As I posted yesterday, the increasingly noisy debate about health care reform in the US has not dealt much with the issues we often discuss on Health Care Renewal. These include problems in how health care organizations are led which threaten physicians' and other health care professionals' core values using tactics including perverse incentives, deception, and intimidation.
Last night, however, President Obama held a news conference mostly devoted to health care issues, in which he stressed the importance of changing not just how health insurance works, but how health care decisions are made. As Newsweek's "The Gaggle" blog reported,

Can I guarantee that there are going to be no changes in the health care delivery system? No. The whole point of this is to try to encourage changes that work for the American people and make them healthier. The government already is making some of these decisions. More importantly, insurance companies right now are making those decisions. And part of what we want to do is to make sure that those decisions are being made by doctors and medical experts based on evidence, based on what works, because that's not how it's working right now.

So what the President seems to be advocating is making health care more evidence-based, perhaps in the formal sense of evidence-based medicine.

As a card-carrying evidence-based medicine advocate, I certainly agree, but let me reiterate that evidence-based medicine is not just medicine based on some sort of evidence. As Dr David Sackett, and colleagues wrote [Sackett DL, Rosenberg WM, Muir Gray JA, Haynes RB, Richardson WS. Evidence-based medicine; what it is and what it isn't. BMJ 1996; 312: 71-72. Link here. ]

Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research. By individual clinical expertise we mean the proficiency and judgment that individual clinicians acquire through clinical experience and clinical practice. Increased expertise is reflected in many ways, but especially in more effective and efficient diagnosis and in the more thoughtful identification and compassionate use of individual patients' predicaments, rights, and preferences in making clinical decisions about their care. By best available external clinical evidence we mean clinically relevant research, often from the basic sciences of medicine, but especially from patient centred clinical research into the accuracy and precision of diagnostic tests (including the clinical examination), the power of prognostic markers, and the efficacy and safety of therapeutic, rehabilitative, and preventive regimens.

Furthermore,

Evidence based medicine is not 'cookbook' medicine. Because it requires a bottom up approach that integrates the best external evidence with individual clinical expertise and patients' choice, it cannot result in slavish, cookbook approaches to individual patient care. External clinical evidence can inform, but can never replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision.

One can find other definitions of EBM, but nearly all emphasize that the approach is designed to appropriately apply results from the best clinical research, critically reviewed, to the individual patient, taking into account that patient's clinical characteristics and personal values.

So far, so good. I believe the proper application of "real" (as described above) evidence-based medicine has the potential to improve patient outcomes while moderating health care costs. However, we have pointed out how problems arising from concentration and abuse of power in health care threaten the evidence-based medical ideal.

First, there are major problems with the development of the sort of clinical research evidence required by the EBM process. We have discussed how clinical research is frequently manipulated by those with vested interests in producing results that favor the products or services that they sell. The critical review process inherent in EBM is meant to cope with less than optimally designed and implemented research. However, the process was designed to cope with honest mistakes and inevitable trade-offs, not deliberate manipulation by vested interests.

Worse, we have discussed how vested interests may engineer the suppression of research when manipulation fails to produce the desired results. The EBM process assumes that the research on which decisions should be based is an unbiased sample of research that was done (and done to advance science, not commercial or ideological interests). When research whose results are unwanted by vested interests is suppressed, the resulting distortion of the evidence base may irretrievably bias the EBM process.

Finally, we have posted about how vested interests have distorted the discussion, dissemination, and teaching of the results of clinical research. They may develop systematic stealth marketing campaigns, often employing supposed "key opinion leaders," who are paid on the side by marketers, and using "medical education and communication companies"as marketing fronts whose publication strategies include deceptive tactics such as "ghost-writing."

Thus, a rising tide of "pseudo-evidence based medicine" threatens to overwhelm even the most conscientious physicians trying to practice evidence-based medicine.

So, while I applaud President Obama's advocacy of reforming health care to emphasize what the best evidence suggests really works, I do not think this effort will get far unless we deal with the rising tide of pseudo-evidence based medicine. As a minimum, we need full and detailed disclosure of all the relationships among vested interests and medical research and education, and a much greater role for research and education that is not subsidized by corporations bent on using research and education to market their products and services.

