Professional Integrity for Sale? “Sure,” Says Medscape!

Some chiropractors also practice homeopathy. According to Frank King, D.C., many more should be doing just that:

Homeopathy is an energetic form of natural medicine that corrects nerve interferences, absent nerve reflexes, and pathological nerve response patterns that the chiropractic adjustment alone does not correct. The appropriate homeopathic remedies will eliminate aberrant nerve reflexes and pathological nerve responses which cause recurrent subluxation complexes.

Not only does homeopathy correct nerve interferences, it empowers the doctor of chiropractic to reach the entire nervous system. What this means is that we can now better affect the whole person, and all of the maladies that affect us. Homeopathy’s energetic approach reaches deep within the nervous system, correcting nerve interferences where the hands of chiropractic alone cannot reach. Homeopathy is the missing link that enables the chiropractor to truly affect the whole nervous system!

But that’s not all:

Financial Rewards

Homeopathy means a multiple increase in business. Personally, I have been able to see and effectively help more patients in less time. The additional cash flow from broadening your scope of practice, increasing your patient volume and selling the homeopathic remedies is a wonderful adjunct. Better yet are the secondary financial benefits:

• Homeopathy is like an extension of you that the patient can take with them to apply throughout each day in between visits. The actual therapeutic benefits of homeopathy along with the inner comforts of the patient as they connect you with each dose they take.
• The dynamic broadening of your effective scope of practice multiplies the number of patients you can help and the multiple problems that each patient usually has. As you correct one set of problems, there are commonly other problems most patients don’t even tell their chiropractors. This doesn’t have to be the case anymore. Homeopathy empowers the chiropractor to correct conditions ranging from allergies to warts with incredible effectiveness!
• Obviously, the rule of multiples will exponentially increase when a homeopathic procedure is properly implemented into your practice. Many of the conditions people are suffering with have no viable solution without the dynamic duo of chiropractic and homeopathy.
  

You can be the doctor people will seek out, travel long distances to see, and pay cash for your valuable services. Take it from someone who has experienced it first hand, it’s a great position to be in.

This is no surprise. Most chiropractors relinquished whatever ethical integrity they might have had when they bought into the “subluxation” myth, and the field as a whole has a fine tradition of “practice building.”

Naturopaths, likewise, don’t mind winking at practice ethics in order to make an extra buck. Nor do MD quacks, of course. Hey, it’s getting harder and harder to make a living just by slogging through the morass of needy patients, onerous third-party billing requirements, diminishing payments, increasingly cumbersome practice guidelines, next-to-impossible-to-keep-up-with (nothing to say of tedious and technical!) medical literature, and all the rest. Why not sprinkle your practice with a little ‘diagnostic’ sugar that will appease those clingy patients—for a while, anyway—and that you won’t have to find billing codes for (because there aren’t any)? Heck, why not check out this offering from “bio-pro, inc. Amazing Anti-Aging Solutions (Healthier Patients, More Patients)”:

HOWW TOOOO ….

The “must do” seminars for those who own or are managing a Complimentary [sic]Medicine Practice.

Three day course teaches you:

How to relate to the patient, evaluate, test and diagnose

How to use solutions, mixtures, methods, supplies and equipment

How to protocol administration for Chelation, Oxidation, Chelox, TriOx, Ascorbates, UVBI

How to design and organize your office

How to hire and fire staff and to computerize

How to use public relations and marketing

How to manage compliance with Medicare, State Medical Boards and governmental regulatory agencies

Manuals included…

Each attendee receives one set of training materials, including:

Protocol Manual

Physicians Manual

Office Procedure Manual

Forms Book

Marketing Manual

Patient Results Manual

Employee Manual

Audio tapes

and other related material.

Bio-pro was founded in 1978 by the late Charles H. Farr, MD, PhD, the self-styled “father of oxidative medicine,” who was also a founder of the American College for Advancement in Medicine, the Mother of All Pseudomedical Pseudoprofessional Organizations (PPO). But none of this is surprising, right? After all, quacks quack.

What may have come as a surprise to beleaguered physicians who still play by the rules was this offering, just a few days ago, from Medscape Business of Medicine:

Six Ways to Earn Extra Income From Medical
Activities

You’re chasing after claims but watching reimbursement sink.

It’s a common story, and primary care doctors and even specialists are keeping their ears to the ground for other ways to boost their bottom line. Luckily, doctors have some fairly lucrative options that can help them maintain their income — and perhaps even increase it.

We looked at 6 avenues that physicians have taken to earn extra revenue. None of these activities require a tremendous amount of time. Participating in just 1 or 2 activities can put enough money in your pocket to allow you to breathe a little easier when the bills come in.

So what are those ‘6 avenues’? Let’s see:

• Work with Attorneys
• See Nursing Home Patients
• Serve as a Medical Director
  

So far, so not necessarily bad…

• Team Up with Pharmaceutical Companies
  

What??! Team up with pharmaceutical companies? Couldn’t that mean, like, just doing legitimate research and trying like hell to do it right? Uh, nope:

Drug and device companies spend billions of dollars each year to discover and promote new medicines and treatments, and they rely heavily on doctors to participate in these endeavors whether through clinical trials or serving as a speaker or consultant. It’s not uncommon for physicians to earn a minimum of 5 figures a year either speaking or doing clinical studies within their medical practice. Some doctors make in excess of $100,000 annually — on top of their income from seeing patients.

O’course, you gotta watch out for those pesky ethics killjoys, warns Medscape:

Although some extra money is nice, too much can turn heads — and not in a good way. In late January, The Boston Globe reported on an allergy and asthma specialist who was issued an ultimatum by his hospital, the prestigious Brigham and Women’s Hospital (Boston, Massachusetts): Stop moonlighting on behalf of pharmaceutical companies or resign from your staff position.

What it all comes down to is this:

Pros: With typical payments running about $1500-$2500 for a single talk, there’s substantial opportunity to supplement your regular income…

Cons: These arrangements are coming under increasing scrutiny from hospitals, legislators, regulators, and the media. In fact, some of the doctors whom we contacted for this article declined to talk about their involvement with drug companies.

Uh, no kiddin’. Funny that the “increasing scrutiny” doesn’t seem to come from organized medicine, medical schools, mainstream medical journals, state medical boards, or doctors in general. A couple of years ago I lamented the publication of a couple of book reviews, in the lofty New England Journal of Medicine, that celebrated trendy pseudomedicine. Shortly thereafter I received this from an emeritus editor:

I think the incursion into the bastions of medicine has to do with the fact that everything nowadays—absolutely everything—has become a market. If quackery appeals to the readers of the NEJM, it will be there. ”Is it true?” is no longer the question anyone asks, but “Will it sell?” And I think that applies to the editors of most major journals, as well.

True, dat. As for Medscape, this isn’t its first ethical gaff, and I agree with Bernard Carroll that it seems to have “a right hand – left hand problem.”

Oh yeah: what were the other 2 “avenues”? Those would be:

• Become a Media Personality
• Consult for Wall Street

Post Title → Professional Integrity for Sale? “Sure,” Says Medscape!

The Editorial that Wasn't: Evidence for Systematic Research Manipulation Undetectable by Critical Review

Woe to those of us who have been advocates for evidence-based medicine.  A short description of the evidence-based medicine is medicine whose practice is informed by critical, rigorous review of the best available evidence from clinical research as revealed by systematic search of the published research literature, as well as by the clinician's understanding of biology and the medical and biopsychosocial context, and by the patient's own values.

