a study worth looking into…

Posted on Wednesday 27 May 2015

This is a released-on-line version of a new meta-analysis of SSRIs in pediatric depression. Be warned that I’m not going to try to vet all their analytic techniques [as they do some pretty heady mathematical pyrotechnics to derive their various curves]. I’ll just say that in-so-far-as I understood it, it appeared legit to me. They looked at the results of thirteen pediatric trials and compared them to forty adult trials:
Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder
by Varigonda AL, Jakubovski E, Taylor MJ, Freemantle N, Coughlin C, Bloch MH
Journal of the American Academy of Child & Adolescent Psychiatry 2015, Published on-line in advance.

Objective: Selective serotonin reuptake inhibitors [SSRIs] are the first-line pharmacological treatment for pediatric major depressive disorder [MDD]. We conducted a meta-analysis to examine [1] the time-course of response to SSRIs in pediatric depression, [2] whether higher doses of SSRIs are associated with an improved response in pediatric depression, [3] differences in efficacy between SSRI agents; and [4] whether the time-course and magnitude of response to SSRIs is different in pediatric and adult patients with MDD.
Method: We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs to placebo for the treatment of pediatric MDD. We extracted weekly symptom data from trials in order to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on standardized mean differences between treatment and placebo group.
Results: Meta-analysis included 13 pediatric MDD trials with a total of 3,004 patients. A logarithmic model indicating the greatest benefits of SSRIs occurred early in treatment best fit the longitudinal data {log [week] =0.10 [95% CI, 0.06 to 0.15, p<0.0001]}. There were no significant differences based on maximum SSRI dose or between particular SSRI agents. SSRIs were demonstrated to have a smaller benefit in pediatric compared to adult MDD.
Conclusion: Treatment gains in pediatric MDD are greatest early in treatment and are on average minimal after 4 weeks of SSRI pharmacotherapy in pediatric MDD. Further research is needed using individual patient data to examine the power of early SSRI response [e.g. 2-4 weeks] to predict outcome in short-term pharmacological trials.

[reformatted to fit]
The SMD [Standardized Mean Difference] is the Effect Size [mean difference from baseline corrected by the pooled Standard Deviation – essentially Cohen’s d] using the study’s main depression scale [HAM-D, MADRS, CDRS-R, or K-SADS-P] from the Observed Cases.
"The larger the effect size, the greater the difference between treatment groups in the outcome measure. There are no universally accepted standards for describing values of d. However, it has been suggested that an effect size of 0.8 (8/10ths of a standard deviation) is “large,” a value of 0.5 (half a standard deviation) is “medium,” and a value of 0.2 (one fifth of a standard deviation) is small."
from the BMJ Endgames by Philip Sedgwick
The graph on the left [above] is the raw weighted compendium of all thirteen studies and shows that the the major change is in the first several weeks. The graph on the right compares the response of adults and children [this time they used curve fitting mathemagic]. The point is obvious – the pediatric response is dramatically less than adults by more than a half. By classic interpretation of Effect Sizes, this is in the small or weak range.

[recolored and reformatted to fit]
This second set of graphs is dramatic – with the therapeutic effect evaporating as we come forward in time. I think the effect demonstrated is real, but I want to chase their mathemagic a bit before commenting too much here, This is the elusive phenomenon has been variously attributed to increasing placebo effect, differing patient populations, the coming of the CROs – but no explanation has received universal support. And these investigators who seem skilled and competent were hampered by having to use indirect methods because they didn’t have full data access.

There are interesting findings scattered throughout this meta-analysis. The choice of drug or dose didn’t seem to matter [think about all the time clinicians expended listening to the comparative hype from the pharmaceutical reps and KOLs spread under our noses].

