Pharmageddon. David Healy

when members of his staff found that several versions of the same antibiotic, marketed by different companies, had identical prices, and that the prices being charged were of the order of a 1000 percent of the price of manufacture. As they explored the issues, Kefauver's staff found compelling evidence that companies were secretly engaging in cartel practices to maintain the price of medicines and corrupting doctors with backdoor payments to prescribe on-patent and more expensive drugs. There seemed to be, as Kefauver put it, “an upside down competition where prices continue to go up even when production remains low or declines.”⁴³ As the chair of the Senate antitrust and monopoly subcommittee he had the mandate to investigate what might be behind the apparent price-rigging.

      Another concern of Kefauver's was the advertising for drugs. There was the sheer volume. As Walter Griffith of Parke Davis told Kefauver, “the ethical pharmaceutical industry of this country” had turned out “3,790,908,000 pages of paid journal advertising” and “741,213,700 direct mail impressions.”⁴⁴ But of greater concern was that the ads were commonly misleading and in many cases downright fallacious. Kefauver's staff unearthed one ad for an antibiotic which displayed two chest X-rays, giving the impression of clinical improvement when the X-rays in fact came from two different patients neither of whom had had the antibiotic featured. As Dale Console, a former medical director at the Squibb pharmaceutical company later put it at Kefauver's Senate hearings, “If an automobile does not have a motor, no amount of advertising can make it appear to have one. On the other hand, with a little luck, proper timing, and a good promotion program, a bag of asafetida with a unique chemical side chain can be made to look like a wonder drug.”⁴⁵

      Yet other concerns lay in drug company practices of withholding safety data on drugs, their lack of testing of new drugs on animals prior to marketing to humans and, more problematically, the fact that the regulators had no procedures in place to ensure a drug worked. The 1938 Food, Drugs and Cosmetics Act solely required companies to demonstrate safety in a number of patients without even basic toxicology testing in animals. As Kefauver's staff noted, if a drug didn't work for a condition for which it was marketed or worked less well than an already available product, then it was inherently unsafe. These discontents led in 1959 to the establishment of the Kefauver-Harris Senate hearings on pharmaceutical practices.⁴⁶

      Kefauver's main target was the patent system, which he thought was primarily responsible for the artificially high prices American patients uniquely faced. At the hearings, he elicited some revealing testimony from Frederick Meyers, a University of California professor of pharmacology who admitted that “most of the program [in drug research] has come from European and British researchers.” The purpose of much of the work done by American drug firms was, according to Meyers, “partly to exploit and market” these foreign products but “mostly to modify the original drug just enough to get a patentable derivative.”⁴⁷ Was this a good idea? Kefauver's staff produced figures to show that out of 77 countries surveyed, 28 allowed product patents and in these countries the prices of drugs ranged from 18 to 255 times higher than in the nonpatent countries, with both American-made and European- made drugs costing far less in Europe than in the United States.

      But as Kefauver found, “These drug fellows pay for a lobby that makes the steel boys look like popcorn vendors…anyone who dares seek the truth will be accused of being a persecutor.”⁴⁸ Up for reelection in 1960, he found himself branded a “socialist hell-bent on ruining healthcare.” He was reelected comfortably, but when it came to his bill, despite having been the 1956 Democratic vice-presidential candidate, Kefauver had no support from the Kennedy administration, who were at the time trying to get Medicaid through Congress and did not want to antagonize the pharmaceutical industry. He also had no support from the American Medical Association, even for something as basic as a requirement that companies prove their drugs work before they are let on the market. The AMA was gearing up to fight Medicaid and was dependent on the increasing revenue it was receiving from pharmaceutical companies advertising in its journals.

      Kefauver's bill (S. 1552) was rewritten by his congressional opponents to make it more company friendly and in this form it seemed to have good prospects of passage. But then reports began to surface from Germany of the effects of a drug called thalidomide. Thalidomide was a sleeping pill sold over the counter in Germany and about to be marketed in the United States by Merrell Pharmaceuticals, when it was linked to a new and disturbing problem—babies of mothers who had taken the drug were born limbless or with useless flippers (phocomelia) where limbs should have been. The makers, Chemie-Grunenthal, fought the linkage to their drug and only removed thalidomide from the German market under pressure. Almost a year after the first reports, Merrell were mailing samples of the compound to American doctors, even though it had still not been licensed in the United States.

      These events transformed the political imperative. Kefauver's bill was resurrected and rushed through both House and Senate, resulting in the 1962 amendments to the Food and Drugs Act. This mandated proper animal testing of drugs for toxicity before launch, and gave the FDA control over advertising. The new bill contained three further provisions whose far-reaching ramifications will be explored in chapters 2 and 3— it maintained prescription-only status for all new drugs, it required that companies demonstrate their drugs worked for a specified condition (where before they only had to prove safety), and it required companies to use controlled studies to demonstrate drug benefits. Kefauver's bill, however, was stripped of its provisions to change patent law, despite support from the Chief Patent Officer. And because the patent law wasn't changed, the 1962 amendments had no effect on Kefauver's primary target—control of the prices of drugs.

      While it failed in its primary objective, the stripped-down bill was passed to wide acclaim. Kefauver, flanked by the junior senator from

      Tennessee, Albert Gore, Sr., had been given the honor of speaking to it on the Senate floor. The disturbing changes in the climate of medicine would be stopped or even reversed, he hoped. Kennedy and Kefauver basked in the glow of success. Frances Kelsey, a staffer at the FDA, whose bureaucratic delay in reviewing and handling the license application for thalidomide undoubtedly restricted the number of American children exposed to the drug in utero, received a President's Award for Distinguished Federal Civilian Service. The reforms to the FDA were copied by other regulatory agencies worldwide. When it came to drugs, the management of pregnancy became the one area of medicine that most closely conformed to Pinel's hopes for all of medicine—that doctors in knowing when not to prescribe would demonstrate the highest medical art. Many still think this to be the case, but today's reality is quite different.

      2

       Medicine and the Marketers

      When she became pregnant in 2004, 38-year-old Gina Fromm did a range of things that few women would have done in the early 1960s— she took cold rather than hot showers in case she might harm her baby, stopped eating yogurt and incinerated chicken because of the risk of bacterial infection, from listeria to salmonella. She balked at taking prenatal vitamins, though she had been taking Paxil following a fleeting episode of anxiety. She continued to take it through her pregnancy; she had found stopping difficult and her doctor reassured her it posed no risk to her baby. On February 2, 2005, her son was born with congenital heart defects.¹

      In the decades following the passage of Senator Kefauver’s bill, women were far less likely to smoke, drink alcohol or coffee, or take painkillers while pregnant. Nevertheless, Paxil and other SSRI antidepressants, among the direct successors of thalidomide, were on their way to becoming the most commonly prescribed drugs in pregnancy— especially in the United States. In 2006, forty-four years after the 1962 amendments to the Food and Drugs Act, the first legal actions were filed for birth defects induced by SSRI antidepressants, resulting in verdicts against GlaxoSmithKline and huge settlements, but this made little dent on the prescribing of SSRIs in pregnancy, which continued to mount.

      Nothing about the 1962 amendments obviously predicted the replays of drug-induced birth defects we now have. Medications continued to be available on a prescription-only basis. With the 1962 amendments to the Food and Drugs Act, companies were to be restricted to selling medications for real diseases rather than for trivial indications like halitosis or fleeting anxiety states. Furthermore, from 1962