Docs drugs and corruption

[Guest guest]

Drug Companies & Doctors: A Story of Corruption By Marcia Angell

Side Effects: A Prosecutor, a Whistleblower, and a Bestselling

Antidepressant on Trial by Alison Bass

Algonquin Books of Chapel Hill, 260 pp., $24.95

Our Daily Meds: How the Pharmaceutical Companies Transformed

Themselves into Slick Marketing Machines and Hooked the Nation on

Prescription Drugs by Melody sen

Crichton/Farrar, Straus and Giroux, 432 pp., $26.00

Shyness: How Normal Behavior Became a Sickness by Lane

Yale University Press, 263 pp., $27.50; $18.00 (paper)

Recently Senator Grassley, ranking Republican on the Senate

Finance Committee, has been looking into financial ties between the

pharmaceutical industry and the academic physicians who largely

determine the market value of prescription drugs. He hasn't had to

look very hard.

Take the case of Dr. ph L. Biederman, professor of psychiatry at

Harvard Medical School and chief of pediatric psychopharmacology at

Harvard's Massachusetts General Hospital. Thanks largely to him,

children as young as two years old are now being diagnosed with

bipolar disorder and treated with a cocktail of powerful drugs, many

of which were not approved by the Food and Drug Administration (FDA)

for that purpose and none of which were approved for children below

ten years of age.

Legally, physicians may use drugs that have already been approved for

a particular purpose for any other purpose they choose, but such use

should be based on good published scientific evidence. That seems not

to be the case here. Biederman's own studies of the drugs he advocates

to treat childhood bipolar disorder were, as The New York Times

summarized the opinions of its expert sources, " so small and loosely

designed that they were largely inconclusive. " [1]

In June, Senator Grassley revealed that drug companies, including

those that make drugs he advocates for childhood bipolar disorder, had

paid Biederman $1.6 million in consulting and speaking fees between

2000 and 2007. Two of his colleagues received similar amounts. After

the revelation, the president of the Massachusetts General Hospital

and the chairman of its physician organization sent a letter to the

hospital's physicians expressing not shock over the enormity of the

conflicts of interest, but sympathy for the beneficiaries: " We know

this is an incredibly painful time for these doctors and their

families, and our hearts go out to them. "

Or consider Dr. Alan F. Schatzberg, chair of Stanford's psychiatry

department and president-elect of the American Psychiatric

Association. Senator Grassley found that Schatzberg controlled more

than $6 million worth of stock in Corcept Therapeutics, a company he

cofounded that is testing mifepristone—the abortion drug otherwise

known as RU-486—as a treatment for psychotic depression. At the same

time, Schatzberg was the principal investigator on a National

Institute of Mental Health grant that included research on

mifepristone for this use and he was coauthor of three papers on the

subject. In a statement released in late June, Stanford professed to

see nothing amiss in this arrangement, although a month later, the

university's counsel announced that it was temporarily replacing

Schatzberg as principal investigator " to eliminate any misunderstanding. "

Perhaps the most egregious case exposed so far by Senator Grassley is

that of Dr. B. Nemeroff, chair of Emory University's

department of psychiatry and, along with Schatzberg, coeditor of the

influential Textbook of Psychopharmacology.[2] Nemeroff was the

principal investigator on a five-year $3.95 million National Institute

of Mental Health grant—of which $1.35 million went to Emory for

overhead—to study several drugs made by GlaxoKline. To comply

with university and government regulations, he was required to

disclose to Emory income from GlaxoKline, and Emory was required

to report amounts over $10,000 per year to the National Institutes of

Health, along with assurances that the conflict of interest would be

managed or eliminated.

But according to Senator Grassley, who compared Emory's records with

those from the company, Nemeroff failed to disclose approximately

$500,000 he received from GlaxoKline for giving dozens of talks

promoting the company's drugs. In June 2004, a year into the grant,

Emory conducted its own investigation of Nemeroff's activities, and

found multiple violations of its policies. Nemeroff responded by

assuring Emory in a memorandum, " In view of the NIMH/Emory/GSK grant,

I shall limit my consulting to GSK to under $10,000/year and I have

informed GSK of this policy. " Yet that same year, he received $171,031

from the company, while he reported to Emory just $9,999—a dollar shy

of the $10,000 threshold for reporting to the National Institutes of

Health.

