Drug Companies & Doctors: A Story of Corruption -- by Marcia Angell, MD

INTRODUCTION: When an email from Vera Sharav alerted me to the fact that Dr. Marcia Angell, a woman whose writings I have admired for a long time, had just written a book review for the New York Review of Books, I was eager to read it -- AND, after reading it, I immediately decided that I wanted to print it, in its entirety, on HonestMedicine.com.

I want to thank both Patrick Hederman, the New York Review of Books' permissions/rights person, and Dr. Angell herself, who gave me reprint permission.

Although most of my readers probably know this, Dr. Angell is a former editor of the New England Journal of Medicine, a publication that most often is referred to as “prestigious”! For those of you who don’t know of her work, for years, she has been critical of the pharmaceutical industry and its financial ties to researchers, doctors and medical journals –- in fact, to almost every aspect of the conducting and reporting of clinical trials by the pharmaceutical companies.

Currently a Senior Lecturer in the Department of Social Medicine at Harvard Medical School, Dr. Angell is the author of the book, The Truth About Drug Companies: How They Deceive Us and What to Do About It, as well as, of several articles, including “Is Academic Medicine For Sale?,” published in the New England Journal of Medicine, May, 2000. I have quoted from her articles in several of my postings, most notably, in “Is It Possible Some Doctors Still Don’t 'Get' the Extent of Big Pharma’s Financial Ties to 'Standard of Care' Research?"

I am happy to reprint Dr. Angell’s most recent article here, and hope the New York Review of Books  won’t mind that I have provided hyperlinks to actual articles, instead of using footnote form (as is used in print publications.)

On a personal note, The New York Review of Books was one of my husband Tim’s two favorite publications. The other was Fanfare. Whenever he’d come across an article like this one, he’d say, “This one’s for you, Boo.” He always knew which articles I’d love. (You may read about Tim, and his love of books and music, here and here.

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

 

(In this article, Dr. Angell reviews these three books. But her article is far more than just a book review!)

1) Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial -- by Alison Bass, Algonquin Books of Chapel Hill, 260 pp., $24.95

2) Our Daily Meds: How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs -- by Melody Petersen, Sarah Crichton/Farrar, Straus and Giroux, 432 pp., $26.00

3) Shyness: How Normal Behavior Became a Sickness -- by Christopher Lane, Yale University Press, 263 pp., $27.50; $18.00 (paper)

Recently Senator Charles 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. Joseph 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. Charles 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 GlaxoSmithKline. To comply with university and government regulations, he was required to disclose to Emory income from GlaxoSmithKline, 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 GlaxoSmithKline 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 Harris 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 Smith-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 GlaxoSmithKline 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 GlaxoSmithKline), and an indefatigable New York assistant attorney general. They took on GlaxoSmithKline 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 GlaxoSmithKline 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 GlaxoSmithKline'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 Petersen's Our Daily Meds: How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs and Christopher 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 Petersen, 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 Petersen 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.

Christopher 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 principals, 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, GlaxoSmithKline, 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 The New 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 GlaxoSmithKline, 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 Harris 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 James W. Wagner, President of Emory University, on October 2, 2008.

[3]See Gardiner Harris, "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. (See Duff Wilson, “Wyeth’s Use of Medical Ghostwriters Questioned,” The New York Times, December 12, 2008)

[5]Some of this material is drawn from my article "Industry-Sponsored Clinical Research: A Broken System," The Journal of the American Medical Association, September 3, 2008.

[6]Justin 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]Eric G. Campbell et al., "Institutional Academic–Industry Relationships," The Journal of the American Medical Association, October 17, 2007.

[8]Erick H. Turner 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 Taylor and Jim Giles, "Cash Interests Taint Drug Advice," Nature, October 20, 2005.

[12]David Tuller, "Seeking a Fuller Picture of Statins," The New York Times, July 20, 2004. 

[13]Lisa 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 Petersen, Our Daily Meds, p. 224.

[16]Petersen'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 (Public Affairs, 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)

John Abramson's Overdo$ed America: The Broken Promise of American Medicine (HarperCollins, 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 Harris 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).