Evidence-based medicine is based on some key assumptions.  One is that a systematic review will reveal all the results of research studies that are relevant to the issue at hand.  A second is that while the research studies may be flawed and imperfect, they are reported honestly.

Unfortunately, as we have repeatedly discussed, there is more and more evidence that a systematic review will not reveal all relevant results, because research studies may be suppressed, perhaps often, when their results are unfavorable to vested interests.  (Look here for further discussion.)  There is also considerable anecdotal evidence that the design, implementation, and analysis of research studies may be manipulated to make the results more likely to favor vested interests.  (Look here for further discussion.)

An article by Vedula et al just published in the renowned New England Journal of Medicine suggests that such manipulation might be systemic, and that the reporting of manipulated studies may not clearly show what manipulation was done. (1)

To summarize, the authors got access through legal proceedings to internal study protocols and research reports from clinical trials sponsored by Parke-Davis (later merged into Pfizer Inc) of gabapentin (Neurontin) for a variety of clinical problems other than seizures.  Gabapentin was originally marketed as an anti-seizure drug, but Pfizer later "admitted guilt for off-label marketing."  (We discussed the stealth marketing campaign for Neurontin here.)  Vedula et al compared the primary outcome variables specified in the original research protocols, internal research reports, and any publications of the trials' results.  They identified 21 trials, 13 of which were published.  For 12 of the 13, the authors had access to the internal protocol, report, or both.  The main results were:

For 8 of the 12 published trials, there was a disagreement between the definition of the primary outcome in the protocol and that in the published report.... Sources of disagreement included the introduction of an entirely new primary outcome in the published report (in the case of 6 trials); failure to distinguish between primary and secondary outcomes in the published report, even though the protocol did distinguish between them (2 trials); relegation of a primary outcome in the protocol to a secondary outcome in the published report (2 trials); and failure to include in the published report one or more primary outcomes specified in the protocol (5 trials).

Furthermore, it appeared that failure of published articles to clearly and fully report results in terms of the original, pre-specified primary outcome variables occurred when these comparisons were not favorable to gabapentin. As the authors summarized:

Thus, trials with findings that were not statistically significant (P≥0.05) for the protocol-defined primary outcome, according to the internal documents, either were not published in full or were published with a changed primary outcome.

As shown in Figure 3, all the changes that took place between what was specified in the protocol, what was known before publication (as presented in the internal company research reports), and what was reported to the public led to a more favorable presentation in the medical literature of gabapentin's efficacy for unapproved indications.

They concluded:

We are concerned that the reporting practices observed in our analysis do not meet the ethical standards for clinical research or maintain the integrity of scientific knowledge. Fair and honest treatment of patients enrolled in clinical trials of any kind requires full, open, and unbiased reporting. Journal publication, a formalized platform for scientific discourse and dissemination of knowledge, should not be used as a marketing tool for off-label drug use.

Reporting biases such as those we describe here increase the likelihood that interventions will appear to be effective when they are not. Such biases can lead to the omission of negative findings in systematic reviews of intervention effectiveness and in evidence-based guidelines. For example, the 2005 Cochrane systematic review regarding the effectiveness of gabapentin for acute and chronic pain concluded that it is effective on the basis of published findings and should now be updated with the inclusion of unpublished information made available through litigation.

I believe that the article by Vedula et al is particularly important because it shows what appears to be systematic manipulation of the analysis and reporting of multiple clinical trials of the same drug (but for different indications) that had the effect of making the drug appear efficacious when it likely was not. Furthermore, the manipulation was concealed. The published research articles did not completely describe what the intended primary efficacy outcome variables were, did not provide results in terms of these variables, and instead provided results only in terms of variables that were chosen post-hoc as new primary outcome variables.

To address that latter point, I independently reviewed three of the research publications cited by Vedula et al.(2,3,4) All three were noted to have reported significant results favoring gabapentin in terms of a primary efficacy outcome variable that was not identified as such in the corresponding studies' original research protocols or reports (see the supplementary data provided with the New England Journal article.) Per my review, none of the three published articles offered any hint that what they reported as primary outcome variables were not the variables originally chosen in that capacity, nor did they identify what those original primary outcome variables were, or how comparisons made using them turned out.

The implications of the article by Vedula et al are very important. Hence, I was surprised that the article appeared without an accompanying editorial to discuss these implications, and that its publication did not generate much media interest.

So that gives me an opportunity to comment further.

One could start with the implications for evidence-based medicine. As noted above, a short description of the evidence-based medicine is medicine whose practice is informed by critical, rigorous review of the best available evidence from clinical research as revealed by systematic search of the published research literature, as well as by the clinician's understanding of biology and the medical and biopsychosocial context, and by the patient's own values. Evidence-based medicine depends on critical, rigorous review, but the review process is generally done under the assumptions that research publications honestly describe what was done and what its results were. The review process was never designed to detect dishonest reporting or find information that was deliberately concealed. Manipulation of research (design, analysis, and implementation), concealment of that manipulation, and outright suppression of research threaten the foundations of evidence-based medicine. Yet the article by Vedula et al is part of a growing body of evidence that such manipulation, concealment and suppression are widespread, and done to serve vested interests, often commercial.

That is a huge problem for proponents of evidence-based medicine, but also for physicians who want their practices to be based on science, for patients who want their care to be based on science, and for all those in society who see the advancement of medical science as a way to improve peoples' lives.

As senior author Professor Kay Dickersin noted in an interview with Bloomberg "The trouble is, as a scientist, the publication has always been held up to me as the truth. It's the scientific record. What this study indicated is we can't believe that record."

Furthermore, to be a bit more concrete, most physicians, patients, and policy makers depend on what appears to be honest clinical research to make decisions about individual care and health policy. Deliberate and deceitful manipulation of clinical research to favor sponsors' products has likely lead to excessive use of and payments for drugs and devices that are less effective than advertised, if not useless or dangerous. Thus, it is likely that such manipulation is partially responsible for ever increasing health costs and poor health outcomes.

Finally, we need to start thinking about how we can detect and compensate for manipulation of clinical research in the past, and deter such manipulation in the future. One possible deterrent would be, as was noted by Vedula et al, detailed clinical trials registries that contain complete information about trial protocols.  For this to be effective, there need to be mechanisms to assure compliance, and penalties for non-compliance.  Moreover, since clinical research is now global, the registries must have global scope, and enforced assurance of compliance must also be global.

Registries might decrease future manipulation and suppression of research.   No one has suggested, as far as I know, a systematic way to detect and correct for previous manipulation. It would require a major, global investigative effort to uncover manipulation, and it would be a major scientific and policy endeavor to reveal most suppressed research and correct most manipulations.

However, before anything is done, patients, physicians and policy makers must acknowledge and understand the problem.  Yet it seems that even discussing these may be topics that are very uncomfortable for some of us. The longer we shrink from addressing them, however, the worse will be the results for patients, physicians, science and society.

References


1. Vedula SS, Bero L, Scherer RW, Dickersin K. Outcome reporting in industry-sponsored tirals of gabapentin for off-label use. N Engl J Med 2009; 361: 1963-1971. Link here.


