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The Truth about the Drug Companies: How They Deceive Us and What to Do about It
By Marcia Angell
Random House, 305 pages, $24.95
On the Take: How Medicine's Complicity with Big Business Can Endanger Your Health
By Jerome Kassirer
Oxford University Press, 251 pages, $28
The two books under review here are often grouped together in the rapidly growing category of anti-pharmaceutical-industry tracts, along with Merrill Goozner’s (2004) The $800 Million Pill: The Truth Behind the Cost of New Drug and Jerry Avorn’s (2004) Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs, among others. Perhaps this pairing is encouraged because both Angell and Kassirer are past editors of the New England Journal of Medicine (Kassirer was first). In a highly favorable review published in Journal of the American Medical Association, Michael Wilkes (2005) treats the two books as largely reinforcing each other, with only trivial differences in viewpoints or policy proposals.
However, this is a misconception of the situation. Angell and Kassirer have written different books that are at odds in fundamental ways. I begin with Angell’s The Truth about the Drug Companies: How They Deceive Us and What to Do about It. This book would satisfy anyone’s definition of an anti-industry polemic, including its vigorous attacks on pharmaceutical marketing in its various forms (of which there are many, as Angell correctly notes). She brings to her task a remarkable background as the long-time managing editor and, then, editor of the New England Journal of Medicine. Angell also possesses formidable skills as a popular writer who can translate difficult material (not all of it purely medical) into highly accessible prose. This was evident in her only other book, Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case (Angell 1996). Science on Trial is an admirable account of how the tort liability system leveraged what proved to be slipshod science of silicone breast implants into product withdrawals, which was followed by a wave of bankruptcies among firms for which the product was no more than a modestly profitable sideline.
Angell devotes considerable attention to pharmaceutical marketing, which she defines broadly to include a multitude of relationships, financial and otherwise, between the industry and the physicians, clinics, and hospitals that are its targets. Some of this material is intriguing precisely because of its breadth. She argues that the usual numbers on the volume of marketing expenditures (mainly measured as media plus physician detailing and the distribution of free samples) are misleading because firms typically report far larger amounts in a catch-all “administration and marketing” account. She suspects that marketing actually accounts for approximately 30% of total revenues rather than the usual figure of 8%-12%. The extra amounts are presumably spent on continuing medical education, speaker and consultant fees, and myriad other activities that in one way or another induce physicians to favor one brand over another and to inform their colleagues about it.
Angell also argues that a lot of research and development (R&D) expenditures could just as easily be classified as marketing. She has a point, though she pushes it too far. What she mainly has in mind are clinical trials designed to accustom doctors to prescribing a drug rather than to add to the science base. Perhaps this is common, though hard data are scarce. However, I find it difficult to believe that this amounts to much compared with the complex trials that cost tens or hundreds of millions of dollars that are launched to meet Food and Drug Administration (FDA) standards for approving new drugs or to persuade either the FDA or the medical community to endorse new indications for old drugs. Nonetheless, that marketing and research overlap is undeniable. What is far more questionable is Angell’s assumption that this is usually a bad thing. Good research can enhance a product’s value, which can then be exploited through explicit marketing or routine dissemination of medical knowledge. A now classic example is the research undertaken by Bristol-Myers Squibb to enhance the competitive advantages of its Pravachol cholesterol-reducing drug in relation to Merck’s Zocor, the first synthetic statin drug. That research was the first to demonstrate persuasively that reducing serum cholesterol would prevent heart attacks (Langreth 1998; Shephard et al. 1995). This marketing-driven result proved extraordinarily valuable in the treatment of coronary heart disease by all statins, not just Pravachol.
Angell dwells at length on the strength and variety of pharmaceutical industry influences on the FDA, academia, government research institutions, and government health care payers. Although these sections are written in a tendentious style, there is nothing wrong with a reminder that pervasive regulation and government funding will eventually entwine private and public parties in what, at times, is a mutually satisfying embrace with scant regard for the welfare of the rest of the world.
Perhaps the most striking aspect of Angell’s book is her intense criticism of the pharmaceutical industry as an engine of R&D. She argues that most breakthrough drugs are actually developed by the National Institutes of Health (NIH) and the academic research it supports. The argument is largely anecdotal, however (for a more authoritative treatment of the main examples, which include erythropoietin, a biotechnology treatment sold as Epogen and Procrit for treating the side effects of cancer chemotherapy and kidney dialysis, respectively, and the cancer drug Gleevec, see Goozner 2004). She does not address why the NIH fails to command huge license fees, instead often needing to search for takers when promising new drugs are ready for expensive clinical testing at great financial risk.