Comments

[Dan]

This Makes Me Sick

When I heard the word 'war-monger', I had to find out its definition, as I had no idea what that word meant. I knew others could be labeled this word, as I had heard it in the past infrequently directed at others whoever said these two words. So I felt a need to know what these words, and how they affected others who heard them.

Finally, I found the answer: a warmonger is one who promotes war, which is undesirable or discreditable. In this case, one labeled this would have an affinity for what others are reasonably opposed to share the same views:

http://collections.plos.org/plosmedicine/diseasemongering-2006.php

Please review the link above, as there appears to be with some in the pharmaceutical corporate world that are offended by being labeled disease mongers. Often, others are offended by facts that exist as a reaction, it seems. Clearly, disease mongering is real, and activities illustrate this behavior.

Disease mongering is when a large pharmaceutical corporation implements various unethical if not illegal activities in order to sell more of their products by either creating or expanding a particular illness. They do this by creating the perception that others are ill when, in fact, they are not.

Drug companies do this by seeking more of those who should be patients in need of treatment with the drug maker's promoted medications, regardless if they are in need of such treatment or not, clinically.

How this is done by these companies will be described soon.

The drug makers clearly place the needs for their drugs to be for medical conditions whose treatment regimens are to be viewed by others as incomplete or unmet. The companies want to let the public know of the progressive increase for the disease states and how their products treat this illness better than what is available now or has been used in the past. How ironic it seems that drug companies, who make drugs to delay the progression of, or cure diseases with these drugs, wish for others to become as sick as possible to profit from their suffering that they create with disease mongering and sell more pills.

This disease-mongering in fact does occur often to widen the diagnostic boundaries of an illness, disorder, or syndrome by creating awareness of such medical conditions to the public- utilizing in several ways the delivery of fabricated if not baseless information during this process. Usually, the pharmaceutical either creates or expands a disease state by deception directly to consumers, often. Then the consumer, who now believes that they are ill, go see their health care provider. The health care provider, due largely to the unfamiliarity of the patient’s symptoms expressed by the patient, if not the drug the patient is requesting, usually writes a prescription for the drug requested by the patient.

First, let's take a look at this label of disease mongering. It is inappropriate in that, unlike diseases and illnesses, mongering occurs with medical disorders and syndromes as well. It is accurate and factual, however, that disease mongering does occur, but is not limited to diseases that exist, possibly. The disease monger strives to inflate the volume of a disease for which they have drugs to treat for their own financial gain.

There was a book written by Ray Moynihan and Allan Cassels called, "Selling Sickness" in 2005. The book thoroughly described how big pharmaceutical corporations are turning all of us into patients.

Disease mongering progressively continues to create patients with illnesses, disorders, or syndromes that in fact may not exist, yet again, the greater number of people convinced they are afflicted with a certain medical disorder, the better it is for the drug company. What the drug company implements to make sure this happens includes the following:

1. Paying medical journals to publish fabricated clinical trials involving their promoted medications after paying those involved with such a clinical trial to create such fabricated data. That is disease mongering to the health care provider.

2. Subjective screenings, such as those for various mood disorders. These screenings, as well as the affective disorders, which were rare until about 1995, involve leading questions often- created by the drug company. It was around this time that the United States was becoming more of a psychotropic nation.

These screenings that involve the leading questions responded by select groups of people. They are asked these questions by certain disease state support groups who have been converted into front groups after being funded by those big pharma companies who produce drugs for particular mood disorders.

3. Disease creations I: Social Anxiety Disorder, or social phobia: This condition is in the DSM IV which was published in 1994, and some were forced to delete the statement regarding this disorder that said, "Social Anxiety Disorder is not well-established, and requires further study."

Aside from what may be simply amplified introversion, social phobias are likely due to societal dysfunctions and certainly should not be labeled as a pathological condition requiring pharmacological treatment.

4. Disease creations II: Premenstrual dysphoric disorder. I call this a mid-life crisis, yet it was entered by instruction by the APA (American Psychiatric Association) into the DSM (the psychiatrist's bible) in 1993. Anxiety about the inevitable does not require pharmacological treatment.