2. Mathew NT, Rapoport A, Saper J et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001; 41: 119-128. Link here.


3. Vieta E, Goikolea JM, Martinea-Aran A et al. A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder. J Clin Psychiatr 2006; 67: 473-477.  Link here.


4. Caraceni A, Zecca E, Bonezzi C et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group. J Clin Oncol 2004; 22: 2909-2917. Link here.

Post Title → The Editorial that Wasn't: Evidence for Systematic Research Manipulation Undetectable by Critical Review

No Such RUC - The New England Journal Takes on the Primary Care Crisis, Sort Of

The vast amounts spent globally on health care do not seem to translate into access for many patients, quality care, and improved outcomes. The US, in particular, spends huge amounts, now more than $2 trillion a year, without getting universal access, or superb quality and outcomes. While we spend all this money, the primary care and generalist practitioners on the front lines of care are paid less and less, are increasingly embattled and disgruntled, and their numbers are rapidly thinning.

Although these problems are huge, there is not much clear discussion of them.

Thus, it was encouraging to see the vaunted New England Journal of Medicine, the premier US journal of medicine, take up the issue of the "future of primary care." A few weeks ago, the journal published a series of commentaries on the issue,(1-6) and the transcript of a round table discussion among their authors.(7) It was touted as the views of experts on "the crisis in U.S. primary care."

Unfortunately, although the series acknowledged some surface characteristics of the US health care system that have lead to this crisis, it did not delve further into its causes.

On the surface, a major cause of the crisis is that payments to primary care physicians are so limited that we are driving them out of business, while we pay lavishly for new, high-technology, often risky and invasive procedures.

However, understanding how and why this happens requires dissecting layer after layer of complex details. Doing so can be frustrating, if not eye glazing, and this may be one reason why the discussion of this pivotal issue has been so limited.

The first layer of complexity was implicitly acknowledged, but not discussed in the NEJM series. Bear with me through it.

The First Layer of Causation: Low Payments for Face-to-Face Visits, Rising Overhead

Physicians are paid for each encounter with a patient. Their pay only covers what they do in the presence of the patient, and not other efforts on patients' behalf, e.g., communicating with patients when they are not in the office, communicating with other professionals, paperwork required by insurance companies, etc, etc. Furthermore, pay for office visits is available only in a very small number of categories, and the pay for more complex visits is not commensurate with the increase in time and effort that they require, so that physicians who spend a lot of time trying to deal with complex problems will not be paid commensurate with their work. Pay for office visits has not increased as fast as inflation, and certainly not as fast as the expenses of running physicians' offices, i.e., office overhead, has increased. Thus, to try to maintain income, and to support increasingly complex office operations and overhead, primary care physicians must limit the time they spend with any one patient.

The result is the 15 minute visit for nearly all patients. But it is ridiculous to try to manage complex problems in 15 minute visits. Furthermore, primary care physicians spend hours of unpaid time doing paperwork, communications, etc.

The NEJM special articles dealt briefly with the contrast between how primary care physicians and proceduralists are paid, and the adverse effects of the 15-minute visit. The series coordinator, Dr Thomas Lee, noted that "procedure-oriented specialties offer higher potential incomes."(1) Dr Allan H Goroll decried the "current volume-driven, fee-for-service approaches," the "piecework payment system that perpetuates our 'hamster-wheel' environment."(4) Dr Thomas Bodenheimer asserted that primary care physicians are"overstressed by large patient panels." He blamed this on "the over-burdened 15-minute clinician visit."(3) He mentioned the 15-minute visit three other times in his commentary. In the round table discussion that accompanied the articles, he protested, "it's the tyranny of the 15-minute visit. If you come in to your practice in the morning and you see that you have 12 to 15 15-minute visits in the morning and another 12 to 15 15-minute visits in the afternoon, and you know you can't do it all in 15 minutes...."(7) Finally, in the round table discussion that accompanied the series, Dr Katherine Treadway offered the longest and most impassioned discussion, first explaining the problem,

Since I’ve been in practice a long time and I have an elderly, sick population, that for every hour of face-to-face time, I have another hour, at least, of time that I spend that’s unreimbursed. So, if I’m there for 13 hours, I’m getting paid for about 6 of the hours I’m spending.

and

The RVU system is ...designed for specialty care and single problems. There is nothing in the RVU system that allows you to take into account the fact that you’ve just seen somebody with congestive heart failure, hypertension, hyperlipidemia, coronary disease, renal insufficiency, and diabetes.

Why Are Payments Low for Face-to-Face Visits?

However, none of the commentaries addressed how we got to this pass, or, to continue the analogy above, none dissected the next layer. At best, they seemed to imply that this came about due to the forces of nature or an act of God. For example, in the round table discussion, Dr Lee said,

And I want to go to the payment system next. But do you think — I mean, which comes first, the chicken or the egg? Is it in the water and in the culture, in the educational values? And then the payment system may just reinforce that? Or is it the other way around, the payment system’s where it begins and that’s why it’s in the water?

To which Prof Barabara Starfield could only reply,

Unfortunately, it’s the chicken and the egg cycle. It doesn’t start in any one place.

The Role of the RUC

Actually, one can find the next layer of explanations in one place. The current bizarrely distorted manner in which physicians are paid was the act of people, a few people operating largely in the shadows.

The US Medicare system determines what it pays physicians using the Resource Based Relative Value System (RBRVS). This system determines the pay for every kind of medical encounter according to a complex formula that is supposed to account for physicians' time and effort, physicians' practice expense, and the cost of malpractice insurance. The components of physicians' effort assessed are, in turn, technical skill and physical effort; the required mental effort and judgment; and stress due to the potential risk to the patient.

To keep the system, which was started in 1990, current, requires addition of new kinds of encounters, which means encounters involving new kinds of procedures, and updating of the estimates of various components, including physicians' time and effort. To do so, the Center for Medicare and Medicaid Services (CMS) relies almost exclusively on the advice of the RBRVS Update Committee (RUC). The RUC is a private committee of the AMA, touted as an "expert panel" that takes advantage of the organization's First Amendment rights to petition the government. Membership on the RUC is allotted to represent specialty societies, so that the vast majority of the members represent specialties that do procedures and focus on expensive, high-technology tests and treatments. However, the identities of RUC members are secret, as are the proceedings of the group.

This opaque and unaccountable process has resulted in increases outstripping inflation in fees paid for procedures, while fees paid for "cognitive"medicine, i.e., for primary care, and for services that involve diagnosis, management of acute and chronic disease, counseling, coordination of care, etc, but not procedures, have lagged inflation. The effects of the RUC have been amplified by the unexplained tendency of commercial managed care and health insurance to track the RBRVS system when making their own payments to physicians.

For further details about the RUC, see these posts on Health Care Renewal (here, here, here, and here) and important articles by Bodenheimer et al,(8) and Goodson.(9)

The Unanswered Questions

Understanding this layer of the process raises some major questions, whose answers could help dissect the next layers.