We have posted multiple times about Avandia (rosiglitazone), GlaxoSmithKline's star-crossed glucose-lowering drug. While Avandia has received considerable media coverage, we focused on two questions: 1 - what are the benefits and harms of rosiglitazone as a treatment of type 2 diabetes, and therefore for which patients under what circumstances should this drug be used? 2 - what barriers have prevented physicians and patients from getting the best possible answer to the first question, and what can be done about them? (See recent post here.)

In particular, the Avandia case has illustrated how those with vested interests in the success of a health care product have done their best to obscure information that might threaten its success, even when doing so obscures the information that physicians and patients need to make the best possible decisions. At one point, (in 2007, no less) we called this the "Avandia spin cycle."

Avandia once again has been in the news after the US Food and Drug Administration's hearings on the safety of the drug. These hearings were so well covered in the media that a lengthy summary would be superfluous. However, their main points demonstrated the persistence of the Avandia spin cycle:
- An FDA reviewer felt that "the company's misreadings of the ... Record trial ... were so profound, he concluded, that they 'suggest serious flaws with trial conduct.'" (per Gardiner Harris writing in the New York Times)
-A former FDA reviewer "withheld from regulators a study showing its Avandia diabetes drug may cause heart attacks." (per Bloomberg News)
- GlaxoSmithKline's forerunner SmithKline Beecham "secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda." However, "the study also provided clear signs that it [Avandia] was riskier to the heart. But instead of publishing the results, the company spent the next 11 years trying to cover them up." (per Gardiner Harris writing in the New York Times.
- "Government experts and a panel of medical advisers repeatedly voiced skepticism on Tuesday about the trustworthiness of GlaxoSmithKline, which makes the controversial diabetes drug Avandia." (per Gardiner Harris again writing in the New York Times.)

So the Avandia saga has brought to the front pages the concerns we have had with suppression and manipulation of clinical research, especially when pursued by health care organizations with vested interests in the results of specific research projects coming out a certain way, and how they have been enabled by those with conflicts of interest. Doctors thus should be worried whether those of us who try to practice evidence-based medicine have been fooled into practicing pseudo-evidence-based-medicine.

Those commenting on the story focused on the need for transparency when clinical research is funded and run by the corporations whose products are being evaluated.
- "GlaxoSmithKline, the maker of Avandia, can't be trusted to report adverse clinical results fairly. The company must be watched like a hawk as additional trials that it sponsors go forward." (NY Times editorial)
- "What America should demand in return for ... [generous patent] protection is that the FDA be able to make an honest evaluation of the efficacy of drugs. When drug companies make this impossible by suppressing test results, not only do they violate their fundamental obligation of honesty with the public, their customers and their regulator, but they also break the bargain they have struck in return for the protection of their intellectual capital." (Former NY Attorney General Eliot Spitzer in Slate.)

Instead, as I have written before, maybe we ought to consider whether those with vested interests in drugs or devices ought to be running clinical research meant to evaluate their own products.

Ironically, while this discussion of how the Avandia spin cycle first began to revolve were going on, others were still trying to add revolutions (per minute). In particular, a Reuters story noted:

Three influential groups of doctors who treat diabetes urged patients not to stop taking Avandia, saying on Thursday that while news about the controversial drug may be frightening, it would be worse to suddenly stop taking it.

That is odd, given that Avandia has never been shown to improve clinical outcomes for patients with diabetes, and that there are many other drugs that control blood sugar which appear to be safer. But wait, there is more,

The Endocrine Society, American Diabetes Association and the American Association of Clinical Endocrinologists worried that patients may be afraid to take Avandia.

'Patients should continue taking all currently prescribed medications unless instructed otherwise by their health care provider,' Dr. Robert Vigersky of the Endocrine Society said in a statement.

'Stopping diabetes medications can cause significant harm and result in higher levels of blood glucose that may cause severe short term health problems and could increase the risk of diabetes-related complications in the long term.'

Would not it make more sense to advise patients still on Avandia to consult with their doctors urgently about possible alternatives? Meanwhile, it does not seem irrational to be afraid of taking Avandia, given the increasing evidence about its harms, and increasing evidence that what we know about its harms may be an under-estimate.

So I wondered why these august medical societies seemed so unaffected about the doubts about Avandia's safety, and about the evidence offered to support its use that the latest news ought to generate. It turns out that all three of the medical societies get financial support from, -- wait for it --, GlaxoSmithKline.