5. Direct to Consumer Advertising:. Most memorable were those commercials for erectile dysfunction. Their absurdness in creating these commercials appears to have multiple psychotic components:

A healthy man who could probably run a marathon is having a decent time with his wife at some upper- middle class location. He is smiling all the time. Because now, his marriage is secure due to his ability to copulate- which was apparently absent before this wonder drug entered his system. Of course, it is not possible to have a happy marriage without intercourse, right?

Then there are other conditions which are entirely natural in the human lifespan, yet have been determined to be diseases by those who can profit off of these lifespan events. Examples include osteoporosis and menopause, as well as erectile dysfunction. It’s insane the FDA approves pharmaceuticals for these natural events that occur normally in a human being.

Finally, there are the required medical guidelines for various disease states, such as dyslipidemia. Drug companies that make medications to treat this disease are more than happy to support the financial needs involved in creating these guidelines. Dyslipidemia, for example:

Publications such as the Lipid Letter, and Lipid Management, both offered more aggressive management of the lipid profiles of the patients of the readers. And both publications were funded completely by those big pharma companies that promote statins. Same with cholesterol screenings that occur often.

A myth is something unproven. A false belief, or invented story.

Disease Mongering is not a myth. Large pharmaceutical corporations promote illness and disease- not desired by anyone and discredited by many, and these companies do this for profit and profit only.

I worked for three of the largest pharmaceutical companies in the world for over a decade, and the disease mongering protocols were similar if not identical with all of these companies,

Dan Abshear

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[Dan]

The Fallacies Associated With ‘Me-Too’ Pharmaceuticals
“But corruption is neither need based nor greed based. It’s simply opportunity based.” -----Billy Tauzin, president and C.E.O. of PhRMA, the pharmaceutical industry’s most powerful lobbying group, as Mr. Tauzin stated in Boston recently.