Emory benefited from Nemeroff's grants and other activities, and that

raises the question of whether its lax oversight was influenced by its

own conflicts of interest. As reported by Gardiner in TheNew

York Times,[3] Nemeroff himself had pointed out his value to Emory in

a 2000 letter to the dean of the medical school, in which he justified

his membership on a dozen corporate advisory boards by saying:

Surely you remember that -Kline Beecham Pharmaceuticals

donated an endowed chair to the department and there is some

reasonable likelihood that Janssen Pharmaceuticals will do so as well.

In addition, Wyeth-Ayerst Pharmaceuticals has funded a Research Career

Development Award program in the department, and I have asked both

AstraZeneca Pharmaceuticals and Bristol-Meyers [sic] Squibb to do the

same. Part of the rationale for their funding our faculty in such a

manner would be my service on these boards.

Because these psychiatrists were singled out by Senator Grassley, they

received a great deal of attention in the press, but similar conflicts

of interest pervade medicine. (The senator is now turning his

attention to cardiologists.) Indeed, most doctors take money or gifts

from drug companies in one way or another. Many are paid consultants,

speakers at company-sponsored meetings, ghost-authors of papers

written by drug companies or their agents,[4] and ostensible

" researchers " whose contribution often consists merely of putting

their patients on a drug and transmitting some token information to

the company. Still more doctors are recipients of free meals and other

out-and-out gifts. In addition, drug companies subsidize most meetings

of professional organizations and most of the continuing medical

education needed by doctors to maintain their state licenses.

No one knows the total amount provided by drug companies to

physicians, but I estimate from the annual reports of the top nine US

drug companies that it comes to tens of billions of dollars a year. By

such means, the pharmaceutical industry has gained enormous control

over how doctors evaluate and use its own products. Its extensive ties

to physicians, particularly senior faculty at prestigious medical

schools, affect the results of research, the way medicine is

practiced, and even the definition of what constitutes a disease.

Consider the clinical trials by which drugs are tested in human

subjects.[5] Before a new drug can enter the market, its manufacturer

must sponsor clinical trials to show the Food and Drug Administration

that the drug is safe and effective, usually as compared with a

placebo or dummy pill. The results of all the trials (there may be

many) are submitted to the FDA, and if one or two trials are

positive—that is, they show effectiveness without serious risk—the

drug is usually approved, even if all the other trials are negative.

Drugs are approved only for a specified use—for example, to treat lung

cancer—and it is illegal for companies to promote them for any other use.

But physicians may prescribe approved drugs " off label " —i.e., without

regard to the specified use—and perhaps as many as half of all

prescriptions are written for off-label purposes. After drugs are on

the market, companies continue to sponsor clinical trials, sometimes

to get FDA approval for additional uses, sometimes to demonstrate an

advantage over competitors, and often just as an excuse to get

physicians to prescribe such drugs for patients. (Such trials are

aptly called " seeding " studies.)

Since drug companies don't have direct access to human subjects, they

need to outsource their clinical trials to medical schools, where

researchers use patients from teaching hospitals and clinics, or to

private research companies (CROs), which organize office-based

physicians to enroll their patients. Although CROs are usually faster,

sponsors often prefer using medical schools, in part because the

research is taken more seriously, but mainly because it gives them

access to highly influential faculty physicians—referred to by the

industry as " thought-leaders " or " key opinion leaders " (KOLs). These

are the people who write textbooks and medical journal papers, issue

practice guidelines (treatment recommendations), sit on FDA and other

governmental advisory panels, head professional societies, and speak

at the innumerable meetings and dinners that take place every year to

teach clinicians about prescription drugs. Having KOLs like Dr.

Biederman on the payroll is worth every penny spent.

A few decades ago, medical schools did not have extensive financial

dealings with industry, and faculty investigators who carried out

industry-sponsored research generally did not have other ties to their

sponsors. But schools now have their own manifold deals with industry

and are hardly in a moral position to object to their faculty behaving

in the same way. A recent survey found that about two thirds of

academic medical centers hold equity interest in companies that

sponsor research within the same institution.[6] A study of medical

school department chairs found that two thirds received departmental

income from drug companies and three fifths received personal

income.[7] In the 1980s medical schools began to issue guidelines

governing faculty conflicts of interest but they are highly variable,

generally quite permissive, and loosely enforced.

Because drug companies insist as a condition of providing funding that

they be intimately involved in all aspects of the research they

sponsor, they can easily introduce bias in order to make their drugs

look better and safer than they are. Before the 1980s, they generally

gave faculty investigators total responsibility for the conduct of the

work, but now company employees or their agents often design the

studies, perform the analysis, write the papers, and decide whether

and in what form to publish the results. Sometimes the medical faculty

who serve as investigators are little more than hired hands, supplying

patients and collecting data according to instructions from the company.