The Endocrine Society lists GSK as one of its Corporate Liaison Board Members. The American Diabetes Association lists GSK as one of its Banting Circle Supporters, that is, those that give at least $1,000,000 a year. The American Association of Clinical Endocrinologists lists GSK as a member of its Corporate AACE Partnership. (I was not able to find out the total amount contributed by GSK to either the Endocrine Society or the AACE.)

So once again, the loudest voices in support of the product come from those used to, and perhaps dependent on financial support from its manufacturer. As a physician, I have been particularly disappointed that our medical societies, whose missions are ostensibly to support our professional values, seem to act more and more like marketers for the companies whose contributions, rather than members' dues increasingly support them.

The cycle keeps spinning.

For further thoughts on the latest in the Avandia case, see this post by Howard Brody on the Hooked: Ethics, Medicine and Pharma blog, and this by Alison Bass on the Alison Bass Blog.

We posted earlier this year about how documents produced on discovery and recently unsealed during litigation suggested how AstraZeneca handled clinical research data in the marketing of its atypical anti-psychotic drug Seroquel (quetiapine). A new crop of documents has just been released, providing yet more insights, as reported by the St Petersburg (Florida) Times:

Behind the scenes at the global pharmaceutical company AstraZeneca, the team in charge of the blockbuster antipsychotic Seroquel had one mission: make the multibillion-dollar seller even bigger.

To that end, internal company documents released Wednesday show how the British drugmaker hid unfavorable study results, promoted unapproved uses and even considered pitching the drug as less likely to lead to suicidal thinking than competitors'.

In particular,

Documents suggest Seroquel studies were repeatedly subordinated to commercial goals.

When a study in 2002 failed to show that Seroquel's sustained release formula was any more effective than a placebo in treating schizophrenia, orders from the top were to keep the results 'in strictest confidence.'

When a scientist in England wanted to study the weight gain in rats on Seroquel, AstraZeneca declined to fund the research, saying 'we could wind up with results that are not clearly advantageous.'

In one discussion, it was suggested that authors of potentially helpful research reports who raised too many questions, slowing publication, should be asked to step down.

A researcher who pressed for results of an unfavorable trial was rebuffed for weeks before being given 'three or four sentences describing high-level results.'

AstraZeneca marketers were jealous of what they saw as competitor Lilly's ability to cast questionable study results in a positive light. 'They (Lilly) are able to spin the same data in many different ways through an effective publications team,' according to a 2003 memo. 'Negative data usually remains well hidden.'

As Seroquel's sales soared, documents reflect an ongoing struggle between the safety and marketing teams over the potentially damaging issue of weight gain. In 2000, the company's scientists said data did not support the marketing claim that Seroquel resulted in only 'limited' weight gain. Close to 23 percent of the people who took the drug gained more than 7 percent.

Despite the safety team's objections, the word 'limited' remained on Seroquel's label for two more years.

This is a reminder how beleaguered we advocates of evidence-based health care (EBHC) have become. The idea of EBHC was that health care decisions for individual patients, and policies for groups of patients ought to be guided by critical review of the best available evidence from clinical research, guided by knowledge of biology and the biopsychosocial context of health, and informed by patients' values and preferences. The idea still makes sense to me, but it only works if physicians, patients and policy-makers have access to an unbiased sample of clinical research studies, so that studies with are not selectively suppressed to support vested interests. Although critical review can account for inevitable trade-offs, compromises, and errors in how studies are designed, implemented, and analyzed, the clinical epidemiological methods it uses are really not designed to root out falsehoods and deliberate deception.

However, the ongoing story of Seroquel, and many other cases discussed on Health Care Renewal suggest that when clinical research is sponsored by those who can profit from the product or service it evaluates, that research is prone to suppression and manipulation. Although I believe there are many honest scientists who work for pharmaceutical, biotechnology, device, health information technology and other health care corporations, it seems they often have to answer to marketers whose only goal is to sell more product.

As long as clinical research is sponsored and run by the people who can profit directly from selling the products and services the research is meant to evaluate, the ideal of evidence-based health care becomes less attainable.

As we have said before, suppression and manipulation of research amounts to post-hoc abuse of research subjects who volunteered their participation believing that it would advance science and health care.