It has been said by others that the pharmaceutical industry should not have government regulation or interference from anyone interfering with their autonomy- because that would drastically limit if not eliminate their progressive innovation regarding the restoration of the health of others with their drugs.
Also what has been stated by this industry that their internal controls prevent wrongdoing, so there is no need o be under surveillance. So, according to some, the public’s health would be potentially unfulfilled and possibly harmed without the copious innovative products of this industry. As with other issues we face as citizens, this is another attempt by an industry that is constantly attempting to integrate fabricated fear in our minds- void of any proof or reason, and this is a fallacy.
As it has turned out, the pharmaceutical industry’s lack of innovation in particular has happened and they have appeared to do this on their own, overall, those innovators and lifesavers of the past.
Over the last several years, those few meds created and FDA approved with true therapeutic advantages happened by discovery with government involvement. Of all drugs approved by the FDA, few offer any clear clinical advantages over other drugs for certain patients. The approved drugs, called new chemical entities, that have been FDA approved lately which were developed by drug companies, possess microscopic therapeutic advantages over existing drugs that are presently prescribed for particular patients.
This inefficient drug development process by the pharmaceutical industry has created what is now the dominant development strategy of drug companies, and this strategy is known as the intentional development of what are phrased, ‘me too’ drugs.
These drugs essentially are small molecular variations of the original molecule in a particular class of medications. In other words, they tweak the original molecule in order to obtain patent rights for their now new drug project. That’s why you have a half a dozen statins or ARBs available to you. The are all equivalent, biochemically.
This ‘me too’ objective of drug companies now accounts, I believe, for about 80 percent of the research budgets of drug companies. And because the FDA only requires a pending drug awaiting approval to only be slightly superior to a placebo, the copies of drugs that already exist are approved by the FDA.
While unnecessary, these me too drugs are selected by the drug company for their potential blockbuster status as well as the speculated growth of a particular market or disease state, which means the drug company who develops a me too drug hopes to eventually make over 1 billion dollars a year on such a drug, at least. For example, statin drugs, for high cholesterol patients, is a multi- billion dollar market. As a result, there are several statin meds now available for use by doctors to prescribe to their patients. While unnecessary for the health of others, this is where the research dollars are going with those in the pharmaceutical company.
As aggressive marketers, the makers of these meds are suspected of doing a bit of publication planning, it is suspected. They create clinical trials to falsely claim superiority of their newly approved me too drug over all the other drugs in a particular class both during and after the creation of these me too drugs. Yet again, if they are in the same therapeutic class, they are all essentially the same regarding efficacy and safety.
Also, other classes of meds with several me too drugs may include SSRI anti-depressant drugs, as well as those meds for hypertension. There may be a dozen drugs in a particular class of medications that are all essentially the same in regards to their treatment abilities for patients with such disease states that they treat.
Now, there may be cases where a patient tolerates one drug in a class over another for unknown reasons, so in these few cases, some me too drugs occasionally are beneficial for patients for some reason or another, but should absolutely not be a primary objective of the drug companies to create them as often as they do.
Instead, true innovation and discovery should be the focus of pharmaceutical companies, and it does not appear to be the focus of the pharmaceutical industry presently. It appears that, thanks to the Bayh-Dole Act of 1980 in the United States, the pharmaceutical industry is allowed to license newly created synthetic small molecules from those in the academic world, and then proceed with development of another’s creation that the pharmaceutical company will claim as their innovation to the public.
Further vexing is that competition in the pharmaceutical industry amazingly does not and has not been of any financial benefit for the consumer, as competition normally does create. This fact is greatly demonstrated with other industries and is the apex of business operations in the United States.
This pharmaceutical industry model is an exception to typical business operations, and the reason for this remains an unknown, as far as the etiology of those who take their drugs being deprived of expected cost reduction in this costly environment of drug spending. So a drug company comes out with a me too drug, and claims it is unique rather deceptively, so there is no cost advantage for the consumer.
This progressive marketing paradigm of the pharmaceutical industry, such as the creation of me too meds solely created for their own profit, clearly illustrates their focus on their avoidance of true research and discovery for the sake of their own profit viewed by them as of being of greater importance.
Innovation, along with ethics, use to define this pharmaceutical industry. Sadly, it seems this is not the case today, which ultimately and potentially deprives potential treatment methods for the public health. Perhaps more cures and more therapeutic options would be available if the objectives of the pharmaceutical industry were for the benefit of the health of others.
Hopefully, such historical qualities of drug companies will return some time, in time.
“Most people are other people. Their thoughts are someone else’s opinions, their lives a mimicry, their passions a quotation.” --- Oscar Wilde
Dan Abshear
Author’s note: What has been written was based on information and belief.

[Dan]