In view of this control and the conflicts of interest that permeate

the enterprise, it is not surprising that industry-sponsored trials

published in medical journals consistently favor sponsors'

drugs—largely because negative results are not published, positive

results are repeatedly published in slightly different forms, and a

positive spin is put on even negative results. A review of

seventy-four clinical trials of antidepressants, for example, found

that thirty-seven of thirty-eight positive studies were published.[8]

But of the thirty-six negative studies, thirty-three were either not

published or published in a form that conveyed a positive outcome. It

is not unusual for a published paper to shift the focus from the

drug's intended effect to a secondary effect that seems more favorable.

The suppression of unfavorable research is the subject of Alison

Bass's engrossing book, Side Effects: A Prosecutor, a Whistleblower,

and a Bestselling Antidepressant on Trial. This is the story of how

the British drug giant GlaxoKline buried evidence that its

top-selling antidepressant, Paxil, was ineffective and possibly

harmful to children and adolescents. Bass, formerly a reporter for the

Boston Globe, describes the involvement of three people—a skeptical

academic psychiatrist, a morally outraged assistant administrator in

Brown University's department of psychiatry (whose chairman received

in 1998 over $500,000 in consulting fees from drug companies,

including GlaxoKline), and an indefatigable New York assistant

attorney general. They took on GlaxoKline and part of the

psychiatry establishment and eventually prevailed against the odds.

The book follows the individual struggles of these three people over

many years, culminating with GlaxoKline finally agreeing in 2004

to settle charges of consumer fraud for $2.5 million (a tiny fraction

of the more than $2.7 billion in yearly Paxil sales about that time).

It also promised to release summaries of all clinical trials completed

after December 27, 2000. Of much greater significance was the

attention called to the deliberate, systematic practice of suppressing

unfavorable research results, which would never have been revealed

without the legal discovery process. Previously undisclosed, one of

GlaxoKline's internal documents said, " It would be commercially

unacceptable to include a statement that efficacy had not been

demonstrated, as this would undermine the profile of paroxetine

[Paxil]. " [9]

Many drugs that are assumed to be effective are probably little better

than placebos, but there is no way to know because negative results

are hidden. One clue was provided six years ago by four researchers

who, using the Freedom of Information Act, obtained FDA reviews of

every placebo-controlled clinical trial submitted for initial approval

of the six most widely used antidepressant drugs approved between 1987

and 1999—Prozac, Paxil, Zoloft, Celexa, Serzone, and Effexor.[10] They

found that on average, placebos were 80 percent as effective as the

drugs. The difference between drug and placebo was so small that it

was unlikely to be of any clinical significance. The results were much

the same for all six drugs: all were equally ineffective. But because

favorable results were published and unfavorable results buried (in

this case, within the FDA), the public and the medical profession

believed these drugs were potent antidepressants.

Clinical trials are also biased through designs for research that are

chosen to yield favorable results for sponsors. For example, the

sponsor's drug may be compared with another drug administered at a

dose so low that the sponsor's drug looks more powerful. Or a drug

that is likely to be used by older people will be tested in young

people, so that side effects are less likely to emerge. A common form

of bias stems from the standard practice of comparing a new drug with

a placebo, when the relevant question is how it compares with an

existing drug. In short, it is often possible to make clinical trials

come out pretty much any way you want, which is why it's so important

that investigators be truly disinterested in the outcome of their work.

Conflicts of interest affect more than research. They also directly

shape the way medicine is practiced, through their influence on

practice guidelines issued by professional and governmental bodies,

and through their effects on FDA decisions. A few examples: in a

survey of two hundred expert panels that issued practice guidelines,

one third of the panel members acknowledged that they had some

financial interest in the drugs they considered.[11] In 2004, after

the National Cholesterol Education Program called for sharply lowering

the desired levels of " bad " cholesterol, it was revealed that eight of

nine members of the panel writing the recommendations had financial

ties to the makers of cholesterol-lowering drugs.[12] Of the 170

contributors to the most recent edition of the American Psychiatric

Association's Diagnostic and Statistical Manual of Mental Disorders

(DSM), ninety-five had financial ties to drug companies, including all

of the contributors to the sections on mood disorders and

schizophrenia.[13] Perhaps most important, many members of the

standing committees of experts that advise the FDA on drug approvals

also have financial ties to the pharmaceutical industry.[14]

In recent years, drug companies have perfected a new and highly

effective method to expand their markets. Instead of promoting drugs

to treat diseases, they have begun to promote diseases to fit their

drugs. The strategy is to convince as many people as possible (along

with their doctors, of course) that they have medical conditions that

require long-term drug treatment. Sometimes called

" disease-mongering, " this is a focus of two new books: Melody

sen's Our Daily Meds: How the Pharmaceutical Companies

Transformed Themselves into Slick Marketing Machines and Hooked the

Nation on Prescription Drugs and Lane's Shyness: How

Normal Behavior Became a Sickness.