Furthermore, suppression and manipulation of research can deceive physicians into prescribing tests and treatments that will fail to help, or even harm patients, and deceive patients into thinking that they are getting the best possible tests and treatments, when, again what they are getting is ineffective or even harmful.

In my humble opinion, there is an increasingly strong argument that clinical research should not be controlled, and probably should not be done at all by organizations with vested interests in the research producing results favorable to their products.

The parade of legal settlements marches on. The latest story is about Forest Laboratories and its marketing of Celexa (citalopram ) and Levothyroid (l-thyroxin). Here is the most complete version, courtesy of Natasha Singer reporting for the New York Times. First, the lead sentence:

A unit of Forest Laboratories, the maker of the antidepressant Celexa, agreed on Wednesday to pay more than $313 million to settle criminal and civil complaints, including a claim that it had illegally promoted the drug for use in children.

Here are the charges:

Among the criminal charges was one that the subsidiary, Forest Pharmaceuticals, marketed Celexa, which was approved only for adult depression, to treat children and adolescents. The government also claimed that, in conjunction with the company’s off-label promotion, Forest publicized the positive results of a study on Celexa in adolescents while failing to tell doctors about a similar study that had negative results.

'Forest Pharmaceuticals deliberately chose to pursue corporate profits over its obligations to the F.D.A. and the American public,' Carmen Ortiz, the United States attorney for the District of Massachusetts, said in a statement Wednesday.

In addition, federal prosecutors accused Forest of paying doctors to induce them to prescribe Celexa and another antidepressant, Lexapro. The remuneration included 'cash payments disguised as grants or consulting fees, expensive meals and lavish entertainment, and other valuable goods and services,' the government said in its civil complaint.

Among the items that Forest sales representatives gave to doctors from 1998 to 2005, the complaint said, were tickets to St. Louis Cardinal games, which were to be 'leveraged and sold as a reward for prescriptions'; a $1,000 gift certificate to Alain Ducasse, a gourmet French restaurant, for a high-prescribing child psychiatrist; a deep-sea fishing trip off Cape Cod for a doctor and his three sons; $400 in Broadway theater tickets for a doctor and his wife; and Red Sox tickets worth $2,276 to be used for doctors in the Boston area.

So we not just off-label marketing, but suppression of clinical research (of course, a study whose results were not favorable to the product being marketed), and payments to doctors as an "inducement to prescribe."

But wait, there is more:

As part of the criminal settlement, Forest Pharmaceuticals, which is based in St. Louis, agreed to plead guilty to one felony count of obstructing justice, acknowledging that employees had lied to F.D.A. officials during a plant inspection in 2003.

The company also agreed to plead guilty to two misdemeanors, one of which covers the company’s misbranding of Celexa by marketing the antidepressant for use in children from 1998 to 2002.

The other misdemeanor covers the illegal distribution from 2001 to 2003 of an unapproved drug, Levothroid, to treat a thyroid hormone deficiency. Such thyroid pills, made by various drug makers, had been sold in the United States since the 1950s without F.D.A. approval. But in 2001, the agency told drug makers that they needed to reduce their distribution of such medications until the companies obtained agency approval to market the pills.

The criminal charges accused Forest of making a deliberate decision to continue distributing the drug in quantities exceeding the F.D.A.’s directive. After the agency sent a warning letter to Forest, the company directed employees to work until 1 a.m. to continue shipping as much Levothroid as possible, according to the criminal complaint.

So there was also obstruction of justice in the form of lying to the FDA, and selling drugs that the FDA had ordered not to be sold.

So what are the penalties?

The criminal settlement calls for the company to pay a $150 million fine and to forfeit an additional $14 million in assets. Forest will also pay more than $88 million to the federal government and more than $60 million to the states to resolve a civil complaint that its actions caused false claims to be submitted to federal health care programs. In addition, two whistle-blowers will split $14 million from the federal share of the settlement.

Forest has also entered into a five-year corporate integrity agreement, requiring an independent expert to review the company’s compliance with drug marketing regulations.

So here we go again. A large drug company was up to no good, suppressing research, paying doctors for their prescriptions, lying to the FDA, and disobeying its orders.

