Again, Defending Conflicts of Interest with Logical Fallacies

The latest version of the argument that we are all getting too worked up over conflicts of interest in health care has appeared, this time in a scholarly, peer-reviewed journal. (Hirsch LJ. Conflicts of interest, authorship, and disclosures in industry-related scientific publishing: the tort bar and editorial oversight in medical journals. Mayo Clinic Proc 2009; 84: 811-821. Link here.) The major point of the paper seems to be that payments to physicians, particularly academic physicians by pharmaceutical, biotechnology, and device companies are necessary for medical progress, so instead of perseverating about them, we all should pay far more attention to the evil of payments made for expert testimony by physicians who serve as expert witnesses in litigation against such companies.

In the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody addressed this main argument, while dismissing the bulk of the article as merely "illogic and innuendo." I think that Dr Brody failed to grasp the educational opportunities that the Hirsch article presented. It offers a true cornucopia of logical fallacies, making it ideal teaching material for the sort of course in logic and evidence that should be taught in all our medical schools, but is not.

So let me use this "teachable moment" to address just some of the many logical fallacies that Dr Hirsch so enthusiastically employed, in order of their first appearance in his article.

Appeal to Ridicule

There is a politically correct herd mentality that ascribes to the concept that objectivity is forsaken by medical companies that seek profit (and by their employees) because of 'conflict of interest.'

Also,

These overt restrictions on researcher communications in today’s climate of political correctness on COI are causing more than policy debates among various stakeholders....

In both these examples, concerns about conflicts of interest are deemed mere "political correctness." Thus, this is an appeal to ridicule.

Yet today there is a McCarthyesque reaction to the term, conflict of interest, with an unstated presumption of guilt until proven innocent.

Here instead the term of ridicule is "McCarthyesque."

Straw Man Fallacy

There is a politically correct herd mentality that ascribes to the concept that objectivity is forsaken by medical companies that seek profit (and by their employees) because of 'conflict of interest.'

This single sentence employed two fallacies for the price of one. I would challenge Dr Hirsch to provide a credible example that any thoughtful figure in the conflict of interest discussion has dismissed the objectivity of all for profit health care corporations, and all of their employees. He apparently has constructed a straw man argument which he has attributed to his opponents, one that is either to strike down than their real arguments.

Appeal to Authority

Previously, the president of the Association of American Medical Colleges emphasized that the term indicates a state of affairs and not a behavior, that COIs are ubiquitous, and that despite their inaccurate portrayal by the media, COIs do not indicate the occurrence of any improper behavior, much less scientific misconduct, analogous to a state of potential energy

If he said it, was he right? Is he still right today? Obviously, because someone with a distinguished title expresses an opinion does not mean it is true. Thus, this is an appeal to authority. (Note: since the reference appended to this sentence appears to have nothing to do with the content of the sentence, it is not even clear that the authority in question made such a statement. Link here.)

Appeal to Common Practice

Publication bias (preferential publication of studies with positive outcomes vs trials with negative, neutral, or ambiguous outcomes) has been reported for more than 2 decades,....

Publication bias clearly extends to government- and nonprofit-funded research....

The thrust here was clearly that publication bias is common and has been around for a long time, so why worry? This is an appeal to common practice, which equates a statement that a pheonomenon is common with the assertion that it is reasonable, justified, ethical, optimal, etc.

Special Pleading

For the 2008 article that was critical of Merck’s authorship practices by Ross, Hill, Egilman and Krumholz, the entire disclosure statement was, 'All of the authors have been compensated for their work as consultants at the request of plaintiffs in litigation against Merck & Co, Inc, related to rofecoxib.' Only in the middle of the Comment (Discussion) portion of the article was it mentioned that the authors had served as paid expert witnesses for plaintiffs’ attorneys in rofecoxib litigation. The terse disclosure statement seems at odds with JAMA’s stated policy in its Instructions for Authors that financial COI disclosure must be complete. Regardless, the information provided hardly conveyed that, as of January 2007, Krumholz had received more than $300,000 for his consulting from plaintiffs’ attorney Mark Lanier (no relationship to Mayo Clinic Proceedings Editor-in-Chief William L. Lanier, MD), which only became public in a letter to the editor of BMJ that responded to a previous article critical of Merck by Krumholz et al.