• How did the government come to fix the payments physicians receive? Government price-fixing has not been popular in the US, yet this has caused no outcry.
• Why is the process by which they are fixed allowed to be so opaque and unaccountable? Why are there no public hearings on the updates, and why is there no input from practicing physicians or organizations other than the RUC?
• How did the RUC become de facto in charge of this process?
• Why does the AMA keep the membership on the RUC secret, and give no input into the RUC process to its general membership?
• Why is the RUC membership so dominated by procedural specialists? Why were primary care physicians, who made up at least a sizable minority of physicians when the update process was started, not represented according to their numbers?
• Why has there been so little discussion of the RUC and its responsibility for an extremely expensive health care system dominated by high-technology, expensive, risky and invasive procedures?

Of course, since the NEJM series failed to address the role of the RUC in the collapse of primary care, it could not raise, much less begin to answer such questions. The series mentioned the RUC only once, and virtually parenthetically, (by Dr Gorroll, who noted, "the current system "relies on the Relative Value Scale Update Committee [RUC] of the American Medical Association to set values for primary care services, despite the committee's marked overweighting in favor of procedural specialties...."[4]) Despite having written a key article explaining the role of the RUC,(8) Dr Bodenheimer was apparently only asked to write about practice innovations that could somehow compensate for continuing limits on the length of primary care visits.(3) It appears that it remains politically incorrect to question the RUC.

However, failing to understand, or even address the causes of the collapse of primary care will make it all the more difficult to find a way to revive it.

"Those who cannot remember the past are condemned to repeat it." attributed to George Santayana

References

1. Lee TH. The future of primary care: the need for reinvention. N Engl J Med 2008; 359: 2085-2086. Link here.
2. Treadway K. The future of primary care: sustaining relationships. N Engl J Med 2008; 359: 2086, 2088. Link here.
3. Bodenheimer T. The future of primary care: transforming practice. N Engl J Med 2008; 359: 2086, 2089. Link here.
4. Goroll AH. The future of primary care: reforming physician payment. N Engl J Med 2008; 359: 2087, 2090. Link here.
5. Starfield B. The future of primary care: refocusing the system. N Engl J Med 2008; 359: 2087, 2091. Link here.
6. Roland M. The future of primary care: lessons from the U.K. N Engl J Med 2008; 359: 2087, 2092. Link here.
7. Lee TH, Treadway K, Bodenheimer T, Starfield B, Goroll A. The future of primary care: perspective roundtable: redesigning primary care. Link here.
8. Bodenheimer T, Berenson RA, Rudolf P. The primary care-specialty income gap: why it matters. Ann Intern Med 2007; 146: 301-306. Link here.
9. Goodson JD. Unintended consequences of Resource-Based Relative Value Scale reimbursement. JAMA 2007; 298(19):2308-2310. Link here.

Post Title → No Such RUC - The New England Journal Takes on the Primary Care Crisis, Sort Of

BLOGSCAN - The Anechoic Effect and the HPV Vaccine

MedPundit notes that the New England Journal of Medicine's editorial on the HPV vaccine, which accompanied multiple original articles and commentaries on this topic, omitted any mention of how the manufacturer of the vaccine lobbied state legislatures to make administration of the vaccine mandatory. The anechoic effect lives (in medical journals, but not in blogs).

Post Title → BLOGSCAN - The Anechoic Effect and the HPV Vaccine

Two Cases Demonstrating the Reluctance of Medical Journals and Scientific Meetings to Air Criticisms of Vested Interests

Two follow-ups on stories recently discussed on Health Care Renewal demonstrate how hard it is to openly criticize the powers that be in health care in the venues on which most physicians depend for clinical and scientific information.

The American Society of Hypertension Panel on Conflicts of Interest

Last week we had posted about how the American Society of Hypertension had cancelled a scheduled panel discussion at its annual meeting about conflicts of interest and industry influence, after Society leadership decided the panel was too unbalanced. However, although the panel was likely to be critical of industry influence, it would have occurred at a meeting with considerable industry participation.

Now Christopher Rowland reports in the Boston Globe:

The American Society of Hypertension , accused by its critics of stifling debate, has reversed course and says it will host a panel discussion this spring on how pharmaceutical companies influence medical journals and societies.

After the cancellation was reported by the Globe last week, the society's associate executive director, Melissa Levine , said in an e-mail that the society had now decided to add the panel discussion to the agenda for the May meeting in Chicago.

The society is 'committed to conducting a session on conflicts of interest,' Levine said. 'Over the next few weeks we will be working to finalize the session and confirm the speakers.'

But the inclusion of drug industry defenders led one of the original invited panelists, Dr. Marcia Angell , former editor of the New England Journal of Medicine, to question the society's motives, even though she is considering taking part in the session.

'It seems to be standing the whole thing on its head,' said Angell.

She said the original intent of the panel had been to provide a counterweight to the drug industry's sponsorship of scientific papers and physicians at the annual meeting.

The industry advocates added to the panel are Dr. Thomas P. Stossel and William F. Keane.

Stossel, a Harvard Medical School professor and codirector of the hematology division at Brigham and Women's Hospital, said he has tentatively accepted an invitation to participate. He said he looks forward to the chance to defend drug industry involvement in medical societies.

Keane is vice president of clinical development at Merck & Co. Inc. Merck confirmed yesterday that Keane has been invited to present a lecture on 'industry/professional society relationships' but did not say whether he will accept the invitation.

Stossel said yesterday he would use the panel discussion to argue in favor of continued drug company participation and direct financial support of medical societies and doctors.

'There has been 20 years of unopposed air time of this anti-industry, anticommercial criticism,' Stossel said.

As we noted earlier, there is likely to be considerable commercial presence at the ASH meeting. At least 70 commercial exhibitors are expected in the exhibit hall. The Society is offering a variety of opportunities for corporate sponsorship of various meeting activities. Doubtless, many of the research projects to be presented were funded by industry, and many of the presenters are employed part-time by industry as consultants and on speakers' bureaus. Yet the Society seemed worried that a single panel presentation might exclusively present critics of industry, so it had to add an industry representative and an academic who has been an uncritical defender of industry to it. There may be some criticism of some practices by the pharmaceutical, biotechnology, and device industries in the media, but this case demonstrates how hard it is to criticize industry in more professional health care circles.

The "Defanged" New England Journal of Medicine Article on Epoetin

Last week, we posted about how the New England Journal of Medicine spiked a commentary by Dr Robert Steinbrook, one of its "national correspondents," that included discussion of commercial involvement in the National Kidney Foundation guidelines that promoted aggressive use of epoetin in anemic patients with renal failure. Instead, the Journal published a commentary by an author who has ties to the National Kidney Foundation, and which did not discuss or criticize the Foundation's commercial support. Steinbrook's commentary was eventually published in Lancet. [Steinbrook R. Haemoglobin concentrations in chronic kidney disease. Lancet 2006; 368: 2191-2193.]