Angell’s most-cited and controversial argument is that most new drugs are little, if any, better than the older ones they compete with and, therefore, waste health care dollars when they rather than generic versions of pioneer drugs are prescribed. Her sweeping claims include such important therapeutic classes as the statin cholesterol-reducing drugs and the selective serotonin reuptake inhibitor (SSRI) antidepressants (beginning with Prozac), for which follow-on drugs using similar biological mechanisms have been successful even after the pioneers lost patent protection and became available as cheap generics. She argues that these “me-too” drugs (to use an increasingly popular pejorative term) are of negligible value. The obvious question is why even the best-trained physicians and most prestigious clinics persist in prescribing newer statins, SSRIs, and so on. Angell’s explanation is to blame clever marketing. However, other factors provide better explanations for the prominence of new drugs in old therapeutic classes. Largely developed parallel to rather than in the wake of pioneer drugs, follow-on drugs are usually priced below predecessor brands and rapidly erode the capital value of pioneering brands by stealing market share (DiMasi and Paquette 2004; Lichtenberg and Philipson 2003). New brands typically do what marketing theory would predict, which is to cater to patients who are poorly served by existing drugs in terms of efficacy and side effects (Lee 2004).
All this seems more like competition than an assault on consumer welfare. In addition, follow-on drug research greatly expands the science base, which otherwise would become stagnant as patents on pioneer brands expire. I mentioned research on statins, but that is far from the only example: SSRIs have evolved into tools for exploring the many potential roles of serotonin reuptake (Holden 2003), and the Cox-2 inhibitors, including Celebrex and Vioxx (before the latter was withdrawn for safety problems that appear to be common to most of the older nonsteroidal anti-inflammatory drugs [Jenkins and Seligman 2005]) are also relevant. Nonsteroidal anti-inflammatory drugs include popular over-the-counter drugs, such as ibuprofen (sold as Advil and other brands) and naproxen (sold as Alleve), and a variety of prescription pain relievers for arthritis and other conditions. They are probably the most widely used of all drugs. However, clinical trials dried up as patents expired, leaving only the Cox-2s as drivers of new research on promising uses, such as cancer prevention (Chau and Cunningham 2002) and, oddly enough in view of the withdrawal of Vioxx because of heart attack risk, prevention of cardiovascular diseases (Hankey and Eikelboom 2003).
Angell suggests change. She would have the FDA require manufacturers to demonstrate that new drugs are superior to existing treatments, not just a placebo. Whether this rule would actually keep me-too drugs off the market is unclear, given that such drugs usually demonstrate superiority for important patient subgroups, but the rule would certainly increase R&D costs. Her other proposals are far more radical: shorter patent lives, a new NIH division to conduct all clinical trials at the manufacturers’ expense, and uniform prices negotiated or set by the federal government and coordinated with foreign governments. Essentially, Angell suggests reliance on a largely government-run, cost-plus pharmaceutical R&D enterprise. Because no such institution exists now, dismantling the current system (which after all has created most of the drugs whose prices are controversial precisely because most physicians believe that the drugs are essential) would be an extraordinary gamble.
The unsuspecting reader might assume that Kassirer’s On The Take: How Medicine’s Complicity with Big Business Can Endanger Your Health is from the same mold as Angell’s book. Indeed, both authors explore many of the same topics, and they vigorously criticize the pharmaceutical industry. However, the two authors have very different things in mind. For example, consider the crucial topic of drug development. Whereas Angell believes that most new drugs are of little value, Kassirer goes out of his way to emphasize the value of the most widely used newer drugs, including that of the SSRI antidepressants (p. 125), a category Angell singled out for criticism.
Kassirer’s account parallels much of Angell’s critical survey of the pharmaceutical industry’s pervasive influence over physicians and academia, albeit in a more entertaining manner that draws on numerous personal and second-hand anecdotes. However, again, there are essential differences between the two. If industry influence wreaks harm, where is the locus of blame? For Angell, it is the industry itself. For Kassirer, a different answer is embodied in his book’s subtitle: “… Medicine’s Complicity with Big Business....” Kassirer focuses (correctly, in my view) on the recipients of industry funds, including physicians, professional organizations (especially these organizations), hospitals and clinics, and academic institutions. He also names names, including some prominent academics. As does Angell, Kassirer views industry marketing as a huge enterprise comprehensive of essentially all funding save essential clinical trials, and he believes that marketing is the source of numerous and profound problems. However, his fascinating and occasionally alarming details are mostly about what the recipients do, not what the drug firms do, whereas Angell emphasizes the givers (i.e., the industry).