Krumholz’ remuneration seems substantial until it is compared to that of another coauthor of the JAMA authorship report,16 David Egilman. Egilman has testified for Mr Lanier and other attorneys in more than 100 tort cases (nearly always for plaintiffs) for approximately 2 decades and, by his own estimate, has earned $20 to $25 million for such testimony.

[Note: this discussion appeared in the midst of a long tirade against the editorial policies and practices of JAMA, especially in relation to controversy about the drug rofecoxib (Vioxx), the now withdrawn Merck Cox-2 inhibitor. Dr Hirsch apparently was responsible for Merck's publication policies about this drug. Further note that there are major questions about whether the figures supplied by Dr Hirsch are correct. Appended to the post in Dr Brody's blog post is a categorical denial by Dr Krumholz that he was paid, as asserted by Dr Hirsch, over $300,000, and evidence against the assertions by Dr Hirsch about Dr Egilman's pay.]

While Dr Hirsch alleged that the disclosures by the authors of this article were incomplete, he did not compare them to the disclosures made by authors of other articles in JAMA. In fact, I have never seen an article in JAMA which included disclsoure of dollar amounts, and could not find any such disclosure in spot checks of the latest issue.

On the other hand, here is the disclosure Dr Hirsch made in his own article:

Dr Hirsch was an employee at Merck & Co from 1988-2006 and managed the Medical Communications Department for clinical research publications from late 2001 to mid-2006. He currently is employed at a medical device and technology company that has no financial interest in any matters related to rofecoxib or the resulting tort litigation involving Merck & Co. Dr Hirsch owns mutual funds with stock from a variety of pharmaceutical and device companies, including Merck, and some shares of Merck and other medical product companies.

He did not disclose dollar amounts connected with any of these activities. He would not name his current employer on the grounds that it has no interest in rofecoxib and related litigation. However, his article is ostensibly about the broader issues of conflict of interest, authorship, etc which may relate to the interests of Becton Dickinson, which currently employs Dr Hirsch in the capacity of Worldwide Vice President of Medical Affairs, BD Diabetes Care. He did not name the "medical product companies" whose shares he owns.

Thus, Dr Hirsch argued that Dr Krumholz and Dr Egilman were wrong not to disclose the details of their financial arrangements with plaintiffs' attorneys (setting aside the likely inaccuracy of Dr Hirsch's contentions about the specifics of these arrangements), even though the detail they provided in their disclosures was similar to that provided by other JAMA authors, and even though Dr Hirsch did not find it necessary to himself disclose in such detail. Thus, Dr Hirsch was advocating a double standard, and in this case, his argument amounts to a special pleading, since the standard he advocated for others was not the same he felt obliged to uphold.


Appeal to Fear

[standards regarding COI] are beginning to affect the willingness of prominent researchers to interact with industry in any manner that involves even minimal compensation for their time and efforts.

Also,

There are serious negative implications for the future of medical product development if top academic researchers are shamed into ceasing any type of compensated interactions with industry.

Dr Hirsch implied that medical progress would be greatly endangered if industry no longer paid practicing physicians and full-time academics to work on the side, and that such payments would no longer be possible were COI disclosure requirements to be made more strict. Such dire warnings, without evidence to support them, amount to appeals to fear.

Summary

So Dr Hirsch has provided yet another example of an apologia for conflicted physicians and academics based on a panoply of logical fallacies. We have offered several other examples of fallacious defenses of conflicts of interest, compiled here.

It is sad to see logical fallacies so cavalierly employed. There frequent, sometimes strident use in current health policy suggest the need to better train health care professionals in logic and the use of evidence.

I am still awaiting a defense of the sorts of conflicts of interest that we frequently discuss on Health Care Renewal that is based on logic and evidence, but it may be that no one can produce such a defense.

