from "Ethics and the Pharmaceutical Industry," Cambridge University Press (2005), MA Santoro and TM Gorrie, eds.
"Exploratory research does not, in fact, take place within therapeutic categories but is conducted on a mechanistic and methodological basis. An intensive and multifaceted concentration on immunopharmacological questions with a view, for instance, to developing new treatment options for [HIV/AIDS] could quite conceivably result in effective agents for the treatment of some of the less common autoimmune diseases. Because of economic pressures to which many companies are exposed, however, there is a danger that such drugs will not be developed. What we have here is an obvious conflict of goals between medical or Hippocratic ethics, on the one hand, and corporate ethics--which call for maximizing profits without regard for patients in need and focus on shareholder value--on the other."
-Jürgen Drews, MD, former President of Global R&D at Hoffmann-La Roche, Chairman of the Bd of Genaissance Pharm. Inc., Partner of Bear Stearns Health Innoventure Fund LLC, co-founder of International Biomedicine Management Partners, Inc., and adjunct professor of Genetics at University of Medicine and Dentistry in New Jersey
New evidence keeps emerging that the medical profession has sold its soul in exchange for what can only be described as bribes from the manufacturers of drugs and medical devices. It is long past time for leading medical institutions and professional societies to adopt stronger ground rules to control the noxious influence of industry money on what doctors prescribe for their patients.
Last week two new cases came to light that reveal the lengths to which companies will go to buy influence with doctors, pharmacists and other medical professionals. Reed Abelson reported in The Times on Jan. 24 about a whistle-blower's lawsuit alleging that Medtronic had paid tens of millions of dollars in recent years to surgeons in a position to use and recommend its medical devices. In one particularly egregious example, a prominent Wisconsin surgeon received $400,000 for just eight days of consulting.
In last Saturday's Times, Gardiner Harris and Robert Pear revealed that a Danish company paid a pharmacist, doctors' assistants and a drug store chain to switch diabetic patients to the company's high-priced insulin products.
In the wake of past reports of industry's influence over prescribing practices, medical and industry groups have issued guidelines defining appropriate behavior. But as an article in The Journal of the American Medical Association made clear last week, these guidelines are far too weak.
The influential authors called for a complete ban on all gifts, free meals and payments for attending meetings. They urged doctors to reject free drug samples because they are a powerful incentive to use medicines that are expensive but not more effective. And they called for a ban on consulting arrangements that entail no specific scientific duties.
These proposals are hardly onerous. Kaiser Permanente, a California-based managed care group, has adopted nearly all of the recommendations. Its doctors prescribe heavily marketed medicines far less frequently than most other doctors.
The critical issue is that doctors must have the best interests of their patients at heart in prescribing drugs or recommending medical devices. Their judgment must not be clouded by financial self-interest or the desire to please industrial benefactors.
Health Industry Practices That Create Conflicts of Interest
A Policy Proposal for Academic Medical Centers
Troyen A. Brennan, MD, MPH; David J. Rothman, PhD; Linda Blank; David Blumenthal, MD, MPP; Susan C. Chimonas, PhD; Jordan J. Cohen, MD; Janlori Goldman, JD; Jerome P. Kassirer, MD; Harry Kimball, MD; James Naughton, MD; Neil Smelser, PhD
Conflicts of interest between physicians' commitment to patientcare and the desire of pharmaceutical companies and their representativesto sell their products pose challenges to the principles ofmedical professionalism. These conflicts occur when physicianshave motives or are in situations for which reasonable observerscould conclude that the moral requirements of the physician'sroles are or will be compromised. Although physician groups,the manufacturers, and the federal government have institutedself-regulation of marketing, research in the psychology andsocial science of gift receipt and giving indicates that currentcontrols will not satisfactorily protect the interests of patients.More stringent regulation is necessary, including the eliminationor modification of common practices related to small gifts,pharmaceutical samples, continuing medical education, fundsfor physician travel, speakers bureaus, ghostwriting, and consultingand research contracts. We propose a policy under which academicmedical centers would take the lead in eliminating the conflictsof interest that still characterize the relationship betweenphysicians and the health care industry.