This week the New England Journal of Medicine published another commentary by Dr Steinbrook entitled "Medicare and Erythropoietin." [Steinbrook R. Medicare and erythropoietin. N Engl J Med 2007; 356: 4-5. ] This version omitted any discussion, much less criticism, of industry involvement in these guidelines. Conspicuously absent was this passage found in Steinbrook's Lancet commentary:

Over the past decade, National Kidney Foundation guidelines have improved the clinical care of patients with chronic kidney disease in many areas, including vascular access and the adequacy of dialysis. They have, however, been questioned for their reliance on expert opinion and because of the close relations between the Foundation, the Kidney Disease Outcomes Quality Initiative (KDOQI) that formulates its recommendations, and the drug industry. In fiscal year 2005, according to its annual report, the Foundation received $19·7 million—57% of its total support—from various 'corporate and organizational partners'. In calendar year 2005, it received $4·1 million from Amgen and $3·6 million from Ortho Biotech, a subsidiary of Johnson & Johnson, the current marketers of epoetin products in the USA. Amgen supported the development of the anaemia guidelines and is acknowledged as 'the founding and principal sponsor of KDOQI.' 11 Of the 18 members of the workgroup, two-thirds disclosed financial associations with Amgen or other epoetin manufacturers or marketers. In an October, 2006, fact sheet, the Foundation responded to 'some controversy [that] has arisen due to the fact that KDOQI guidelines have been supported by industry. The NKF continually reviews its policies and procedures to safeguard the work product of KDOQI and to ensure that no sponsorship funds contributed to the NKF ever influence the content of any of the KDOQI guidelines.'

Steinbrook recommended,

Physicians and dialysis facilities need updated guidance about the management of anaemia and what is best for patients. Given the billions of dollars at stake for the drug and dialysis industries, such guidance is likely to receive the broadest acceptance if developed without industry support, and by experts without relevant financial associations. This might be accomplished under the auspices of the National Institutes of Health Consensus Development Program or the Agency for Healthcare Research and Quality.

Such a recommendation also did not appear in the New England Journal of Medicine article.

So it also seems that the New England Journal of Medicine could not bear to publish any discussion or criticism of commercial involvement in this particular instance of guideline development.

[Hat tip: GoozNews. As Merrill Goozner said, the Steinbrook article may have been "unspiked," but it surely was "defanged" in the process.]

Summary

Many physicians learn about clinical medicine, clinical science, and health policy from prominent journals and by attending prestigious scientific meetings. Yet these journals and meeting often are supported by commercial firms and other organizations with vested interests. These well-reputed fora, often regarded as objective, seem singularly reluctant to allow discussion of the role of commercial funding and influence in their proceedings. So not only are physicians who depend on these traditional sources of information likely to be exposed to information that is influenced by those with vested interests, they are unlikely to be exposed to any criticism of the biases that may thus arise.

Of course, in this age of the internet, there are other ways they may yet be exposed to such criticism. The longer the traditional journals and meetings try to pretend such criticism does not exist, the less trust they will inspire.

Post Title → Two Cases Demonstrating the Reluctance of Medical Journals and Scientific Meetings to Air Criticisms of Vested Interests

"Medical Journal Spikes Article On Industry Ties"

From the Wall Street Journal, an article that will pretty much speak for itself, with a little re-ordering and editing by yours truly. First, there was the spiked commentary,

The New England Journal of Medicine last month published studies warning that aggressive efforts to treat anemia in kidney-disease patients with the drug erythropoietin, or EPO, as recommended by the National Kidney Foundation, appear to increase the risk of heart failure and the need for dialysis. [See related posts here and here.] But the medical journal spiked an opinion piece commissioned from one of its senior writers that was critical of the foundation's reliance on multimillion-dollar donations from the companies that make such drugs.
Meanwhile, the author of the spiked editorial, Dr. Robert Steinbrook, submitted it to one of the journal's chief rivals, the British medical journal Lancet, which ran a version on its Web site on Nov. 17, a day after the New England Journal published its reports on the matter. [Steinbrook R. Haemoglobin concentrations in chronic kidney disease. Lancet 2006; 368: 2191-3.]

Dr. Steinbrook's article said that the foundation's guidelines have been questioned because of the group's close relationship with the drug industry. The article also noted that in fiscal 2005, the foundation received more than half of its support from 'corporate and organizational partners,' and, in the calendar-year 2005, it received $4.1 million from Amgen Inc. and $3.6 million from Johnson and Johnson's Ortho Biotech, the current marketers of EPO in the U.S.

The kidney foundation, which issued its recommendations earlier this year, credits Amgen as the 'founding and principal sponsor' of the guidelines. Such sponsorship is unusual -- the American Diabetes Association, for instance, says it doesn't 'receive or allow for any corporate contributions for our clinical practice recommendations.'

Ellie Schlam, a foundation spokeswoman, says Amgen's sponsorship money paid for guideline-development staffers, a $3,000 grant to each member for travel to meetings and other expenses, plus phone, faxing, copying and other administrative expenses. A disclosure on the foundation's Web site noted that most members of the guideline group have a financial relationship with either Amgen or dialysis providers, who resell EPO and stand to profit from its increased use. Still, the foundation says sponsors aren't informed or involved in any aspect of guideline development.

A spokesman for Amgen said the company is 'not involved in the creation and design of the guidelines we sponsor.'

The New England Journal declined to discuss Dr. Steinbrook's article, saying 'we discuss only content that we have published.' Dr. Steinbrook, a former deputy editor of the New England Journal, has been a national correspondent since 2002. According to a person familiar with the matter, he was told his manuscript lacked balance because it suggested that the commercial support of the guidelines influenced the medical recommendations made by that group. New England Journal editors also criticized the piece for failing to credit the guideline writers for striving to find the right balance when it comes to anemia guidelines.
Meanwhile, Richard Horton, editor of the Lancet, said 'I was surprised Robert came to us because I have admired his work for the New England Journal of Medicine.' Dr. Horton said of the article: 'We thought it extremely important -- because of the significant clinical implications and because of the questions it raised about the propriety of the arrangements over funding and guideline development.'

Then there was the more innocuous in-house editorial,

The journal did run a less-critical editorial on the studies co-authored by Julie Ingelfinger, a nephrologist and deputy editor at the journal who is the immediate past president of the Massachusetts-based chapter of the National Kidney Foundation and a member of the state group's medical advisory board. The editorial that ran made no mention of the foundation's industry funding, and Dr. Ingelfinger's relationship with the foundation wasn't disclosed.
Asked why Dr. Ingelfinger's roles at the Massachusetts Kidney Foundation weren't listed along with the article she co-authored, a spokeswoman for the New England Journal said, 'We publish financial associations that are relevant to the content of the article. We tend to be inclusive, rather than exclusive.'

Frank Davidoff, the editor emeritus of the Annals of Internal Medicine, says Dr. Ingelfinger's association with the kidney foundation should have been made known to readers. 'She should have disclosed that, even if she is the best person to write the editorial,' he said. Dr. Davidoff said medical journals historically have paid less attention to the potential conflicts of editorial writers than they have to researchers publishing original studies.

And the somewhat under-stated conclusion,

The handling of the two articles has reignited debate about the journal's standards and whether it is tough enough on issues involving industry funding of research and treatment guidelines.

Again, as we have stated before, people with conflicts of interest may not be consciously aware of the binds in which they find themselves. However, common sense, economics, and cognitive psychhology suggest people respond to incentives, including financial incentives (see post here). If a person or organization is paid by company x, how likely is he, she, or it to criticize company x's products? How likely is he, she, or it to give company x the benefit of the doubt?

Thus, at a minimum, we urge that all potential conflicts of interest affecting health care decision makers, and those who seek to influence them, ought to be fully and thoroughly disclosed. And we need to consider whether some such conflicts ought to be banned outright.

But people with conflicts, who are now prevalent in academic medicine, and various other health care organizations, are likely to find such discussions very uncomfortable. But that is just why we need to have them.