The penalty seemed large, over $300 million. However, Celexa was a big revenue generator at the time the events above occurred, topping $1 billion in revenue first in 2002 (per Forbes here). Furthermore, as noted by Ed Silverman on Pharmalot, it seems no individual will suffer any negative consequences for authorizing, directing, or implementing the conduct described above. Finally, as best I can tell, despite the fact that a Forest subsidiary will plead guilty to a felony, the company is not going to be barred from doing business with the government.

So, despite pleading guilty to a felony and three misdemeanors, neither Forest as a company nor any individual working for the company will really suffer very much. On the other hand, the leaders of Forest have been doing very well. The company's CEO, Howard Solomon, was number 18 on Wall Street Journal list of the 25 highest paid CEOs over the last decade. His total realized compensation was over $385 million over the last 10 years. According to the company's 2010 proxy statement, his total compensation in 2009 was $8,267,236. The four other highest paid executives made from just over $2.5 million to $5.3 million.

So here we go again. Another large health care organization has been found to have done wrong, but the only penalty is a fine that whose impact will be diffused across the whole company, and ultimately be paid by its employees, its customers, including patients, and its stockholders. Meanwhile, the people who authorized, directed, or implemented the wrong doing apparently will pay nothing and receive no negative incentives. Furthermore, the top leaders of the company, whose huge compensation in the past was increased by the results of the wrong doing, will continue to prosper.

As we have said again and again, we will not deter unethical behavior by health care organizations until the people who authorize, direct or implement bad behavior fear some meaningfully negative consequences. Real health care reform needs to make health care leaders accountable, and especially accountable for the bad behavior that helped make them rich.

By the way, the current case offers an avenue for those who do not like what Forest did to ask those who are supposed to be ultimately responsible for its behavior how this was allowed to happen. The board of directors of the company is supposed to be ultimately accountable for the company's actions. As we have noted before, these directors are supposed to "demonstrate unyielding loyalty to the company's shareholders." [Per Monks RAG, Minow N. Corporate Governance, 3rd edition. Malden, MA: Blackwell Publishing, 2004. P.200.]

The current directors of Forest Laboratories, according to the company's 2010 proxy statement, include Dr Nesli Basgoz, "Associate Chief for Clinical Affairs, Division of Infectious Diseases, Massachusetts General Hospital (MGH)," and "Associate Professor of Medicine at Harvard Medical School." Also, it includes Dr Lester B Salans, "Clinical Professor" at Mount Sinai Medical School, not to mention Dr Peter J Zimetbaum, "Director of Clinical Cardiology" at Beth Israel Deaconess Medical Center in Boston (BIDMC), and "Associate Professor of Medicine at Harvard Medical School." Maybe some enterprising student journalist will get to ask the good doctors how they let things at Forest get so ethically out of hand.

With apologies to the late Frank Zappa... even though we are going through the dog days of summer, the parade of health care troubles in the news is never ending, so I thought I would recap some of the more interesting issues discussed by some of my fellow health care skeptic bloggers.

We have discussed the ongoing decline of primary care. On DB's Medical Rants, Dr Robert Centor takes on the topic: "The system has, without consciously meaning to, held primary care in contempt." The result is a "quiet rebellion: of primary doctors.

We have discussed whether the currently fashionable idea of "accountable care organizations" (ACOs) might turn out to be a cover for health care oligopolies. See what Paul Levy, CEO of the Beth Israel/ Deaconess Medical Center said about them in his blog, Running a Hospital.

We frequently talk about the manipulation or suppression of clinical research studies by those with vested interests in the results pointing in a particular direction. On the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody wondered why the FDA will not even reveal the identities of the clinical researchers who did the studies on which it based its decision to approve the Infuse bone growth enhancement device.

Prof Carl Elliott has done an outstanding job investigating commercially funded and implemented clinical research. Dr Brody reviewed his new book, White Coat, Black Hat. In the Carlat Psychiatry Blog, Dr Daniel Carlat reviewed Prof Elliott's new article in Mother Jones on how a pharmaceutical company sponsored drug trial went badly awry.

We asked whether the former CEO of a for-profit hospital chain who resigned after the company paid a > $1.7 billion penalty to settle charges of fraud would be a proper candidate to be governor of Florida. After Rick Scott won the Florida Republican primary, Maggie Maher, writing in the Health Beat blog, took on Scott's dubious past as prologue to a worrisome future.