Kassirer’s core message is that physicians today cater too much to interests other than those of their patients and do so to a far greater extent than they did when he was a young doctor a half century or so ago. Why did this happen? Kassirer’s extended and discursive analysis is full of insights, even when he is most dyspeptic. He makes clear that the deepest problems and conundrums arise from two sources: Ironically, the first factor is the arrival of effective drugs (see the discussion of Prozac on p. 125), the use of which has given physicians powers they previously lacked, and the second factor, on which he spends much of his time, is the growth of third-party payments for health care in general and pharmaceuticals in particular.
Kassirer correctly views health insurance as “perhaps the most powerful influence” (p. 174) that has increased conflicts of interest in physician-patient relationships. The essential new element is that “doctors and facilities that could provide such services [covered by insurance or Medicare] were more or less assured of payment” (p. 175). He gives special attention to Medicare, which he believes “drove much of the charitable ethos out of medicine” (p. 175). An example of Medicare’s profound influence is how reimbursement for kidney dialysis changed the specialty of nephrology (kidney ailments) (see p. 214). Another example lies in Medicare reimbursement for in-office cancer chemotherapy; as with nephrology, the peculiar details of the Medicare system simultaneously increased physician incomes while distorting treatment incentives. It is not only specialists who are affected. Kassirer notes (p. 174) that physician incomes, compared with those of the general population, increased dramatically in the three decades after Medicare began in 1965. He gives far less attention to Medicaid, the up-and-coming entitlement whose total costs have eclipsed Medicare since Kassirer began writing his book.
Kassirer avoids falling into the trap of thinking that physician incentives would be cured by removing pharmaceutical marketing and third-party reimbursement, including health insurance and government programs. Many excellent passages delineate the conflicts of interest inherent in all known financial arrangements, beginning with old-fashioned, first-party, fee-for-service payment (pp. 132-34) and proceeding through third-party, fee-for-service payment (the original model for private insurance and Medicare before their costs expanded beyond reason), managed care with and without capitation (fixed annual fees per patient), and so on. “Every method of physician payment creates a financial conflict of interest for the doctor” (p. 134). Kassirer illustrates this point nicely with quotations ranging from Boston Medical and Surgical Journal (the New England Journal’s predecessor) in 1847 to Eugene O’Neill’s Long Day’s Journey in Night: “[Doctors] are all alike. Anything, they don’t care what, to keep you coming to them” (pp. 171-72). Thus, Kassirer parts ways with critics of modern health care who believe that physicians in the 1960s and earlier had no trouble internalizing their patients’ preferences despite obvious conflicts of interest.
Kassirer believes that norms and attitudes are the most important influences of all. In his final analysis (p. 189), he puts the onus squarely on his fellow practitioners and academics for sacrificing their patients’ trust by failing to resist the excesses of managed care and by accepting “pseudo-consulting,” clinical trial bonuses and other rewards from the pharmaceutical industry. However, Kassirer cannot solve the central conundrum, namely, how to separate active bias (i.e., actual behavior against a patient’s interest) from mere conflicts of interest, whether in appearance or in fact, which may never generate untoward behavior. The conundrum is not his alone, which is why ethical codes and even regulations and legislation routinely proscribe conflicts of interest without regard to whether such conflicts give rise to adverse behavior. In this case, the problem is essentially economic. For example, suppose that conflicts of interest were abolished by severely limiting firms from providing research funding, continuing medical education support, or even disseminating at low cost (to physicians) useful new medical information that would otherwise fail to be disseminated quickly or widely. The difficulty is that few parties other than pharmaceutical firms have strong incentives to undertake the considerable costs of making accessible many of the latest practice guidelines, consensus reports, treatment studies, and clinical trial results. Indeed, Kassirer’s book is rather good at describing the financial vacuums that pharmaceutical firms fill, especially for continuing education; the essential reality is that physicians would rather attend industry-supported seminars than cover the seminar costs themselves.
