond cost-of-living adjustment under Social Security, which the Reagan Administration seeks to reduce...

...Aminorex, an appetite suppressant approved in Switzerland, Germany, and Austria, caused twenty-six deaths and additional lasting disabilities before being banned...

...Oraflex, or benaxoprofen, to use its generic name, was on the market in Britain under the brand name Opren for a year and a half before it was approved for use in the United States last April...

...Oraflex may deserve a place in Guinness 's Book of World Records for the drug with the shortest life in interstate commerce...

...If pharmaceutical R&D has been lagging, figures unearthed by the Congressional Office of Technology Assessment certainly do not suggest this...

...FDA statistics show there is plenty of innovation going on in the drug industrybut not very much of it is honest change It was something of an unscheduled embarrassment for the drug-makers when, the day before the patent bill came up for a vote under suspension of the rules, HoffmanLaRoche began marketing a drug called Accutane, heralded as useful against severe cystic acne...

...It was "a documented fact," Shacknai wrote, that the "availability of new drug therapies [had] been delayed, often for years, by bureaucratic intransigence" that contributed nothing to the assurance of a drug's safety...

...It would have squeaked through the House under a technicality called "suspension of the rules" this fall, but for some consciousness-raising by a handful of consumer-oriented members who saw it—in the words of one—as "a massive transfer of funds from the elderly and the sick to one of the most prosperous segments of American industry...

...If a drug manufacturer were to devise a disease for which to develop a profitable medicine, he could hardly improve on arthritis...

...Ian Shedden, a Lilly vice president, told the British Medical Journal in a letter that there were no cases of liver trouble in "over 2,200" carefully monitored patients...

...To attempt to hold it and manufacturers to some higher, impossible standard of knowledge as the price for continued progress would be to send pharmaceutical medicine back to the leechers of the Dark Ages...