Well I'm about to get sick
From watchin' my TV
Been checkin' out the news
Until my eyeballs fail to see
I mean to say that every day
Is just another rotten mess
And when it's gonna change, my friend
Is anybody's guess

So I'm watchin' and I'm waitin'
Hopin' for the best
Even think I'll go to prayin'
Every time I hear 'em sayin'
That there's no way to delay
That trouble comin' every day
No way to delay
That trouble comin' every day
- Frank Zappa

An editorial appeared in the latest edition of Nature Medicine that suggested "crusaders" are making much too much fuss over insignificant "competing financial interests." [Anonymous. A really serious conflict. Nature Medicine 2009; 15: 463-4]

The Editorial's Arguments

Instead of regarding all conflicts of interest as part of a "monolithic scourge," it suggested we should only attack them in two specific situations.

Bad Conflicts of Interest

The first is when it leads to falsification of research data:

If there is one reason we need to worry about CFIs [competing financial interests], it is because they could lead to misconduct whenever a researcher has a financial incentive to fabricate data. So, if a clinical trial goes ahead on the basis of fraudulent preclinical work or if a drug is approved on the basis of false clinical data, the problem is more profound than can be addressed by the declaration of a CFI. Researchers or clinicians who produce sham data to continue receiving funds from a company must be subject to severe disciplinary actions from their institutions and funding bodies.

The second is when it leads to withholding of data in certain circumstances:

Companies that conceal negative data from regulators to receive approval for their drug should face not only fines but also penalties as serious as criminal charges. In any case, the focus should move away from CFI declarations and toward exposing and punishing scientific misconduct.

Some Conflicts of Interest are Unavoidable

On the other hand, the editorial asserted that conflicts of interest are unavoidable in certain situations.

But even though a lot has been written about this subject, it is seldom acknowledged that not all CFIs are equally insidious and that some are even necessary for the success of translational research.

Scientists who share their expertise with a company and clinicians who agree to conduct a clinical trial have to be compensated for their work in the same way that every other professional ought to be rewarded for his or her labor. To suggest that they should make their contributions freely is disingenuous, and to argue that they should not get involved at all can only slow the development of new medicines.

Academic institutions and their employees must be free to benefit financially from the fruits of the advances made in their laboratories, either by independently developing them into products or by selling them to the highest bidder. In the US, the Bayh-Dole Act has protected this right for nearly three decades, and CFIs that result from a university's right to enact this policy should not raise eyebrows.

Bad Outcomes of the "Crusade" Against Conflicts of Interest

In addition, the editorial argued that because of excess attention paid to minor or unavoidable conflicts of interest, bad things may happen. Clinical trials would be discouraged.

However, the fact remains that clinical trials are very expensive, and only the pharmaceutical sector has both the incentive and the deep pockets to pay for them.

And innovation would be slowed.

A third issue that is rarely acknowledged is that the stridency with which the CFI crusaders fight financial interests has created a milieu in which pharmaceutical firms have increasingly less breathing space to conduct their business, leading to a further slowing of drug development.

Finally, the editorial exhorted:

Let us instead accept that most financial interests do not represent a conflict as a matter of course and that the influence of money is negative only if it leads to scientific fraud—the one infidel we need to burn at the crusader's stake.

Logical Fallacies and Inflammatory Rhetoric

It is discouraging to see such sloppy thinking and inflammatory rhetoric appear under the masthead of a prominent journal. How was the thinking sloppy? Let me count the ways, and explain the logical fallacies used by the editorial to support its contention.

Arguing that Conflicts are Unavoidable Using False Dilemmas and Appeals to Common Practice

The editorial suggests some conflicts of interest may be unavoidable, even necessary for the advancement of science. To do this, it provided a series of false dilemmas and appeals to common practice. A false dilemma is an argument that x and y are mutually exclusive, when they are not. An appeal to common practice is an argument that because something is common practice, it is necessary, moral, correct, or the only course possible.

