-New England Journal of Medicine, October 7, 2004
In this book, her most recent, Marcia Angell explores pharmaceutical research, deplores the rapidly expanding involvement (and distortion of truth) of Big Pharma, and implores us all (physicians, patients, politicians) to do something about it. The dust-jacket blurb asserts that Angell, "during her two decades at [the Journal] had a front-row seat on the growing corruption of the pharmaceutical industry." Perhaps, but since leaving the Journal, she's gone behind the curtains of Big Pharma, Big University, and Big Faculty. Drawing on her own work and on her thoughtful analysis of research, company financial statements, and investigative reports into drug development and marketing, Angell writes with the unambiguous and unyielding style that Journal readers came to expect and trust. By Angell's account, the current slide toward the commercialization and corruption of clinical research coincided with the election of President Ronald Reagan in 1980 and the passage of the Bayh-Dole Act, a new set of laws that permitted and encouraged universities and small businesses to patent discoveries from research sponsored by the National Institutes of Health (NIH). Research paid for by the public to serve the public instantly became a private, and salable, good, one that is producing drug sales of more than $200 billion a year. Commercialization had both specific and broad effects. Readers of this journal and others are familiar with investigations into the control that research sponsors at pharmaceutical companies exert on the design and analysis of clinical trials (including the distortion of primary outcome measures in trials) and the issue of reporting, nonreporting, and biased reporting of results. Angell reminds us of the increasingly cozy relationships between big industry and the faculties of universities. Not only are narcissistic donors renaming the medical schools; they are buying access to the best minds of their faculties. Angell's examples of the large consulting fees paid by industry to individual faculty members and to NIH scientists and directors are astounding. The broader effects are felt in the commercialization of universities, medical faculties, and our profession. In 2000, in a letter written in response to Angell's Journal editorial, "Is Academic Medicine for Sale?" a reader supplied the answer: "No. The current owner is very happy with it." The increasing intrusion of industry into medical education and the almost complete domination of continuing medical education (especially regarding drugs) by the marketing departments of large pharmaceutical companies are a scandal. The same companies also spend heavily to lobby governments. According to Angell, Pharmaceutical Research and Manufacturers of America, the pharmaceutical industry's U.S. trade association, has "the largest lobby in Washington," which in 2002 employed 675 lobbyists (including 26 former members of Congress) at a cost of more than $91 million. The result has been above-average growth in corporate profits during both Republican and Democratic administrations. The most recent and (at least to observers outside the United States) perplexing lobbying effort caused Congress explicitly to prohibit Medicare from using its huge purchasing power to get lower prices for drugs, thus opening up a dollar pipeline, in the form of higher drug prices, directly from taxpayers to corporate coffers. These changes, along with the cave-in by the Food and Drug Administration (FDA) in 1997 that permitted direct-to-consumer advertising to bypass mention in their ads of all but the most serious side effects, have further augmented profits. The overall effect has been a corruption not only of science but also of the dissemination of science. Angell documents that, contrary to what they claim, large pharmaceutical companies have "paltry output" in innovative research. In fact, as permitted by Bayh-Dole, pharmaceutical companies buy discoveries coming out of the basic-science enterprises, including universities and publicly funded granting agencies. The real costs of research on drugs by pharmaceutical companies are much less than the oft-quoted $800 million or so per new drug brought to market. Most of their research is on me-too drugs -- unoriginal, tax-deductible (and thus paid for in lost taxes by the public), and mostly unnecessary, except for corporate profits and executive bonuses. The Big Pharma companies are, in essence, manufacturing and marketing companies. Angell's concluding chapter, the least convincing one in an otherwise fascinating and penetrating book, contains the solutions, all of them predictable (and probably unattainable): control me-too drugs, re-empower the FDA, oversee Big Pharma's clinical research, curb patent length and abuse, keep Big Pharma out of medical education, make company financial statements transparent (so we can tell what the costs of research really are, as distinct from marketing), and impose price controls or guidelines. Granted, the problems are so prevalent and the corporate tentacles so entwined with our way of being that it is hard to see what else to recommend. But perhaps Angell is right. We must change the way we manage research and the development and distribution of new drugs. Not only are health and health care at risk, but so are the research enterprise and the reputations of universities and governments. The integrity of scientific research is too important to be left to the invisible hand of the marketplace. John Hoey, M.D.