Kassirer makes clear that the forces that beset the profession he loves arise from many sources in addition to the drug industry. That his book is often perceived as being mainly about the influence of the pharmaceutical industry is hardly accidental, however. A back-cover blurb by Massachusetts Senator Edward Kennedy notes, “Dr. Kassirer has written an important and thought-provoking analysis of the extensive conflicts of interest that pervade the relationship between pharmaceutical companies and the medical profession.” Kassirer’s own summary (p. 187) provides a more complete list of the reasons “many of America’s doctors pay more attention to their own desires than to the health of their patients: [He] propose[s] that the runaway cost of care, changing financial incentives, inflated income expectations, falling physicians’ income, changes in patent law, and substantial influence of industry on medical research were essential ingredients.” He then adds to his list by citing changes in societal attitudes about which financial entanglements are acceptable.
As does Angell, Kassirer proposes changes, though he has far less confidence that his plans will work. He begins with “principles” (mainly for physicians and professional organizations), moves through transparency (which can be counterproductive) and other private measures, and concludes with regulation. However, none of these measures provides solutions. There are too many gray areas, too many situations in which identical conditions generate different behavior depending on who is involved, and especially the possibility that even well-intentioned plans will do more harm than good. For example, some universities are more thorough than others in policing conflicts, but it is not obvious which universities do this correctly or even that there is any right way to do it: “There is no simple way to preserve the entrepreneurial spirit that has created [magnetic resonance imaging] scans, stents, bioengineered drugs, and artificial knees and at the same time completely eliminate financial conflicts of interest” (p. 202). In the end, it all comes back to physicians themselves: “Even with rigorous guidelines, pharmaceutical companies will seek ways to influence physicians, especially prominent academics and community ‘thought leaders.’ Doctors must take personal responsibility for their behavior” (pp. 207-208). However, Kassirer provides little reason to believe that this will happen. In the end, his passionate book is a diagnosis without a reliable cure.
John E. Calfee is a resident scholar at AEI.
References
Angell, Marcia (1996), Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case. New York: W.W. Norton & Co.
Avorn, Jerry (2004), Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs. New York: Knopf.
Chau, Ian and David Cunningham (2002), “Cyclooxygenase Inhibition in Cancer: A Blind Alley or a New Therapeutic Reality?” New England Journal of Medicine, 346 (14), 1085-1087.
DiMasi, Joseph A. and Cherie Paquette (2004), “The Economics of Follow-On Drug Research and Development: Trends in Entry Rates and Timing of Development,” Pharmacoeconomics, 22 (2), 1-14.
Goozner, Merrill (2004), The $800 Million Pill: The Truth Behind the Cost of New Drugs. Berkeley: University of California Press.
Hankey, Graeme J. and John W. Eikelboom (2003), “Cyclooxygenase-2 Inhibitors: Are They Really Atherothrombotic, and If Not, Why Not?” Stroke, 34 (November), 2736-40.
Holden, Constance (2003), “Future Brightening for Depression Treatments,” Science, (October 31), 810-13.
Jenkins, John K. and Paul J. Seligman (2005), “Analysis and Recommendations for Agency Action Regarding Non-Steroidal Anti-Inflammatory Drugs and Cardiovascular Risk,” FDA memorandum, Center for Drug Evaluation and Research, Office of New Drugs, (April 6), (accessed May 1, 2005), [available at http://www.fda.gov/cder/drug/infopage/COX2/NSAIDdecisionMemo.pdf].
Langreth, Robert (1998), “Drug Marketing Drives Many Clinical Trials,” Wall Street Journal, (November 16).
Lee, Thomas H. (2004), “Perspective: ‘Me-Too’ Products: Friend or Foe?” New England Journal of Medicine, 350 (3), 211-12.
Lichtenberg, Frank R. and Tomas J. Philipson (2003), “The Dual Effects of Intellectual Property Regulations: Within- and Between-Patent Competition in the U.S. Pharmaceuticals Industry,” Journal of Law and Economics, 45 (October), 643-72.
Shephard, James, Stuart M. Cobbe, Ian Ford, Christopher G. Isles, A. Ross Lorimer, Peter W. Macfarlane, James H. McKillop, and Christopher J. Packard, for the West of Scotland Coronary Prevention Study Group (1995), “Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia,” New England Journal of Medicine, 333 (20), 1301-1307.
Wilkes, Michael (2005), “Review of Angell’s The Truth About the Drug Companies: How They Deceive Us and What to Do About It, and Kassirer’s On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health,” Journal of the American Medical Association, 293 (24), 3107-3108.