The editorial argued that researchers would not work for free, implying that if drug and device companies could not pay researchers to perform clinical trials, no clinical trials would be done. This is a false dilemma, because it is based on the unstated assumption that there is no other possible source of payment for clinical trial researchers other than the companies whose products the trials evaluate. It may be true that it would be hard to get anyone to conduct clinical trials for free, but there is no law of nature that dictates that all clinical trials must be financed directly by companies whose products are the subjects of these trials, or that prevents clinical trials from being funded by government agencies and/or non-governmental organizations disinterested in whether the results favor one treatment or another. Such disinterested sponsors paying researchers would not create conflicts of interest.

The editorial argued that if academic institutions and their employees cannot benefit financially from "the fruits of the advances made in their laboratories," there would be no drug and device development. This is a false dilemma, because it is based on the unstated assumption that the only setting for drug and device development is academic institutions. There is no natural law, however, that restricts drug and device development to academic institutions, or prevents drug development to be done by drug and device companies, or by independent laboratories. The editorial also appended an appeal to common practice. Bayh-Dole may be the current law in the US, but it is hardly natural law.

The editorial argued that without the "deep pockets" of the "pharmaceutical sector" and device companies, no one would pay for clinical research. This was a repetition of the false dilemma noted above. There is no natural law that prevents government and non-governmental organizations from sponsoring clinical trials. The editorial again appended an appeal to common practice. Current laws and social conventions have made drug and device companies extremely profitable, but continuation of their profitability is hardly inevitable.

Red Herrings to Distract from Other Bad Effects of Conflicts

While the editorial identified two particularly bad kinds of conflicts of interest, it ignored other instances that could be equally bad. This was something of a red herring. Although the two examples of bad effects of conflicts of interest were undeniably important, they distracted from other bad effects which the editorial chose to ignore.

The editorial correctly identified falsification of data as bad, but ignored the entire catalog of ways in which clinical research studies can be manipulated to make them more likely to favor a sponsor's product. See our posts (here and here) and the links contained therein for multiple examples of such manipulation.

The editorial noted that concealing data from regulators in order to win drug approval is bad, but ignored all the instances in which data has been suppressed outside of the regulatory process to make drugs or devices seem more efficacious or less dangerous than they really are. See this link for some of our posts containing relevant examples. If it is bad to fool people who must make regulatory decisions, why is it not so bad to fool physicians and patients who must decide whether to use drugs or devices?

The editorial further ignored that conflicts that affect how research is conducted or reported may be linked to conflicts that affect how research is disseminated or used in decision making. The clinical researcher who is paid by a drug or device company to conduct a clinical trial may also be an academic physician paid by the same company as a consultant or through a speakers' bureau to give talks and presentations, and write review articles favorable to the company's product. If it would be bad for the researcher to falsify data to make the product look better, why would it be acceptable for the researcher to act as a huckster for the product while pretending to be a disinterested academic? See this link for posts discussing stealth marketing, and this one for posts discussing the use of key opinion leaders.

Ambiguity and Ad Hominem Attacks Inflating the Bad Effects of Fighting Conflicts

While the editorial minimized the bad outcomes of conflicts of interest, it resorted to ambiguity and inflammatory language to exaggerate what might happen were conflicts to be reduced.

Its most dire prediction of the results of reducing conflicts was that doing so would create a "milieu" in which "pharmaceutical firms have increasingly less breathing space." Literally, this statement was nonsense. Metaphorically, it did not make a clear argument that these highly profitable companies (and even more profitable device companies) could not survive in a "milieu" in which their products were tested by researchers which the companies could not influence. This was not clearly a logical fallacy, but just word-play presented a reasoned argument.

Given how prevalent political correctness is, repeatedly characterizing people concerned about conflicts of interest as "crusaders" is inflammatory indeed. Being called "pharmascolds" is one thing, but "crusader" in some circles is regarded as equivalent to racist, a nasty term to label those who promote the separation of clinical research and medical education from commercial interests. Thus, the editorial winds up with a rather nasty version of an ad hominem attack.

We have seen numerous examples of the use of logical fallacies in defense of conflicts of interest, often by authors who were themselves conflicted. It is especially sad to see the editors of a scholarly medical journal employ such logical fallacies in the defense of conflicts of interest.

ADDENDUM (11 May, 2009) - See also the comments by Dr Doug Bremner in the Before You Take That Pill Blog.

ADDENDUM (20 May, 2009) - For an example of how the term "crusader" has become politically incorrect in the US context, see this article in the Boston Globe.