Post Title → "Medical Journal Spikes Article On Industry Ties"

A Former Editor Cites Foucault

A while back, we posted about the firing of the editors of the Canadian Medical Association Journal (CMAJ), noting this seemingly unfortunate example of a power struggle within a medical organization. However, the firing of Dr Hoey has generally been presented in terms of abuse of power as a violation of editorial independence.

For example, in 2005, Hoey wrote an unsigned editorial in CMAJ that started with the premise, "freedom from interference in editorial decisions stands at the heart of the credibility of any reputable journal." He then announced "we have a transgression to report," and then went on to recount how "a CMA [Canadian Medical Association] executive objected strenuously to a news article we were preparing on behind-the-counter access to levonorgestrel (Plan B)."(1) Similarly, the editor of the British Medical Journal responded to Hoey's firing, "this is a sorry tale that shows how little the CMA (its officers and - since there is no sign of a concerted outcry from them - its members) understands what it means to be the custodian of an international academic medical journal."(2)

There has been much more discussion of the firing of Hoey and then the departure of many other CMAJ editors. The New England Journal of Medicine ran a commentary in March.(3) Last week, it ran another, this time written by Dr Hoey, himself.(4) Would this more clearly delineate what happened?

Hoey's article, however, took an unusual stance. He chided "owners [who] may wish to limit to limit the scope of their journal, to restrict its editorial perspective to matters of bedside medicine and the narrower interests (as perceived by the usually nonphysician publishers) of their physician readership." He then denied this "vision." Instead, he proclaimed, "for Foucault, medicine is a political act."

That is where he lost me, decisively. The Foucault he cited, assuredly is Michel Foucault, one of the "postmodern vanguard," authorities repeatedly cited to justify the fashionable post-modern concepts that have swept through the academic humanities and social sciences. Foucault is cited:

• For his hostility to the Enlightenment. For example, he wrote, "it is meaningless to speak in the name of -or against - Reason, Truth, or Knowledge."(5) Hicks explained, "Postmodernism rejects the entire Enlightenment project. It holds that the modernist premises of the Enlightenment were untenable from the beginning and that their cultural manifestations have now reached their nadir. While the modern world continues to speak of reason, freedom, and progress, its pathologies tell another story. The postmodern critique of these pathologies is offered as the death knell of modernism: 'The deepest strata of Western culture' have been exposed, Foucault argues, and are 'once more stirring under our feet.'"(6)
• To support the self-contradictory and ultimately meaningless assertion that there is no external reality, that reality is "socially constructed." "Foucault at times suggested that underlying what counts as objective knowledge is a power relation, one category of people benefiting at the expense of another category of people. The radicals thus see the social construction of reality...."(7)
• To support totalitarianism. "As part of the attack on the Enlightenment, the critique of truth suffers from a tendency to reinforce pre-enlightenment despotism. The Enlightenment replaced individual and institutional power with more objective measures of validity, and it is no surprise that the rejection of objectivity collapses back into power as a means for defining absolute truth."(8) Foucault's belief that "liberal democracies are actually more oppressive than medieval despots or even modern totalitarians,"(9) was consistent with his occasional embrace of totalitarian rulers. In 1971, he said, "when the proletariat takes power, it may be quite possible that the proletariat will exert toward the classes over which it has triumphed a violent, dictatorial, and even bloody power. I can't see what objection could possibly be made to this."(10) Similarly, he extolled the 1978 Iranian revolution, "exulting in the 'intoxication' of revolution and the violent expression of 'collective will,' and praised its leaders 'political spirituality,' which he thought reflected a health 'religion of combat and sacrifice.'"(11)

In my humble opinion, citing Foucault as an authority suggests a sympathy for post-modernism that would not be helpful to a journal editor. Most of editing is about science, and science does not fit with the notion that external reality does not exist. Readers of Health Care Renewal are certainly aware that medicine and health care are influenced by politics. But the notion that politics is all of medicine, or a totalitarian world view will not help us address concentration and abuse of power.
But perhaps Hoey's citation of Foucault was a mistake, or misinterpretation. After citing Foucault, Hoey admonished journal editors not to discuss or even divulge editorial decisions to their publishers, for that would "gut the editorial independence of a journal." However, the editor's outlook and assurance should include "an eager propensity to poke a stick into something or somebody." That proclamation suggests that Hoey's reliance on Foucault was not some mistake. Characterizing an ideal journal editor as an undisciplined trouble-maker fits Foucault's fascination with "limit experiences."(12) Yet editors whose main joy is in poking sticks into something or somebody without restraint or accountability will only add to concentration and abuse of power.
Thus, it still seems like our original characterization of the dispute at CMAJ was apt, "A classic power struggle within medicine's increasingly less-hallowed halls. Here it seems drearily familiar." That's too bad.
References
1. CMAJ. The editorial autonomy of CMAJ. Can Med Assoc J 2006; 174: 9.
2. Godlee F. A big mistake. Brit Med J 2006; 332:
3. Shuchman M, Redelmeier DA. Politics and independence - the collapse of the Canadian Medical Association Journal. N Engl J Med 2006; 354:1337-1339.
4. Hoey J. Editorial independence and the Canadian Medical Association Journal. N Engl J Med 2006; 354: 1982-3.
5. Hicks SR. Explaining Postmodernism: Skepticism and Socialism from Rousseau to Foucault. Tempe: Scholargy Publishing, 2004. P. 2. (Link here)
6. Hicks, P. 14.
7. Farber DA, Sherry S. Beyond All Reason: the Radical Assault on Truth in American Law. New York: Oxford University Press, 1977. P. 24. (Link here)
8. Farber, Sherry. P. 106.
9. Farber, Sherry, P. 29
10. Lilla M. The Reckless Mind: Intellectuals in Politics. New York: New York Review of Books, 2001. P. 150. (Link here.)
11. Lilla. P. 154.
12. Lilla. P. 150.

Post Title → A Former Editor Cites Foucault

The New England Journal of Medicine Weighs in on the TGN 1412 Trial Debacle, But With a Twist

The New England Journal of Medicine published a commentary on May 4, 2006, on the ill-fated trial of TGN 1412. (Wood AJJ, Derbyshire J. Injury to research volunteers - the clinical-research nightmare. N Engl J Med 2006; 354: 1869-1871.) The first author of the study, Dr Alastair JJ Wood, will be joining Symphony Capital as a managing director in August, according to a New York Times article published May 2, 2006. Per the Times, "Dr Wood has been working as a consultant to Symphony since the fund's inception in 2002.... Symphony, which has $315 million under management, invests in particular drugs. It buys the rights to a drug from a biotechnology company and then works with the company to conduct clinical trials. The biotech company has the right to buy back the drug later at a specified price."

We have previously posted, most recently here, about the disastrous trial, implemented by Parexel International , of a new monoclonal antibody designated TGN 1412, manufactured by TeGenero AG. All six healthy volunteers who got the antibody soon became critically ill.

Unlike some other cases discussed on Health Care Renewal, this one had already received attention in prominent UK medical and scientific journals, including the British Medical Journal, the Lancet, and Nature. It's good to see that the most prominent US medical journal has weighed in.