I wanted to give credit where credit is due. This may be the first time I’ve read the part in red below said so matter-of-factly particularly in the JAACAP. Also it was "reviewed under and accepted by deputy editor John T. Walkup, MD" rather than Editor Andre Martin [for those of you who follow the retract Paxil Study 329 efforts].
"Systematic reviews and meta-analyses regarding SSRI pharmacotherapy in pediatric depression have been common. These meta-analyses have demonstrated that SSRI pharmacotherapy is effective for pediatric depression. SSRIs as a class provide around a 25% greater chance of responding over the short-term when compared to placebo and have a number needed to treat [NNT]=10. Meta-analysis of response rates in pediatric antidepressant trials are high [61%], but so is the response rate to placebo [50%]. Systematic reviews have demonstrated that treatment estimates of SSRI efficacy were previously exaggerated by publication bias and time-lag bias in the distribution of negative trial results."
And the article mentions and lays out the AACAP’s practice guidelines for SSRIs in the article. That last line in red is absolutely correct. In light of the findings of the much lower efficacy of these drugs in adolescents it seems ludicrous to have the same guidelines for both adults and children given its near inertness in the latter:
"Regarding the use of SSRIs in pediatric depression, the American Academy of Child and Adolescent Psychiatry [AACAP] Practice Parameter recommends that “patients should be treated with adequate and tolerable doses for at least 4 weeks. Clinical response should be assessed at 4-week intervals, and if the child has tolerated the antidepressant, the dose may be increased if a complete response has not been obtained. At each step, adequate time should be allowed for clinical response, and frequent, early dose adjustments should be avoided. However, patients who are showing minimal or no response after 8 weeks of treatment are likely to need alternative treatments. Furthermore, by about 12 weeks of treatment, the goal should be remission of symptoms, and in youths who are not remitted by that time, alternative treatment options may be warranted.” These AACAP recommendations mimic American Psychiatric Association [APA] Practice Guidelines in adults with MDD."
Another finding of interest – that the bulk of the effect was in the first week  [or two]. That’s in stark contrast to the reports in adults or my experience using them. They want to propose shorter clinical trials or something like that. I wondered if it wasn’t evidence of the response to an active placebo. Whatever the case, I’m reporting this study because of its documentation of the low efficacy in adolescents compared to adults, and will get back to these other findings after some reflection. It feels like a study worth looking into more deeply…
Mickey @ 7:21 PM

unserious arguments seriously…

Posted on Wednesday 27 May 2015

This is my own sixth blog on the recent NEJM series in just over a week [a contrarian frame of mind… , wtf?…, wtf? for real…, a narrative…, and not so proud…]. The Drazen/Rosenbaum pieces may well be on the way to being the most-blogged journal articles since Paxil Study 329 – a rite of passage for new bloggers in the pharmascold set [while I don’t consider myself a pharmascold, Drazen/Rosenbaum might be turning the category into highest virtue]. I took the approach of looking into the history of the NEJM editor who would write/publish such a thing. Richard Lehman, a retired physician who writes a journal-watch for the BMJ, takes a more direct route:
[NEJM 21 May 2015 Vol 372]
British Medical Journal
26 May, 15

The NEJM has the highest reputation of any medical journal, so it’s impossible not to feel dismay when it lets its standards slip towards the near-nonsensical. When the first part of Lisa Rosenbaum’s three-part series on conflicts of interest appeared, I wondered if it might be some kind of elaborate joke: but sadly it seems not. I hate to see it when a clearly talented young writer is encouraged to write below standard, and at great length for no obvious reason. This final article, “Beyond Moral Outrage,” is an attempt to describe people who worry about conflicts of interest as beyond rationality. In a typical section she writes: “As Haidt concludes, moral reasoning is not ‘reasoning in search of truth,’ but rather ‘reasoning in support of our emotional reactions.’” Interesting that Haidt was actually citing an example not of moral reasoning but of emotional reasoning from the start [unless you count putting the American flag down the toilet as a moral issue], and in which no-one was harmed. Is Lisa actually suggesting that the pharmaceutical industry just flushes away used American flags and has never harmed anyone or concealed harm? But there I go — I am responding to wholly unserious arguments seriously, which I suppose must be the purpose of this exercise. I think the NEJM has shot itself in the foot. And also exposed some awful editorial decisions. Please, if you are going to publish someone attempting to persuade us against bias, don’t let through a sentence like “Being a pharmascold conferred the do-gooder sheen many of us coveted.” The only unbiased words in it are “being,” “a,” “the,” and “of”…
"But there I go — I am responding to wholly unserious arguments seriously" may well be the final message – this series may have a meaning, but it’s not in its frivolous content. And perhaps I should follow Lehman’s lead and look at the meta-side of what I’ve been writing. My posts are about the NEJM as I’ve known it over my life, and I can’t say enough positive things about the Editors that have come before – Arnold Relman, Marcia Angell, and Jerome Kassirer. Could I be indirectly lobbying for the NEJM to start searching for a new editor who honors the two centuries of integrity of my NEJM? When I put that question to myself directly, my mind responds, "Damned Straight!" I do notice that I’m using expletives along the way on this topic ["wtf?" x 2, and Damned Straight!"], something I do to add emphasis. So I not so secretly hope that the powers that be at the NEJM are thinking similar thoughts after reading the negative reactions to this editorial and series.The other very real possibility is that Drazen/Rosenbaum are speaking for those powers that be, and my NEJM is just the anachronistic fantasy of an old guy.