To promote new or exaggerated conditions, companies give them

serious-sounding names along with abbreviations. Thus, heartburn is

now " gastro-esophageal reflux disease " or GERD; impotence is " erectile

dysfunction " or ED; premenstrual tension is " premenstrual dysphoric

disorder " or PMMD; and shyness is " social anxiety disorder " (no

abbreviation yet). Note that these are ill-defined chronic conditions

that affect essentially normal people, so the market is huge and

easily expanded. For example, a senior marketing executive advised

sales representatives on how to expand the use of Neurontin:

" Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar,

Neurontin for everything. " [15] It seems that the strategy of the drug

marketers—and it has been remarkably successful—is to convince

Americans that there are only two kinds of people: those with medical

conditions that require drug treatment and those who don't know it

yet. While the strategy originated in the industry, it could not be

implemented without the complicity of the medical profession.

Melody sen, who was a reporter for The New York Times, has

written a broad, convincing indictment of the pharmaceutical

industry.[16] She lays out in detail the many ways, both legal and

illegal, that drug companies can create " blockbusters " (drugs with

yearly sales of over a billion dollars) and the essential role that

KOLs play. Her main example is Neurontin, which was initially approved

only for a very narrow use—to treat epilepsy when other drugs failed

to control seizures. By paying academic experts to put their names on

articles extolling Neurontin for other uses—bipolar disease,

post-traumatic stress disorder, insomnia, restless legs syndrome, hot

flashes, migraines, tension headaches, and more—and by funding

conferences at which these uses were promoted, the manufacturer was

able to parlay the drug into a blockbuster, with sales of $2.7 billion

in 2003. The following year, in a case covered extensively by sen

for the Times, Pfizer pleaded guilty to illegal marketing and agreed

to pay $430 million to resolve the criminal and civil charges against

it. A lot of money, but for Pfizer, it was just the cost of doing

business, and well worth it because Neurontin continued to be used

like an all-purpose tonic, generating billions of dollars in annual sales.

Lane's book has a narrower focus—the rapid increase in the

number of psychiatric diagnoses in the American population and in the

use of psychoactive drugs (drugs that affect mental states) to treat

them. Since there are no objective tests for mental illness and the

boundaries between normal and abnormal are often uncertain, psychiatry

is a particularly fertile field for creating new diagnoses or

broadening old ones.[17] Diagnostic criteria are pretty much the

exclusive province of the current edition of the Diagnostic and

Statistical Manual of Mental Disorders, which is the product of a

panel of psychiatrists, most of whom, as I mentioned earlier, had

financial ties to the pharmaceutical industry. Lane, a research

professor of literature at Northwestern University, traces the

evolution of the DSM from its modest beginnings in 1952 as a small,

spiral-bound handbook (DSM-I) to its current 943-page incarnation (the

revised version of DSM-IV) as the undisputed " bible " of psychiatry—the

standard reference for courts, prisons, schools, insurance companies,

emergency rooms, doctors' offices, and medical facilities of all kinds.

Given its importance, you might think that the DSM represents the

authoritative distillation of a large body of scientific evidence. But

Lane, using unpublished records from the archives of the American

Psychiatric Association and interviews with the princi-pals, shows

that it is instead the product of a complex of academic politics,

personal ambition, ideology, and, perhaps most important, the

influence of the pharmaceutical industry. What the DSM lacks is

evidence. Lane quotes one contributor to the DSM-III task force:

There was very little systematic research, and much of the

research that existed was really a hodgepodge—scattered, inconsistent,

and ambiguous. I think the majority of us recognized that the amount

of good, solid science upon which we were making our decisions was

pretty modest.