The Atrophy Of Objectivity

If I were to rate the corruptive tactics performed by big pharmaceutical companies during my intimate experience with them , the frequent and intentional strategy of implementing fabricated and unreliable results of clinical trials performed by others possibly tops the list of corruptive tactics by the pharmaceutical industry that sponsors such trials. By this atrophy of the scientific method absent of authenticity that has been known to occur, harm and damage is possibly done to the health of the public.
Most would agree that the science of research should be sound and as aseptic as possible- completely free of deliberate and reckless interference. However, it appears, money and increased profits can be a catalyst for disregard for human health with the clinical trial process that is largely unregulated.
This is particularly a factor on post-marketing studies of various pharmaceutical companies, as some pharmaceutical corporations seem to be deliberately conducting nothing less than seeding trials- with about a 50 percent tax credit for these trial sponsors. Trials that are in fact pointless and void of scientific benefit.
Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of drugs and devices to benefit mankind. Then, in 1980, the Bayh-Dole Act, Public Law 96-517,was created, which allowed for such places with their researchers to profit off of their discoveries that were performed for pharmaceutical companies and others in the past.
Furthermore, such academic institutions were coerced to license patented inventions to those pharmaceutical companies that will then commercialize these discoveries paid for in large part by the taxpayers who funded this research to a degree.
This resulted in the creation of for-profit research trial sites without any academic affiliation that are called Contract Research Organizations. CROS utilize primarily community patient care clinics whose staff are absent of any research training compared with the former researchers that existed decades ago. Because of this structure, the clinical trial investigators of these pharmaceutical sponsored trials are likely novice compared with academic researchers.
This, of course, happens with intent by the sponsor who can and does control all aspects of the clinical trial protocol at the site locations of a clinical trial that the pharmaceutical company structures and even gives the trial the title they want for their marketing purposes.
These quite numerous CROS are in fact for- profit, with some CROs making billions of dollars a year, and this market continues to grow.
The trials conducted at such places again are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their particular drug chosen to be studied. Etiology for their deception regarding this manipulation is because the pharmaceutical company that sponsors such a trial is basically creating a marketing tool for this drug of theirs to be studied in this manner. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this protocol of the sponsor ensures favorable results of the sponsor’s medication that is involved in the clinical trial they clearly own.
These activities are again believed to be absent of true or applied regulation to any degree, and therefore have the autonomy to create whatever they want to benefit the pharmaceutical sponsor. There likely is a collusive relationship between the sites, the CRO, and the sponsor, as this whole system is planned beforehand by the pharmaceutical sponsor of their clinical trial to again be utilized to increase the market share of the drug studied that they promote.
Guest authorship has been known to be aggressively recruited by sponsors by paying a known opinion leader to sign off on the completed clinical trial. Furthermore, the pharmaceutical sponsor recruits investigators to be used for this function of what ultimately is a fabricated clinical trial protocol. The trial manuscript and protocol design is prepared by those employed by the drug company sponsor upon specific direction of this sponsor on how this should be prepared.
The medical program coordinator of a particular sponsored trial is an actual employee of the sponsoring drug company and also may act as the publisher, manuscript version reviewer, and the clinical trial director who works with the drug company’s hired CRO editors whose objectives are to benefit the sponsor. Typical and ultimate cost of the final manuscript of the trial to the sponsor created by the hired CRO and the recruited ghostwriters exceeds 1000 dollars per page, some have said.
Merck engages in this behavior, which shocked many, as they were always viewed as an ethical pharmaceutical company that always placed patients over profits. Apparently, this is no longer the case. There are other well known and large pharmaceutical corporations that consider this plan of action standard operating procedures to ensure growth of their drugs.
Further disturbing is that once the creation of the trials is completed, the research paper is often composed with specific directions by the sponsor to writers known again as ghostwriters. These people are usually not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers.
One does not need research training or certification in order to perform this function. Rarely do clinical trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented by the pharmaceutical sponsor. Also, these hired mystery writers are known to make about 100 grand a year performing this deception full time.
This activity removes accountability and authenticity of the fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring again a known thought leader as an author to have their name be placed on the trial, while this hired author likely had absolutely no involvement with the trial, or even reviewing the trial is not asked or required by the hired author, others have said.
To have the trial published, the sponsor has been known to pay an obscure journal, and the sponsor bribes the journal in a few ways, such as the sponsor purchasing from a selected journal thousands of reprints of their study from the journal, for example. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers mentioned earlier and progressively growing research sites to receive the support the pharmaceutical industry. So benefits of pharmaceuticals that are studied in such a malicious way potentially can harm patients and their treatment options along with clear safety risks as a result of this process.

The purchased reprints of the fabricated clinical trial are then bought by the sponsor of the study from the medical journal they hired to publish this trial. The reprints are eventually distributed to the sponsor’s sales force to share the content with prescribers, with the sales force completely unaware about this manipulation that has happened with such a trial that benefits the drug they promote for their employer. As a bonus, the sponsor may agree to pay the chosen medical journal to advertise their products to be placed in this journal as well.
Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns, as stated previously. If so, our health care treatment options with drugs that are claimed to have benefits that are absent have now become unreliable in large part due to such corruptive situations. Not to mention the absence of objectivity that has been intentionally eliminated with trials produced in this way.
More now than ever, meds are removed from the market or are given black box warnings due to the damaging effects of drugs approved by the FDA. We as citizens need to dig deep and ask why this is happening.
Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should be conducted in a way that the sponsor cannot in any way interfere in such ways described in this article, which would require independent clinical trial sites with no involvement from the maker of the drug studied in a clinical trial.
And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health.
Knowledge is power, and is also possibly a lifesaver.
“Ethics and Science need to shake hands.” ……. Richard Cabot
Dan Abshear
Author’s note: What has been written was based upon information and belief.

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