So long as I’m trying to be genuinely introspective, I fear that the second alternative is far more likely. In an article about the firing of Jerome Kassirer and the hiring  of Jeffrey Drazen [Editor Forced to Resign in Dispute Over Marketing of Medical Journal’s Name], it said of Marcia Angell,
"Dr. Marcia Angell succeeded Dr. Kassirer as editor in chief pending a search committee’s choice of a new editor. Dr. Angell, who was a finalist, withdrew recently as a candidate and said she was retiring to write a book on alternative medicine."
I don’t believe that in light of her later editorial comments [The Journal and Its Owner — Resolving the Crisis and Is Academic Medicine for Sale?], her pieces in the New York Review of Books [The Epidemic of Mental Illness: Why? and The Illusions of Psychiatry], and the book she did write [The Truth About the Drug Companies: How They Deceive Us and What to Do About It]. I think she wouldn’t  go in the direction she knew they were heading [or at least that’s what I wish]:
"It is no secret that the other Journal editors and I were dismayed by the society’s decision to let Kassirer go, and that we shared many of his concerns about the use of the Journal’ s name to promote other products. The society’s action precipitated a crisis unique in the Journal’s 187-year history. There was even talk of a mass resignation by the editors, an event from which the Journal might never have recovered. Faced with the possibility of irretrievably damaging the Journal, both the society and the editors drew back from the brink. After intense discussions between the society’s leadership and the editors, Evjy and I issued a joint statement on August 4…"
I find myself almost wishing they had "gone to the brink" and beyond all those fifteen years ago and called the question. It may  have gotten us on the road earlier. I don’t fault Relman, Kassirer, and Angell at all. They’re four-out-of-four-star heros of the realm in my book. But in hindsight, I’m afraid it’s hard for me to imagine that Dr. Drazen would’ve written "Revisiting the Commercial–Academic Interface" which challenges a firm NEJM policy without having the backing [or even urging] of the "owners" – the New England Medical Society. I wish I didn’t think that – but I do. Sigh…
Mickey @ 9:12 AM

beyond the borders…

Posted on Tuesday 26 May 2015

If you follow these things, you’ve already read this NYT Op-Ed. But I’m still going to post it in toto as a testimony to people like Carl [and Mike and Mary and Leigh] who will persevere against any kind of gradient they meet until the job gets done. They intuitively knew that what happened to Dan Markingson was a lot more than just another tragic casualty of someone with Schizophrenia [as if that’s not bad enough]. They saw that it was a was a pointer to a whole system that was corrupted in a very specific way, and they were absolutely correct. Here, Carl focuses in on the piece of the system charged with ferreting out such things and protecting research subjects from things like this happening – the Institutional Review Boards. That was certainly not the only problem at the University of Minnesota, to be sure. But it’s the designated "cop" in the system, and it just didn’t function, not just with Dan’s case, but in general. It’s supposed to be an anchor, but at the "U", it was just another weak link in an altogether weak chain.
New York Times
By CARL ELLIOTT
MAY 26, 2015

IF you want to see just how long an academic institution can tolerate a string of slow, festering research scandals, let me invite you to the University of Minnesota, where I teach medical ethics.

Over the past 25 years, our department of psychiatry has been party to the following disgraces: a felony conviction and a Food and Drug Administration research disqualification for a psychiatrist guilty of fraud in a drug study; the F.D.A. disqualification of another psychiatrist, for enrolling illiterate Hmong refugees in a drug study without their consent; the suspended license of yet another psychiatrist, who was charged with “reckless, if not willful, disregard” for dozens of patients; and, in 2004, the discovery, in a halfway house bathroom, of the near-decapitated corpse of Dan Markingson, a seriously mentally ill young man under an involuntary commitment order who committed suicide after enrolling, over the objections of his mother, in an industry-funded antipsychotic study run by members of the department.

