Does Pharma Need a New Prescription?

THE TRUTH ABOUT THE DRUG COMPANIES: How They Deceive Us and What To Do About It, by Marcia Angell, Random House, 2004, 336 pages, $24.95 (ISBN 0-375-50846-5)

CON: ANGELL'S BOOK FAILS TO CONVINCE
REVIEWED BY JOHN E. CALFEE

Marcia Angell, a medical doctor, was for some two decades an editor of the New England Journal of Medicine, serving as managing editor for about half that time. In 1995, she published "Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case," a forceful critique of the liability system. Her new book joins a growing list of fiercely critical assessments of the pharmaceutical industry, including such substantial works as Merrill Goozner's "The $800 Million Pill: The Truth Behind the Cost of New Drugs" and Jerry Avorn's "Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs."

Angell is a good writer, and her book is a quick and easy read for a popular audience, despite the difficulty of many of its topics. In her critical appraisal of one of her favorite targets, marketing, Angell provides a useful reminder that the line between marketing and R&D can be a fuzzy one, or rather, that a single activity can serve both goals. This is not necessarily a bad thing, because valuable research can be performed with marketing goals in mind. The clinical trials undertaken by Bristol-Myers Squibb to bolster its Pravachol statin drug, for example, provided the first persuasive demonstration that reducing serum cholesterol would prevent heart attacks.

Still, there's nothing wrong with pointing out, as Angell does, that what looks like R&D can sometimes be undertaken mainly to solidify relationships with prescribing physicians rather than to advance pharmaceutical science. She provides no evidence, however, that this kind of thing accounts for a significant proportion of the many billions of dollars spent annually on R&D.

Angell spends several chapters describing industry influences on the Food & Drug Administration, physicians, academic research institutions, and government health care payers. Her analysis is a useful reminder of the powerful relationships that grow in parallel with the rise of regulation and government financing of health care. One may also argue about cause and effect--Is the continuing medical education establishment a victim of industry funding or is it a supplicant?--but the details she presents are very much worth understanding.

Despite these and other instances of information and insight, much of this book is disappointing. It is oddly unscholarly, given its provenance. The endnotes reveal a surprisingly high proportion of sources from the popular press, probably well over half, frequently supplemented by work from a small circle of nonprofit organizations with a decidedly anti-industry orientation, such as Public Citizen. Even in what should be rather technical discussions, such as the sections on research and the value of new drugs, many crucial points are supported by items from the Wall Street Journal or nonscholarly reports from think tanks.

Angell's claim that direct-to-consumer advertising of prescription drugs is a powerful driver of inappropriate usage relies upon two reports by a single set of authors, ignoring a substantial body of research documenting substantial benefits and little, if any, harm from these ads. Her assessment of the most prominent peer-reviewed study of the costs of developing a new drug, from Tufts Center for the Study of Drug Development in 2003, cuts that estimate in half simply by dispensing with the economic concept of opportunity cost (the gains from investment funds that are tied up during R&D). Angell is correct, however, in noting that the entire question of research costs is difficult to address in a fully satisfying manner, given the scarcity of publicly available data sources.

Angell also claims that the most innovative and useful drugs are discovered through federally funded research, and that many of them are essentially given away to the private sector. She focuses on just a few examples--Taxol, Epogen, and Gleevec--which are already familiar from other popular accounts. She does not address the crucial question of why the National Institutes of Health has generally had trouble finding licensees for the many candidate drugs coming out of its funded work. It's hard to reject the hypothesis that instead of being certain successes, the drugs emerging from NIH laboratories typically face highly uncertain prospects in the arduous path toward FDA approval.

Central to Angell's book is her assessment of the value of new drugs, especially the so-called me-too or follow-on drugs that compete with the pioneer brand in a therapeutic category. Angell claims that most of these drugs provide negligible value, increase health care costs, and divert R&D resources from more useful innovations. To her credit, Angell provides a list of the me-too drugs she thinks we don't need. It includes the popular statin class of cholesterol drugs, including Lipitor, Zocor, and Pravastatin, that compete with generic Mevacor, and the post-Prozac selective serotonin reuptake inhibitor (SSRI) class of antidepressants, such as Zoloft and Paxil.

Angell's analysis is open to criticism on several grounds. Modern follow-on drugs are developed in parallel rather than in the wake of pioneers, are usually priced below predecessor brands, and rapidly erode the capital value of pioneering brands. They typically cater to patients poorly served by existing drugs. An initially narrow therapeutic class may open the path to a variety of therapeutic approaches, as SSRIs have evolved into tools for exploring the role of serotonin reuptake. Finally, follow-on drug research greatly expands the science base, with statins a previously mentioned example.

Angell describes a bleak future for an industry beset by importation from nations with price controls, a stalled new-drug pipeline, resurgent litigation, and state-level restrictions and price controls. She proposes radical measures to save the industry, which she thinks is very much worth saving. Manufacturers would have to demonstrate that new drugs are superior to existing treatments, not just a placebo. Although this would increase R&D costs dramatically, it may not keep me-too drugs off the market if they demonstrate superiority for important patient subgroups.