Author Affiliations: Harvard Medical School, Boston, Mass (Drs Brennan and Blumenthal); Institute on Medicine as a Profession/Columbia University College of Physicians and Surgeons, New York, NY (Drs Rothman, Chimonas, and Goldman); Association of American Medical Colleges, Washington, DC (Dr Cohen and Ms Blank); Tufts University School of Medicine, Boston, Mass (Dr Kassirer); University of Washington School of Medicine, Seattle (Dr Kimball); Alliance Medical Group and University of California San Francisco School of Medicine, San Francisco (Dr Naughton); and University of California, Berkeley (Dr Smelser).
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Limits Are Sought
For Doctors' Ties
To Drug Makers
By ANNA WILDE MATHEWS Staff Reporter of THE WALL STREET JOURNAL January 25, 2006; Page A3
A group of academics called for stringent limits on the ties between drug companies and doctors, saying in an article published in the Journal of the American Medical Association that the current relationships lead to conflicts of interest.
The medical profession's standing is "jeopardized by allowing obvious conflicts to continue," and academic medical centers should take the lead in reforming them, the JAMA article said. The writers, from Harvard University, Columbia University, the University of California at Berkeley and other institutions, echoed concerns expressed with increasing frequency by medical-journal editors, professors and some doctors.
The authors want to end all free drug samples and gifts to doctors from pharmaceutical and medical-device makers, including payments for travel to meetings, meals and attending medical-education sessions. The article calls for companies to stop directly funding medical-education sessions because they could lead to a mingling of promotional and educational goals. The authors also called on medical-school faculty to stop serving as speakers for companies and using industry-paid ghostwriters.
The writers want new limits on industry consulting and research contracts, including a prohibition on "so-called 'no strings attached' grants or gifts to individual researchers." Such agreements should be disclosed on a public Web site, they said, because company-funded research is likely to lead to more positive results and "on occasion companies have restricted the dissemination of research results unfavorable to their products."
The Pharmaceutical Research and Manufacturers of America, an industry trade group, said in a prepared statement that it already has adopted voluntary guidelines limiting gifts to doctors, and other government and standards-setting groups have rules on medical education. "The current rules...really ought to address the concerns that they've got," said Scott Lassman, an assistant general counsel for the group. The group believes its guidelines "have been extremely effective," he said, even though they are voluntary.
The American Medical Association said that it has ethics guidance for doctors that suggests limits on gifts. It also said it has been "examining and updating" the policy.
But members of the group that wrote the JAMA article dismissed the current guidelines from medical and other groups as inadequate, particularly concerning disclosure of relationships. "They are weak, they lack enforcement, they lack monitoring," said David Rothman, a professor at Columbia University and president of the nonprofit Institute on Medicine as a Profession. "Transparency goes way beyond disclosure."
Jordan Cohen, an author of the article and president of the Association of American Medical Colleges, said he planned to bring up the article with the organization's executive council; his work on it wasn't on behalf of the association. "The public has become quite appropriately concerned," said Dr. Cohen. But, he said, he expects "resistance" from universities and doctors wary of losing a substantial income stream.
The Center for Science in the Public Interest (CSPI) is calling on the editors of Science and Nature, the world’s two most prestigious science publications, to strengthen their conflict-of-interest disclosure policies.
Both Drs. Hwang Woo-Suk of Seoul National University and Gerald Schatten of the University of Pittsburgh have numerous stem cell patent applications on file at the World Intellectual Property Organization and the U.S. Patent and Trademark Office. None were disclosed in the March 2004 and June 2005 Science articles describing somatic cell nuclear transfer or the August 2005 Nature article describing the cloning of Snuppy the Afghan hound.
CSPI Integrity in Science director Merrill Goozner called on the editors to strengthen their conflict of interest disclosure policies by requiring authors to declare all financial conflicts of interest, including patents and patent applications, whose value may be affected by publication; to tell authors they will publish those conflicts; and to impose a three-year ban on authors who fail to disclose any financial conflicts. The government-sponsored journal Environmental Health Perspectives has such a ban.
"Science and Nature should take the lead in the wake of this scandal," said Goozner. "In a world where financial incentives can warp the scientific enterprise just as much as the lust for scientific prestige, it is incumbent that journal editors have strict conflict-of-interest disclosure policies. And, given the voluntary nature of disclosure, they should have teeth like a three-year ban on publishing for failing to disclose."