Lane uses shyness as his case study of disease-mongering in

psychiatry. Shyness as a psychiatric illness made its debut as " social

phobia " in DSM-III in 1980, but was said to be rare. By 1994, when

DSM-IV was published, it had become " social anxiety disorder, " now

said to be extremely common. According to Lane, GlaxoKline,

hoping to boost sales for its antidepressant, Paxil, decided to

promote social anxiety disorder as " a severe medical condition. " In

1999, the company received FDA approval to market the drug for social

anxiety disorder. It launched an extensive media campaign to do it,

including posters in bus shelters across the country showing forlorn

individuals and the words " Imagine being allergic to people..., " and

sales soared. Barry Brand, Paxil's product director, was quoted as

saying, " Every marketer's dream is to find an unidentified or unknown

market and develop it. That's what we were able to do with social

anxiety disorder. "

Some of the biggest blockbusters are psychoactive drugs. The theory

that psychiatric conditions stem from a biochemical imbalance is used

as a justification for their widespread use, even though the theory

has yet to be proved. Children are particularly vulnerable targets.

What parents dare say " No " when a physician says their difficult child

is sick and recommends drug treatment? We are now in the midst of an

apparent epidemic of bipolar disease in children (which seems to be

replacing attention-deficit hyperactivity disorder as the most

publicized condition in childhood), with a forty-fold increase in the

diagnosis between 1994 and 2003.[18] These children are often treated

with multiple drugs off-label, many of which, whatever their other

properties, are sedating, and nearly all of which have potentially

serious side effects.

The problems I've discussed are not limited to psychiatry, although

they reach their most florid form there. Similar conflicts of interest

and biases exist in virtually every field of medicine, particularly

those that rely heavily on drugs or devices. It is simply no longer

possible to believe much of the clinical research that is published,

or to rely on the judgment of trusted physicians or authoritative

medical guidelines. I take no pleasure in this conclusion, which I

reached slowly and reluctantly over my two decades as an editor of

TheNew England Journal of Medicine.

One result of the pervasive bias is that physicians learn to practice

a very drug-intensive style of medicine. Even when changes in

lifestyle would be more effective, doctors and their patients often

believe that for every ailment and discontent there is a drug.

Physicians are also led to believe that the newest, most expensive

brand-name drugs are superior to older drugs or generics, even though

there is seldom any evidence to that effect because sponsors do not

usually compare their drugs with older drugs at equivalent doses. In

addition, physicians, swayed by prestigious medical school faculty,

learn to prescribe drugs for off-label uses without good evidence of

effectiveness.

It is easy to fault drug companies for this situation, and they

certainly deserve a great deal of blame. Most of the big drug

companies have settled charges of fraud, off-label marketing, and

other offenses. TAP Pharmaceuticals, for example, in 2001 pleaded

guilty and agreed to pay $875 million to settle criminal and civil

charges brought under the federal False Claims Act over its fraudulent

marketing of Lupron, a drug used for treatment of prostate cancer. In

addition to GlaxoKline, Pfizer, and TAP, other companies that

have settled charges of fraud include Merck, Eli Lilly, and Abbott.

The costs, while enormous in some cases, are still dwarfed by the

profits generated by these illegal activities, and are therefore not

much of a deterrent. Still, apologists might argue that the

pharmaceutical industry is merely trying to do its primary job—further

the interests of its investors—and sometimes it goes a little too far.

Physicians, medical schools, and professional organizations have no

such excuse, since their only fiduciary responsibility is to patients.

The mission of medical schools and teaching hospitals—and what

justifies their tax-exempt status—is to educate the next generation of

physicians, carry out scientifically important research, and care for

the sickest members of society. It is not to enter into lucrative

commercial alliances with the pharmaceutical industry. As

reprehensible as many industry practices are, I believe the behavior

of much of the medical profession is even more culpable.[19] Drug

companies are not charities; they expect something in return for the

money they spend, and they evidently get it or they wouldn't keep paying.

So many reforms would be necessary to restore integrity to clinical

research and medical practice that they cannot be summarized briefly.

Many would involve congressional legislation and changes in the FDA,

including its drug approval process. But there is clearly also a need

for the medical profession to wean itself from industry money almost

entirely. Although industry–academic collaboration can make important

scientific contributions, it is usually in carrying out basic

research, not clinical trials, and even here, it is arguable whether

it necessitates the personal enrichment of investigators. Members of

medical school faculties who conduct clinical trials should not accept

any payments from drug companies except research support, and that

support should have no strings attached, including control by drug

companies over the design, interpretation, and publication of research

results.