Meanwhile, we continue to recommend that at the very least, medical academics, medical academic institutions, and other health care not-for-profits or NGOs should reveal in detail what payments they get from companies selling health care products or services, and how these payments could relate to the companies' marketing or lobbying efforts. In the US, some such disclosure would be mandated by the proposed "Sunshine" legislation now being considered by the US Congress. (By the way, note that this problem is hardly confined to the US, and needs global, not just American attention.)

However, physicians (at least physicians in full-time private practice, academic positions, and employed by mission-oriented not for profit organizations) should go further, and consider whether receiving industry money is worth the ongoing damage it does to our professionalism and our professional reputations. Medical schools, universities, health care foundations, disease advocacy groups, and other health care not-for-profits and NGOs should also go further, and consider whether receiving industry money is worth the ongoing damage it does to their missions, and their institutional reputations.

Pfizer's Pfantastic Pfine: My New Strategy to Secure a Piece of the Pie

In today's Philadelphia Inquirer in a story entitled "FDA: Pfizer ignored warnings, gets record fine" we learn that:

The [$2.3 billion] fine, which had been expected, was the largest ever paid by a drug company for defrauding the government's Medicare and Medicaid programs.

The U.S. Justice Department said that it included the largest criminal fine in U.S. history - $1.2 billion.

Authorities called Pfizer a repeat offender, noting this is the fourth such settlement of government charges in the last decade. The government said it would monitor the company's conduct for the next five years to rein in the abuses.

I have noted a near impossibility in securing interviews from pharma, Pfizer and Wyeth included, for many years. Perhaps I've taken the wrong tack. My CV emphasizes critical thinking, integrity, and expertise in biomedical data and terminological issues that help achieve clarity in research information analysis and dissemination.

Perhaps I need to try a new style.

Here is a proposed new introduction:

Yale-trained Medical informatics specialist with experience in pharma. Creative in thought and application to the point where I can spin anything to the liking of senior management. Will utilize Yale education to the fullest in misusing research funds in providing generous compensation to friendly physician advocates for company drugs and for compensating ghostwriters. Will employ skills in data modeling and medical decision making to conceal negative research results and put a pretty veneer on even the worst debacles for marketing purposes. Will hire the finest generalist staff from McDonald's and supply them with a Process Manual in adverse events detection and reporting, to minimize the chances of problems being discovered prior to major profits being generated. Will utilize creativity to simply make stuff up about new uses for drugs. Finally, will ensure only the tastiest of rotisserie chicken and sides in company cafeteria to improve corporate morale during layoffs as a result of upcoming merger.

I wonder how that will pfly, er, fly.

-- SS

Pfizer's $2,300,000,000 Settlement No Longer Anechoic

Re the $2.3 billion dollar Pfizer settlement, in the headlines today...

Health Care Renewal readers learned about it in February, here.

At the time, we mentioned how little coverage the news had received, a manifestation of the anechoic effect.

We said this about it then:

We have posted about numerous settlements of charges of misbehavior by drug, device, insurance and other health care organizations. Stacking them all up suggests the magnitude of bad behavior by the leaders of health care organizations. Yet it's not clear that all these monetary penalties are discouraging bad behavior.

In almost all cases, the monetary penalties accrue to the organization as a whole, not to the individuals whose behavior incited the settlement. And I have not so far ever heard of a case in which the organization which has to pay a settlement turns around and enforces a penalty upon the responsible leaders. Thus, the deterrent effect, even of large penalties, is thus diffuse. An executive, knowing that bad behavior may increase short term profits, and hence may markedly increase his or her compensation in the short run, may be undeterred by the threat of a future settlement that he or she does not have to pay. Instead, the settlement may come out of the pockets of stock-holders, employees as a whole, customers, clients, or patients, or the public.

If we want to prevent health care leaders from continuing "childish" behaviors, allowing health care to "spin out of control," (as per President Obama' inaugural address, see post here), we must do a better job of enforcing negative consequences, as the mother of any five-year old will tell us.

Rest assured we will have more to say about this topic, now that it is in the headlines.

A New Perspective on Evaluating the Effects of Financial Conflicts of Interest on Research

I just posted about an article from the August issue of the Journal of Epidemiology and Community Health (link here, requires subscription.) Health Care Renewal readers may want to peruse this issue, which has some very interesting articles on conflicts of interest and related issues in research.