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Books mentioned in this composite review:
The Truth About the Drug Companies: How They Deceive Us and What to Do About It By Marcia Angell, MD Random House, 2004. $24.95
On the Take: How America’s Complicity With Big Business Can Endanger Your Health By Jerome P. Kassirer, MD Oxford University Press, 2004. $28.00
Overdosed America: The Broken Promise of American Medicine By John Abramson, MD HarperCollins, 2005. $24.95
The $800 Million Pill: The Truth Behind the Cost of New Drugs By Merrill Goozner University of California Press, 2004. $24.95
University Inc.: The Corruption of Higher Education By Jennifer Washburn Basic Books, 2005. $26.00
Powerful Medicines: The Benefits, Risks and Costs of Prescription Drugs By Jerry Avorn Alfred A. Knopf, 2004. $27.50
Two of the year's most stinging anti-drug-industry analyses come from former editors in chief of The New England Journal of Medicine. Marcia Angell’s ''The Truth About the Drug Companies: How They Deceive Us and What to Do About It'' is one. Jerome P. Kassirer is the other; the title of his book, ''On the Take: How America's Complicity With Big Business Can Endanger Your Health'' (Oxford University, $26), says it all. And these rising voices of disillusionment have the credentials to back up their scorn. Jerry Avorn, a professor at Harvard Medical School, helps decide what drugs are used in Boston's Brigham and Women's Hospital. His entertaining jeremiad, ''Powerful Medicines: The Benefits, Risks and Costs of Prescription Drugs,'' cuts through the haze, arguing persuasively that Americans are paying an enormous amount of money for some very mediocre medicines. John Abramson was a doctor in family practice until, as he recounts in ''Overdosed America: The Broken Promise of American Medicine'' (HarperCollins, $24.95), he began to detect what might politely be called statistical legerdemain in articles promoting new drugs in the aforementioned New England Journal.
These books are not simply diatribes against high prices and lagging development of new medicines. More disturbingly, the authors contend that the drug industry has polluted the scientific basis of modern medicine with rigged market-driven clinical studies that inflate the effectiveness of new, high-priced drugs while concealing their risks to patient safety. Angell's occasionally strident language, laced with terms like ''bribes and kickbacks'' and ''faux research'' seems hyperbolic -- until you consider that one week's worth of headlines.
The reasons for the transformation of the industry's image from life-saving pioneer to robber baron are many. But at root is a profound shift in the hierarchy of influence and decision making within the companies themselves over the last two decades, as the traditional emphasis on research and development has given way to marketing. The change is everywhere apparent: in the background of many company executives, in the annual balance sheets (in 2001, Angell estimates industrywide marketing budgets at $54 billion, almost double research-and-development outlays, which the industry lobby puts at $30 billion), in the army of 88,000 salesmen (or detailers), trained to bird-dog doctors and persuade them to prescribe their company's drugs. Though much drug industry research remains outstanding, the system rewards what Avorn calls ''trivial pseudo-innovation''; shifting the emphasis from research to marketing was, he says, ''just responding rationally to the legal, regulatory and economic pressures of a marketplace that had become perverse.''
Angell, who gives a vivid historical context, dates the ''watershed year'' to 1980, on the cusp of a era in which it became ''not only reputable to be wealthy, but something close to virtuous.'' The Bayh-Dole Act of 1980 basically turned academic labs into farm teams for industry research, allowing publicly funded researchers in academic institutions (where much of the real enterprise and innovation occur) to patent their discoveries and license them to the private sector; the law has created a thicket of licensing and royalty relationships, wink-and-nod consultancies and conflicts of interest. As Angell tellingly relates, the authors of one New England Journal article collectively owned up to so many financial conflicts that they had to be listed separately on a Web site. The headline on the editorial she wrote about the episode was ''Is Academic Medicine for Sale?'' One cynical reader replied: ''No. The current owner is very happy with it.''
Then there was was the Hatch-Waxman Act of 1984, which did what it was ostensibly designed to do, make it easier for generic drug makers to put cheaper medicines on the market -- but at enormous cost to the consumer. In Angell's view, Hatch-Waxman was a Trojan horse bill; its loopholes meant that pharmaceutical companies could, with patent infringement suits costing, say, a mere $5 million, extend government-granted monopolies on popular drugs like Prilosec and Claritin, in some cases for more than four years, yielding them billions of dollars in additional revenue.