The article by Wood and Derbyshire focused on the following points, in the article's own words (with emphasis added):

At some point in the development of every drug, the drug must be given for the first time to humans in a phase 1 trial. Until now, such trials have had a remarkably good safety record....
It is standard practice to begin with very small doses, often orders of magnitude below those determined to be nontoxic in animals and those expected to produce any effect in humans. Doses are then increased slowly, as the experience at lower doses is continually evaluated.
System or human failures — such as errors in dosage, manufacturing, or administration — are usually prevented by rigorous procedures for drug preparation and administration.
Toxic effects such as acute liver injury, leukopenia, cardiac arrhythmia, or rash may be related to the new drug molecule itself but unrelated to its intended mechanism of action. Considerable efforts are made to identify these types of toxicity in vitro and through studies in animals. However, our incomplete understanding of the mechanisms underlying such toxicity and the limitations of animal models inevitably mean that some potentially serious toxic effects go undetected in preclinical screening....
The second type of toxic effect results from the action of the drug on its intended biologic target. Such effects are always unknown when a target is 'drugged' for the first time — and there must always be a first time.
When a compound addressing a new biologic target is tested for the first time in humans, much greater caution must be exercised. Such caution should include avoidance of treating multiple volunteers simultaneously or without a reasonably long interval between them.
In some cases, a phase 1 trial does not, in fact, represent the first attempt to manipulate a particular biologic target — though the researchers may be unaware of previous efforts. Clearly, we should not be exposing people to such manipulation if it has been shown, in studies in either humans or animals, to carry serious risks outweighing any potential benefits.
Unfortunately, the companies that generate early safety data consider them proprietary — a concern that must somehow be reconciled with patients' safety. Volunteers rightly expect that we put their safety before competitive advantage, and researchers have an ethical obligation to prevent the exposure of additional volunteers to previously identified risks.
How can we improve the knowledge base for designing trials of new drugs directed at novel targets and make it available to developers and regulators when they are considering the safety of such trials? One approach would be to ensure that all data from preclinical drug research are held in a secure database, indexed by biologic target, and accessible only by major regulatory authorities, which are used to handling confidential data.
There are fundamental questions about which, if any, details of a clinical trial involving volunteers should ever be confidential or whether safety and ethics principles can be ensured only by an open, transparent process in which such trials and protocols are registered in a public database.

The commentary presented a reasonble summary, but it seemed to tread lightly in certain areas.

In particular, it side-stepped the question of whether that there was particular information available before the TGN 1412 trial that would have suggested that affecting the CD28 receptor targeted by TGN 1412 might be dangerous. There is at least a question about this. An article in the (UK) Times quoted Angus Dalgleish, "the previous studies which caused similar side effects were in patients already suffering from cancer, but [the researchers] should have known they would get a meltdown because the drug was hitting exactly the same target." An article in Nature (Hopkin M. Can super-antibody drugs be tamed?) stated, "with hindsight, it might be no surprise that the compound, dubbed a 'superagonist' antibody by its creators, could run amok in the immune system." Furthermore, research on drugs that target the CD3 receptors in mice, which have a similar function to the CD28 receptors, showed, "uncontrolled cytokine release was a problem - albeit not a large one because the mice were already immunodepleted...."

Furthermore, the New England Journal commentary did not address questions about whether the research subjects in this trial really gave informed consent. This question was raised in, among other places, a commentary in the British Medical Journal (Goodyear M. Learning from the TGN 1412 trial: this experience should foster an open culture in medical research. Brit Med J 2006; 332: 677-678.) See also our posts here and here.

Finally, it did not challenge the notion that safety data about particular drugs should be kept confidential during drug development. In constrast, Goodyear (see above), wrote, "this tragedy creates one more imperative for an open culture in medical research, a culture that many fear is increasingly losing its way."

Given that Dr Wood, the first author of this article, already consults for and will soon become a top leader in an organization that buys rights for particular drugs from biotechnology companies and then helps to run clinical trials on them, his choice of emphasis is understandable. Perhaps someone from a different background would have placed emphasis elsewhere.

But it is time for the final twist. The New England Journal only identified Dr Wood as "a professor of medicine and pharmacology at Vanderbilt University School of Medicine." It did not mention Dr Wood's current or future positions with Symphony Capital. Yet Dr Wood's new position at Symphony Capital had been made public by the New York Times two days before the article was published.

It seems that prominent medical journals still have difficulties disclosing financial and other interests of authors that might meaningfully affect their opinions, and might be relevant to readers who want to understand where these authors are coming from.

Post Title → The New England Journal of Medicine Weighs in on the TGN 1412 Trial Debacle, But With a Twist

Caught in the Cross Fire: The Wall Street Journal vs the New England Journal of Medicine

This week, the Wall Street Journal ran an editorial attacking the New England Journal of Medicine. [Anonymous. New England journal of politics. Wall Street Journal, January 16, 2006. Not yet available online.]

The editorialist was bothered that the New England Journal of Medicine published an unusual editorial "Expression of Concern." (Curfman GD, Morrisey S, Drazen JM. Expression of concern: Bombardier et al., "comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis," N Engl J Med 2000; 343: 1520-8. N Engl J Med 2005; 353: 26.) about a study it had previously published of rofecoxib (Vioxx). (See our post here.)

Here is what the Wall Street Journal said:

The New England Journal is joining the ranks of academic publications risking their reputations as non-partisan arbiters of good science in order to rumble in the political tarpits.
The facts and timing of the Merck ambush certainly suggest as much. Late last year the New England Journal published an 'Expression of Concern' about a Vioxx study it carried in 2000, baldly accusing researchers of omittin key data to make the painkiller appear more safe.
What has Dr. Curfman [Executive Editor of the New England Journal] in a dither is the fact that three more participants [in the group treated with Vioxx] also suffered heart attacks - although only after the cutoff date that had been determined by an outside safety panel for the study.
In fact, as prominent scientists have since attested, the authors were simply following the rules of science. 'If the outcomes truly occurred after the close of the study, then they don't belong in the study,' Brian Strom, an epidemiologist at the University of Pennsylvania, told Nature magazine. [See link here.]
The New England Journal clearly knew all this, and as an esteemed professional body presumably understood the scientific rationale behind the omission. Yet it nonetheless chose to use the Vioxx trial as an opportunity to join in the latest political and legal tarring of Big Pharma as greedy profiteers.
Unfortunately, the attack on Merck isn't isolated, but is part of a growing trend among scientific journals that have joined business-bashing and other liberal campaigns.

Here we go again.

Now that discussion of health care reform is in the air again, maybe it's not surprising that health care issues will be caught in the country's usual right-left cross-fire.

However, framing the debate with political slogans often precludes hearing about a lot of good ideas.

By the way, although I can think of instances in which the New England Journal may have made editorial decisions consistent with thinking currently fashionable on the academic left (for example, see this post), it is not obvious that the Expression of Concern was published for political reasons, or to bash business.

There is also a reasonable argument that Merck should not have withheld data on the three patients who died after treatment with Vioxx. Although a cut-off date for the trial was pre-specified, it resulted in different durations of follow-up for different patients. There is an argument to include adverse events that occurred after the pre-specified trial cut-off date, but not as long after trial enrollment as the period of follow-up used for patients enrolled earlier in the course of the trial.

In my humble opinion, one reason that we have made so little progress in solving the classic problems with costs, access, and quality is that the solution often get caught in these sorts of debate.