In particular, an article by Prof Sander Greenland offers a fresh discussion based on perspectives from epidemiology, statistics, and cognitive psychology of the effects of financial conflicts of interest (COI) on (clinical, epidemiological, and health services) research (Greenland S. Accounting for uncertainty about investigator bias: disclosure is informative. J Epidemiol Community Health 2009; 63: 593-598. Link here, requires subscription.)

Since only subscribers can easily get this article, and because of its importance, let me summarize its main points and provide appropriate quotations.

Financial COI as Causing One Type of Investigator Bias

Greenland views financial conflicts of interest as a source of one kind of investigator bias, defined as "the biasing of study results towards results expected or desired a priori by the investigators." He believes that this is a particularly important kind of bias, "the pool of reported study results may be affected seriously by prejudices and vested interests of investigators and sponsors. Such incidents suggest that investigator bias can be larger than any other bias, and may often encourage adoption of dubious or even deadly treatments."

Focus on Effects of the Bias, Rather than Intent

Greenland posited that the issue here is not intent,

Investigator bias may be intentional or subconscious, may be of venal or noble origin, and may manifest in outright fraud or in subtle fallacies held true by the investigator. It may reflect no more than the influence of sincere wishes or beliefs of the investigator or their research community on the way findings are interpreted, or it may represent premeditated attempts to mislead.

The danger is that raising the issue of intent may lead to emotional arguments rather than sober thinking about what effect conflicts of interest should have on interpreting study results,

here we encounter an emotional minefield of indignation driven by fears of prejudice in and abuse of such priors [that is, beliefs about the effects of investigator bias due to conflicts of interest.] Similar objections meet proposals to down-weight studies that produce results favourable to sponsors or other parties with financial ties to the investigators.

Rather, the issue is that conflicts of interest may indicate a high risk that a study is biased, and obviously, biased in a certain direction, "we expect investigator bias, if present, to fall in the direction favouring their or their sponsor’s financial interest."

An Approach to Evaluating the Effects of Investigator Bias due to Financial COIs

Greenland pointed out that it may be difficult to account for the effects of investigator bias due to COIs by just being careful in the evaluation of the report of a given research study, "incomplete documentation of ad hoc design and analysis decisions makes investigator bias especially difficult to detect and deal with." Furthermore, "one cannot detect unreported biasing judgements without having the data and the time to reanalyse it."

Thus, the challenge is to get accurate information about COIs, and then use it to accurately evaluate a particular study. The realities of life in the often conflicted world of medical academia means that conflicts of interest may generate a large amount of bias. Greenland suggested that this

reflects a harsh reality. In research funded or conducted by parties with a direct financial stake in the results, there may be an implicit threat of funding withdrawal (or worse) if results presented do not favour the sponsor’s interest or conform to their perceived needs for marketing and litigation.

Furthermore, he noted,

Sponsored investigators have been sued by their corporate sponsors in efforts to block publication of undesirable results. Investigators with no corporate ties have faced interference from corporations upset with their findings. Not all investigators choose to fight such pressure, which leaves them the option to either not publish unfavourable results or else not produce such results. Some go so far as to guarantee their sponsor that the results of their proposed study will be helpful.10 Meanwhile, unfavourable results from research conducted within a company may languish as in-house memos that can be obtained only via litigation, and then only if the court orders their release.

However, information provided about COIs may not be complete or accurate.

Once we accept the reality that disclosure data contain relevant statistical information, we can turn to the quality of information ascertainable from available reports.

There are reports of investigators disclosing only a small fraction of their financial support from industry, even when required to give a full account by university and granting-agency rules. There is little reason to expect more thorough disclosure in journal articles. Full disclosure is often evaded via technicalities, such as payment of non-descript consulting fees that are not explicitly earmarked for the article and thus not deemed reportable, even when they may be for time spent on the database from which the article is generated. If reported at all, such funds may be described only by phrasing such as 'author X has served as a consultant (or expert) for company Y', not that the payments for such services were made with the understanding that they would support time spent on the study being reported.