Medical schools and teaching hospitals should rigorously enforce that

rule, and should not enter into deals with companies whose products

members of their faculty are studying. Finally, there is seldom a

legitimate reason for physicians to accept gifts from drug companies,

even small ones, and they should pay for their own meetings and

continuing education.

After much unfavorable publicity, medical schools and professional

organizations are beginning to talk about controlling conflicts of

interest, but so far the response has been tepid. They consistently

refer to " potential " conflicts of interest, as though that were

different from the real thing, and about disclosing and " managing "

them, not about prohibiting them. In short, there seems to be a desire

to eliminate the smell of corruption, while keeping the money.

Breaking the dependence of the medical profession on the

pharmaceutical industry will take more than appointing committees and

other gestures. It will take a sharp break from an extremely lucrative

pattern of behavior. But if the medical profession does not put an end

to this corruption voluntarily, it will lose the confidence of the

public, and the government (not just Senator Grassley) will step in

and impose regulation. No one in medicine wants that.

Notes

[1]Gardiner and Benedict Carey, " Researchers Fail to Reveal

Full Drug Pay, " The New York Times, June 8, 2008.

[2]Most of the information in these paragraphs, including Nemeroff's

quote in the summer of 2004, is drawn from a long letter written by

Senator Grassley to W. Wagner, President of Emory University, on

October 2, 2008.

[3]See Gardiner , " Leading Psychiatrist Didn't Report Drug

Makers' Pay, " The New York Times, October 4, 2008.

[4]Senator Grassley is current investigating Wyeth for paying a

medical writing firm to ghost-write articles favorable to its

hormone-replacement drug Prempro.

[5]Some of this material is drawn from my article " Industry-Sponsored

Clinical Research: A Broken System, " TheJournal of the American

Medical Association, September 3, 2008.

[6] E. Bekelman et al., " Scope and Impact of Financial Conflicts

of Interest in Biomedical Research: A Systematic Review, " The Journal

of the American Medical Association, January 22, 2003.

[7] G. et al., " Institutional Academic–Industry

Relationships, " The Journal of the American Medical Association,

October 17, 2007.

[8]k H. et al., " Selective Publication of Antidepressant

Trials and Its Influence on Apparent Efficacy, " The New England

Journal of Medicine, January 17, 2008.

[9]See Wayne Kondro and Barb Sibbald, " Drug Company Experts Advised

Staff to Withhold Data About SSRI Use in Children, " Canadian Medical

Association Journal, March 2, 2004.

[10]Irving Kirsch et al., " The Emperor's New Drugs: An Analysis of

Antidepressant Medication Data Submitted to the US Food and Drug

Administration, " Prevention & Treatment, July 15, 2002.

[11]Rosie and Jim Giles, " Cash Interests Taint Drug Advice, "

Nature, October 20, 2005.

[12] Tuller, " Seeking a Fuller Picture of Statins, " The New York

Times, July 20, 2004.

[13] Cosgrove et al., " Financial Ties Between DSM-IV Panel Members

and the Pharmaceutical Industry, " Psychotherapy and Psychosomatics,

Vol. 75, No. 3 (2006).

[14]On August 4, 2008, the FDA announced that $50,000 is now the

" maximum personal financial interest an advisor may have in all

companies that may be affected by a particular meeting. " Waivers may

be granted for amounts less than that.

[15]See sen, Our Daily Meds, p. 224.

[16]sen's book is a part of a second wave of books exposing the

deceptive practices of the pharmaceutical industry. The first included

Katharine Greider's The Big Fix: How the Pharmaceutical Industry Rips

Off American Consumers (PublicAffairs, 2003), Merrill Goozner's The

$800 Million Pill: The Truth Behind the Cost of New Drugs (University

of California Press, 2004), Jerome Avorn's Powerful Medicines: The

Benefits, Risks, and Costs of Prescription Drugs (Knopf, 2004),

Abramson's Overdo$ed America: The Broken Promise of American Medicine

(Harper, 2004), and my own The Truth About the Drug Companies:

How They Deceive Us and What to Do About It (Random House, 2004).

[17]See the review by Frederick Crews of Lane's book and two others,

The New York Review, December 6, 2007.

[18]See Gardiner and Benedict Carey, " Researchers Fail to

Reveal Full Drug Pay, " The New York Times, June 8, 2008.

[19]This point is made powerfully in Jerome P. Kassirer's disturbing

book, On the Take: How Medicine's Complicity With Big Business Can

Endanger Your Health (Oxford University Press, 2005).

http://www.nybooks.com/articles/22237