If one goes back to the early 1990s, before the abortive attempt by the Clinton administration to reform health care, such debates were common. At that time, many of the chief proponents of managed care were from the Jackson Hole group, which was heavily backed by the pharmaceutical and commercial insurance industries.[1,2] On the other side, promoted national health insurance, were groups such as Physicians for a National Health Plan, some of whose leaders had advocated Marxism.[3]

After the failure of the Clinton plan, there was a surprising reprise of this debate in the pages of the American Journal of Public Health. On one side was was Howard Waitzman MD, who had written "A Marxist view of health care,",[4] and on the other side, Professor Alain C Enthoven, one of the foremost figures in the Jackson Hole group.

Waitzman started by noting Enthoven's past work for the Defense Department during the Vietnam War.[5] Enthoven fired back by decrying "Waitzkin's Marxist vision of a socialist America that would produce a socialist health care system...." [6] Waitzkin then responded by charging Enthoven with being responsible for the "rapid deployment of Minuteman and Polaris nuclear missiles during the 1960s and 1970s. Many have argued that such weapons increased, rather than decreased the risk of nuclear war." [7]
You Marxist. You war-monger. Just like that old comedy routine on TV.

I respectfully submit that slugging matches of this sort did not and will not advance the renewal of health care.

References

1. Priest D. Health care theorists of Jackson Hole: policy heroes or special interests? - "Managed competition" group says industry’s role is only natural. Washington Post, March 12, 1993. P. A15.
2. Toner R. Hillary Clinton’s potent brain trust on health reform. New York Times, February 28, 1993. P. 3.1.
3. Himmelstein DU, Woolhandler S. The corporate compromise: a Marxist view of health maintenance organizations and prospective payment. Ann Intern Med 1988; 109: 494-501.
4. Waitzkin H. A Marxist view of health care. Ann Intern Med 1978; 89: 264-278.
5. Waitzkin H. The strange career of managed competition: from military failure to medical success? Am J Pub Health 1994; 84: 482-489. [Abstract here.]
6. Enthoven AC. Commentary: setting the record straight - a reply to Howard Waitzkin. Am J Pub Health 1994; 84: 490-493.
7. Waitzkin H. A rejoinder from Waitzkin. Am J Pub Health 1994; 84: 493-494.

Post Title → Caught in the Cross Fire: The Wall Street Journal vs the New England Journal of Medicine

The New England Journal Charges Merck Suppressed Vioxx Research Results: "One Horrible Debacle in American Medical History"

Late last week, the New England Journal of Medicine published an unusual Editorial "Expression of Concern." (Curfman GD, Morrisey S, Drazen JM. Expression of concern: Bombardier et al., "comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis," N Engl J Med 2000; 343: 1520-8. N Engl J Med 2005; 353: 26.)

The editorial stated that an article in journal which reported on VIGOR trial, which compared Merck's drug rofecoxib (Vioxx) with naproxen, omitted mention of cardiac adverse events that were known to the study's authors before the final version of the manuscript was submitted to the journal. Specifically, the editorial states that at least two of the authors knew that three patients who had received rofecoxib in the trial had suffered myocardial infarctions (heart attacks), but did not include these patients in their calculations of adverse events. Furthermore, some of the authors were apparently aware of "other data on cardiovascular adverse events that we believe would have been relevant to the article," but did not include this data in the article.

Subsequent interviews with Dr. Curfman revealed that the two authors who knew about the extra adverse events were both Merck employees (Toronto Star, Dec. 8). The only two Merck employees now known to be authors were Dr. Alise Reicin, Vice President for Clinical Research, and biostatistician Dr. Deborah Shapiro. When Curfman was giving a deposition for a case brought against Merck, he was shown a Merck internal memo dated July 5, 2000, two weeks before the VIGOR authors submitted a revised but not final version of the manuscript to the journal. The memo suggested that three patients had suffered heart attacks, yet that data was not included in the revised (or final) version of the paper. Curfman also said,

We hope by issuing the statement of concern that it will be a stark reminder to the science community, to the scholarly community, that if we don't his this principle of trust, that the whole scholarly process is just going to collapse into rubble.

Merck's response was a statement, "These additional events were disclosed to the FDA in 2000, presented publicly at the FDA's advisory committee in February, 2001, and included in numerous press releases subsequently issued by Merck. We also note that these additional events did not materially change any of the conclusions of the article."

Forbes reported that "a pre-submission version of the study from which data, including the number of heart attacks and deaths, were deleted by a Merck editor two days before submission." Forbes also quoted Dr. Eric Topol,

This is one horrible debacle in American medical history. I've never seen the likes of this.

Curfman talked more to the Boston Globe (Dec. 10, 2005), admitting that he should have been more skeptical about the VIGOR trial article. In particular, the authors of the study suggested that any apparent differences between adverse cardiac events for patients receiving rofoecoxib versus naproxen were due to a protective effect of naproxen. Curfman said, "I should have been more diligent in questioning the hypothesis at the time."
The Globe also reported that some of the plaintiffs' attorneys involved in Vioxx litigation are questioning whether Merck Vice President Reicin may have commited perjury. Attorney Mark Lanier said that he plans "on using it [the New England Journal editorial] to show that she's been less than honest with other juries." Furthermore, "What a jury is going to get is A, Merck fudged on the details, B, the fudge was in their favor, C, it was on purpose, D, Merck lied about fudging, or at least covered it up. And E, the most prestigious medical journal in the United States of America has called their hand and said this is unethical and wrong."

The evidence that Merck was reluctant about disclosing research data unfavorable to Vioxx just gets stronger and more extensive. We can only hope that this increasingly sad case will force pharmaceutical companies, and other large health care organizations, to be more open, transparent, accountable, and honest.

It would help if health care professionals united to demand these changes. Bravo, at least to Dr. Curfman and the other editors of the New England Journal, and Dr. Eric Topol, for speaking up.

[Update as of Dec 19, 2005: Merck's full statement in response to the New England Journal of Medicine editorial statement, and its news coverage, is on the Merck web-site. To quote the statement in more detail than provided above,

The article in the NEJM was based on cardiovascular data reported as of a prespecified cutoff date established by the Company. The reason for specifying a cutoff date in advance were to ensure that the data analysis could be completed in a prompt manner and to avoid any later allegation that the data were manipulated.
All potential CV serious adverse experiences eligible for adjudication that had been reported to Merck by the cutoff date, February 10, 2000, were referred for adjudication and the confirmed events formed the basis of Merck's communication on the primary study data.... The NEJM thus received the data that was part of the primary analysis.
Any additional CV events eligible for adjudication but reported to Merck after the February 10 cutoff date were subsequently adjudicated.
Merck used other means to disclose the additional information.
The statement of concern by the NEJM editors may have left the mistaken impression that the updated data, including the 3 additional MIs on rofecoxib, were in the original draft version of the manuscript submitted to the NEJM but deleted before submission. That is incorrect. The basis for this misimpression was a document submitted electronically to the NEJM that simply showed the deletion of a header and footers for a table discussion cardiovascular events in the study. There was no data in the table.

As some other bloggers might say, "read the whole thing," and see what you think.]

Post Title → The New England Journal Charges Merck Suppressed Vioxx Research Results: "One Horrible Debacle in American Medical History"