It gets worse. Laws passed in the 1990's gave drug companies extraordinary financial influence over their primary regulator, the Food and Drug Administration, through so-called user's fees to expedite reviews of new drugs. And both Angell and Avorn quote Senator Bill Frist's devastatingly candid remark revealing that one respected candidate for the agency's top job in 2002 apparently lost industry support because ''there was a great deal of concern that he put too much emphasis on safety.''
As for the recent Medicare reform bill, with its prescription drug benefit, Angell considers the measure a huge windfall for industry, because it explicitly forbids Medicare to bargain on prices. Indeed, Angell foresees a grim day of reckoning, and calls for its immediate repeal.
Pharmaceutical Research and Manufacturers of America, the industry's lobbying group, has tirelessly argued that high drug prices are needed to support the high-risk endeavor of drug discovery and development. Yes, the business is risky. But Angell gives us good reason to dispute the much-quoted figure of $802 million as the average cost for developing a new drug, and the assertions of innovative research and development. She cites studies showing that between 1998 and 2002, 415 new drugs received F.D.A. approval; only 133 were ''new molecular entities,'' or genuinely novel compounds, and of those, only 58 -- or 14 percent of all new drugs for the five-year period -- were considered likely by the F.D.A. to be ''a significant improvement'' over existing products.
Avorn covers much the same ground, but comes at it by statistical analysis of drug effectiveness and safety. As a ''pharmacoepidemiologist,'' he studies large patient databases to determine how often certain medications are used and how well they work. His watchword is ''evidence-based medicine'' -- the use of randomized controlled clinical trials, in which participants are randomly assigned to receive, for example, a drug being tested or a dummy pill, or of large-scale epidemiological studies to determine with statistical rigor exactly which drugs are safest, most effective and, increasingly, most cost-effective. He laments that ''we have begun to allow the marketplace to usurp the place of evidence in determining which treatments are effective.'' The marketplace has also been very good about playing down side effects: Avorn's accounts of the systematic ''obfuscation of risk'' for two drugs ultimately withdrawn from the market, the diet drug Redux and the diabetes drug Rezulin, are stomach-turning in their detailing of corporate indifference.
What to do? Angell's most urgent recommendation (among many) is to establish an independent mechanism within the National Institutes of Health, for testing prescription drugs against each other without involving the industry. Avorn, in arguing for more evidence-based medicine, lays out several nonprofit and for-profit scenarios for precisely that kind of independent, data-driven drug assessment. (My own view is that there will be a McDonald's on Mars before drug companies relinquish head-to-head clinical testing of their products -- precisely because high-quality data is a poison pill to most of their marketing.)
In 1906, Upton Sinclair documented abuses in the meat-packing industry; his book, ''The Jungle,'' catalyzed outrage and helped lead to the Food and Drug Act of 1906, which set the first national food and drug regulatory processes. I doubt either of these books will have a similar impact. Public policy these days is mostly driven by events, not books. My guess is that it will take the pharmaceutical equivalent of a plane crash -- perhaps a devastating new influenza epidemic, a disease for which, as this flu season's experience makes painfully clear, fewer and fewer companies bother to make vaccines; or a hugely successful life-saving cancer drug whose high cost would make the economic wall between the haves (who get to live) and the have-nots (who don't) politically unsustainable. That unpleasant day of reckoning is almost upon us. These fine books go a long way in explaining how our medicine, once so vaunted, has become so bitter. The authors of one scientific article had so many conflicts, they needed a web site to list them.
Many thanks to Stephen Hall for some of the text in the first part of this composite review. Apparently he has a new book out: ''Merchants of Immortality: Chasing the Dream of Human Life Extension.''
NOTE: While the concerns of commercial bias, corruption and kick-backs expressed here are serious and well-documented, they in no way endorse or support a thesis which denies any of the following:
(1) That HIV is necessary in the causation of the immune deficiency syndrome called AIDS; (2) That HIV antibody tests accurately diagnose HIV in up to 98% of infected individuals after 4-12 weeks of infection; (3) That antiretroviral medicines, while far from perfect, improve immune function and can extend life; (4) That HIV is heterosexually as well as homosexually transmitted; (5) That condoms, when used properly, can prevent HIV transmission; (6) That HIV/AIDS is one of many serious public health challenges in many regions of Africa, Asia, and the Caribbean.