Angell also advocates much shorter patent lives, a new NIH division to run all clinical trials at the manufacturers' expense, and uniform prices negotiated or set by the federal government and coordinated with foreign governments. These measures represent a bold gamble that a largely government-run, cost-plus R&D enterprise would generate the pharmaceutical advances that Angell wants while avoiding the waste she deplores.

John E. Calfee, an economist, is a resident scholar at the American Enterprise Institute in Washington, D.C. He has consulted for a number of pharmaceutical firms, and some of his research has been partially funded by the pharmaceutical industry. His employer receives financial contributions from individuals, foundations, and corporations, including pharmaceutical firms.

PRO: DRUG COMPANIES CAN BEHAVE LIKE BULLYING BEASTS
REVIEWED BY ALAN CASSELS

It's an octopus.

At least for a former Canadian Navy scuba diver like myself who once wrestled with one, that's the first metaphor that comes to mind. The main "truth" about the pharmaceutical industry unveiled in Marcia Angell's book is that it is a multilimbed beast capable of being everywhere and into everything at once. And her prescription is that society needs to keep that creature at arm's length to avoid further imperiling our health.

With a refreshing editorial zeal, buttressed by substantial references, Angell's book describes the tentacles of the pharmaceutical industry as massively influential, resilient, and resourceful to a truly breathtaking degree. It skillfully maneuvers on multiple fronts, driven by a focused singularity of purpose. For most readers new to this topic, the insidious behavior she describes of this, the most profitable (and some say most regulated) private enterprise in the history of our planet, will shock, astonish, and anger.

The pharmaceutical industry as a servant of medicine is capable of much good in extending life and relieving suffering. But it has become crudely, some would say fatally, entangled with commerce. Angell describes how this octopus bullies and infiltrates the drug regulatory system, deceives doctors with lavish gifts, deploys scandalous marketing budgets, underwrites the very "creation" of disease, and works relentlessly to shape the perceptions of consumers who ultimately swallow its products.

Her description of the astonishingly close hold that the pharmaceutical industry has on elected legislators (for example, employing more than one lobbyist for each member of Congress), and its ability to shape regulatory ground rules to its advantage, is chilling. Equally disturbing is the degree to which society has permitted drug companies to run largely unfettered, letting them control research and mislead doctors, all the while extorting health budgets and justifying that extortion with their alleged contributions to society.

While some may criticize Angell, a medical doctor, for delivering more of an extended diatribe than hard journalism, she's no crank. A former editor of the New England Journal of Medicine, one of the top five medical journals in the world, her opinions have an authority stemming from viewing medicine from within the establishment--from the pinnacle of the orthodoxy.

Richard Horton, editor of the Lancet, has criticized Angell for not presenting the side of chief executives and medical directors of the pharmaceutical industry. He is being naive. Angell's argument is simply too well supported to be dismissed or altered by any number of weaselly explanations from pharmaceutical company CEOs.

Criticism of the pharmaceutical industry illustrates a curious phenomenon itself. When anyone tries to pry off one tentacle, many others rise up to defend the beast. Recently, in Barcelona, members of the pharmaceutical industry's global lobby group, the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), met to discuss what to do about recent bad press and withering attacks in an industry trade publication.

Angell's solution would be to reform the "Enronesque" practices that the public and doctors find most reprehensible. But the lobbyists are more interested in planning offensive operations, at meetings urging the drug industry to make its public battle a top priority. I am sure Angell has promoted herself to "enemy number one" with her book.

Granted, these are hard times for big pharma. Last year witnessed some extraordinary sights, such as a Food & Drug Administration drug safety expert testifying before a Senate committee that FDA was "virtually incapable of protecting America" from unsafe drugs; the withdrawal of Vioxx, one of the most advertised and prescribed drugs in the world; and a series of lawsuits against drug giant GlaxoSmithKline for concealing important data on the effects of antidepressants on children. Decades from now we may look back at 2004 as epochal, in the same light as the thalidomide disaster in the 1960s, which ushered in important safety regimes the world over.

A series of new books promises to make pharmaceutical companies uneasy. Leading the pack are "Medicines Out of Control? Antidepressants and the Conspiracy of Goodwill" by Charles Medawar and Anita Hardon, and Jerry Avorn's hefty tome, "Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs."

Merrill Goozner's "The $800 Million Pill: The Truth Behind the Cost of New Drugs" and Katharine Greider's "The Big Fix: How the Pharmaceutical Industry Rips Off American Consumers," like Angell's book, zero in on the drug industry's rhetoric about the costs of developing new drugs.

And Jerome P. Kassirer's "On the Take: How Medicine's Complicity with Big Business Can Endanger Your Health" focuses primarily on how financial conflicts of interest, what he calls "the culture of greed," infiltrate and disgrace the medical profession.

Angell displays uncommon energy and valor by diving into the waters where the pharmaceutical octopus lurks, and in the subtitle of the book, "How They Deceive Us and What To Do About It," she invites us to begin the serious global discussion of how to disentangle--to unwind ourselves and our institutions from the tentacles of this industry.

As a naval lieutenant, Alan Cassels spent 12 years in the Canadian Navy navigating ships and scuba diving. He has since gained a decade of experience researching prescription drug policy and is coauthor with Ray Moynihan of the forthcoming book, "Selling Sickness: How the Drug Companies Are Turning Us All into Patients." He is currently a drug policy researcher at the University of Victoria, in British Columbia.