The frequency of under-reporting and deceptive reporting is far from known. Most incidents come to light only when investigation or litigation occurs, and those discoveries are not always reported in public venues. Other devices for undermining disclosure requirements include funds channelled through innocuously titled foundations or institutes set up specifically to conceal the ultimate funding source. Detecting such events and devices may demand investigative effort beyond the resources of almost all readers.

However, while there may be considerable false negative information about COIs, false positive are unlikely, "In contrast, it is hard to imagine that many articles report funding from a financial stakeholder when in fact there was none, so that misreporting may be limited to under-reporting."

Conclusions and Future Directions

Greenland concluded that investigator bias is very important.

Investigator bias has the potential to overwhelm all other biases. It can become the dominant force in contexts (such as expert reports and testimony for litigation) in which the restraints imposed by editors and peer review are absent. Thus, because of its importance, investigator bias should not be dismissed as unapproachable, any more than we should give up research on what seem to be hopelessly mysterious diseases.

He reminded us that not all investigator bias is due to financial COIs, although that should not be used to deny the importance of bias due to financial COIs,

Although I have focused on distortion from financial input, I have no doubt that ideological commitment can be just as distortive. Indeed, dealing with ideological and other psychological sources of bias (such as commitment to earlier methods and conclusions) deserves to be on the research agenda for bias analysis.

He suggested some directions for the future,

In approaching these problems scientifically, I suspect aid will be needed from those branches of psychology that deal with distorted thinking among normal individuals and groups.

Openness of journals to unpopular research and strenuous debate remains the primary line of defence against information abuse and distortion. Such openness is not universal, and thus it seems likely that proposals to deal with investigator bias will raise a hornet’s nest of objections and questions. Perhaps the essential first step (if not major hurdle) is getting used to the idea that there may be good arguments for including the possibility of investigator bias in an uncertainty assessment. The demand for thorough financial disclosure may then seem no different from demanding hard ('objective') details of design and analysis to aid assessments. Like other psychological constructs, ideological biases will be far more difficult to evaluate but may nonetheless have hard correlates that signal their presence if not magnitude, such as attempts to suppress or boycott opposing views.

I highly recommend that those with access to this journal read Prof Greenland's article in full, and see the other related articles in this issue. In particular, Prof Greenland's article, and the article from the German chapter of Transparency International provide some clear thinking as a counter to the illogic that is now appearing as the backlash by the conflicted against the "pharmascolds" intensifies.

Fighting Corruption in Health Care - Suggestions from Transparency International

The August issue of the Journal of Epidemiology and Community Health featured a number of articles on conflicts of interest (COI) and medical and public health education and research. One notable contribution included authors from the German chapter of Transparency International (Spelsberg A, Martiny A, Schoenhoefer PS. Is disclosure of potential conflicts of interest in medicine and public health sufficient to increase transparency and decrease corruption. J Epidemiol Community Health 2009; 63: 603-605. Link here, requires subscription.) Transparency International is a major international NGO respected for its stand against corruption, and for transparency and integrity.

The article's major premises deserve quotation:

When Transparency International was founded in 1993, the focus for fighting corruption was mainly on bribes and corruption of civil servants in developing countries. While our definition of corruption was broad from the beginning, that is abuse of power or of a powerful position for personal advantage or benefit, the concept of preventing corruption had to be adjusted more recently.

conflicts between private and professionally consigned interests—be it in public office or in the private sector—create susceptibility to corruption....

Conflicts of interests are now considered as a major gateway for corruption in medicine and public health.They predominantly affect the way that doctors evaluate and use the products of the pharmaceutical and medical device industry by a systematic and ubiquitous exposure during professional life, starting at medical school.

Independent clinical research which can produce reliable results on new drugs or new medical technology has almost vanished and has been progressively replaced by industry-sponsored studies which are dominated by marketing interest of the manufacturers, including misleading selection or extensive falsification of data and results. Consequently, evidence-based guidelines or practice guidance often can no longer be assumed to be unbiased and free of conflicts of interests. Meta-analyses are at risk of being seriously distorted, even after adjusting for publication bias, due to inaccessible, unpublished data on clinical trials or inappropriate, for example non-reproducible, inclusion of such data....

Nowadays, medical expert committees are obliged to disclose conflicts of interests. Nevertheless, rarely is any action taken to control or to exclude advisers or experts with conflicts of interest since the extensive ties to industry of panel members have become the norm. It is therefore illusory to expect that disclosure alone without sanctions will be sufficient to increase transparency and decrease corruption in medicine and public health. Even if adequate sanctions follow, individual professional behaviour may not suffice for reversing the detrimental dependency of the medical and scientific community on industry. By the same token, corporate responsibility endeavours of drug and medical device companies should not remain voluntary efforts without tangible sanctions.

Let me quote below their major recommendations, edited just a bit:

Individual level

Professional codes of conduct for physicians and other health professionals, individual drug and medical device companies, health maintenance organisations, sickness funds, research organisations, etc. The common denominator of such codices consists of the ban of offering/accepting any personal gifts, including food and travel.


Organisational level within the medical system

Codes of conduct for academic medical centres, medical associations, patient and consumer organisations, organisations of healthcare professionals and producers of pharmaceuticals and medical devices. Each institution or organisation in healthcare as well as each professional in these institutions or organisations should be obliged to make any payments, honoraria or other benefits by pharmaceutical or medical device companies transparent.

Public registry of all clinical trials and other research activities involving patients, including post-marketing and pharmacovigilance studies. Publication of all relevant outcomes and results including null results, adverse effects and stopping rules, administrated and monitored by an independent institution such as the National Institutes of Health. Full disclosure of funding agencies, companies and responsible data centres.

Education of healthcare professionals including continuous medical education must be disentangled from commercial interests. The healthcare professional organisations should integrate graduate and continuing medical education in their codes of conduct.

Political level

Drug and medical device approval legislation: necessary prerequisites for starting drug approval process should include a complete and consistent disclosure (including amount) of beneficiaries of involved institutions, experts and organisations.

Implementing an expert anti-corruption agency for health at the national level authorised to take legal action. This includes activities in prosecuting conflicts of interest among health professionals and their institution, since such conflicts often result in rising healthcare expenditures without benefit for the public.
Society level

Monitoring of influence of commercial interests on public health and outcomes of medical interventions: annual reports to the public on health indicators and international comparisons including healthcare expenditures, estimated losses due to corruption and fraud in healthcare and recaptured resources by anti-fraud and anti-corruption measures.

Health Care Renewal readers may find it a useful exercise to compare these recommendations with their local situation. As far as I can tell, here in the US, almost none of these recommendations now obtain. Going through the list:

Individual level - In the US, codes of conduct promulgated by most medical societies do not completely ban accepting gifts. Not all drug and device companies, health maintenance organizations, insurance companies (the equivalent of sickness funds here), and research organizations have visible codes of conduct, and those that exist do not completely ban accepting or giving gifts.

Organizational level - Not all academic medical centers, medical associations, patient and consumer organizations, organizations of health care professionals, and drug and device companies have visible codes of conduct, and those that exist hardly make all payments, honoraria and other benefits completely transparent.

- There is a clinical trials registry. I am not sure if it includes post-marketing and pharmacovigilance trials (readers may be able to help me here). I do not know of any independent institution that monitors in detail the publication of all study results.

- US education, including continuing education of health care professionals is considerably entangled with commercial interests. Codes of conduct relevant to the relationships among industry and education are weak.

Political level - Drug and device regulation does not require complete and consistent disclosure of payments to medical schools, medical centers, and other research organizations which implement relevant research.

- There is nothing resembling an expert anti-corruption agency for health at a national level. Nor do such agencies exist at the US state level.

Society level - There is no systematic ongoing monitoring of commercial influence on public health and outcomes of medical intervention. There are no national reports that cover fraud and corruption and health care.

So as best as I can tell, here in the US, we currently are following almost none of these recommendations.

Maybe in other countries things are a little better. It would be interesting to hear from readers around the globe about this.

As I have repeated again and again, I believe true US health care reform requires improved transparency, and mechanisms to improve integrity and ethics like those suggested by these Transparency International authors.