And those, unfortunately, are just the highlights. The problem extends well beyond the department of psychiatry and into the university administration. Rather than dealing forthrightly with these ethical breaches, university officials have seemed more interested in covering up wrongdoing with a variety of underhanded tactics. Reporting in The Star Tribune discovered, for example, that in the felony case, university officials hid an internal investigation of the fraud from federal investigators for nearly four years.

I hope that the situation at the University of Minnesota is exceptional. But I know that at least one underlying cause of our problems is not limited to us: namely, the antiquated bureaucratic apparatus of institutional review boards, or I.R.B.s, which are supposed to protect subjects of medical experimentation. Indeed, whether other institutions have seen the kinds of abuses that have emerged at the University of Minnesota is difficult to know, precisely because the current research oversight system is inadequate to detect them. The current I.R.B. system of research protection arose in the 1970s. At the time, many reformers believed the main threat to research subjects came from overambitious government and university researchers who might be tempted to overlook the welfare of research subjects. As a result, the scheme put in place for protecting subjects was not a formal regulatory system but essentially an honor code. Under the I.R.B. system, medical research studies are evaluated — on paper — by a panel of academic volunteers. I.R.B.s do not usually monitor research as it is taking place. They rarely see a research subject or even a researcher face to face. Instead, they simply trust researchers to tell the truth, report mishaps honestly and conduct their studies in the way that they claim to be conducting them

These days, of course, medical research is not just a scholarly affair. It is also a global, multibillion-dollar business enterprise, powered by the pharmaceutical and medical-device industries. The ethical problem today is not merely that these corporations have plenty of money to grease the wheels of university research. It’s also that researchers themselves are often given powerful financial incentives to do unethical things: pressure vulnerable subjects to enroll in studies, fudge diagnoses to recruit otherwise ineligible subjects and keep subjects in studies even when they are doing poorly. In what other potentially dangerous industry do we rely on an honor code to keep people safe? Imagine if inspectors never actually set foot in meatpacking plants or coal mines, but gave approvals based entirely on paperwork filled out by the owners.

With so much money at stake in drug research, research subjects need a full-blown regulatory system. I.R.B.s should be replaced with oversight bodies that are fully independent — both financially and institutionally — of the research they are overseeing. These bodies must have the staffing and the authority to monitor research on the ground. And they must have the power to punish researchers who break the rules and institutions that cover up wrongdoing. Here at the University of Minnesota, we have reached a critical point. Two months ago, after two blistering external investigations, university officials finally agreed to suspend recruitment for psychiatric drug studies. Yet they still refuse to admit any serious wrongdoing. An honor code is a fragile thing. All the parts have to be in place: pride in the integrity of an institution, vigilant self-policing, a collective sense of shame when the code is violated and a willingness to punish those who break it. At the University of Minnesota, we have very few of those things. And so without sustained, relentless pressure from the outside, I am afraid we are doomed to more of the same.
I’ve used borrowed metaphors ["weak link in a chain", "house of cards"]  but they’re simply figures of speech that don’t seem up to the task. The care afforded to research subjects should be held to a higher standard than what’s called "treatment as usual," simply because there are unknowns in the equation. In this case, and in others [see above], it was decidedly less. That just can’t be tolerated. They’ve finally shut down the operation, and the Chief of Psychiatry has been removed from two positions. But this problem goes much higher into the administration of the Medical School, the University, and the higher levels of those in charge of conducting this Clinical Trial – the Principle Investigator, the Drug Company, and the CRO [Quintiles]. Human experimentation is a privilege, never a right, or routine, or casual. And most Clinical Trial participants won’t have a Carl Elliot et al to champion their rights. In this case, one card falling is only creating a scapegoat and not likely to fix anything. This is an Augean stable that needs a thorough cleaning, even beyond the borders of Minnesota…
Mickey @ 4:22 PM

not so proud…

Posted on Monday 25 May 2015

This is a follow-up to the last post [a narrative…]. I wrote Dr. Angell who pointed me to this editorial in the NEJM:
by Marcia Angell
The New England Journal of Medicine. 1999 341:752.

This week I succeed Jerome P. Kassirer as editor-in-chief of the Journal. Kassirer’s highly successful tenure was cut short after eight years when the Massachusetts Medical Society, which owns and publishes the Journal, decided not to renew his contract. Most observers were baffled by the decision, since the Journal was obviously flourishing under Kassirer’s superb leadership. In a joint announcement on July 25, Kassirer and Jack T. Evjy, president of the society, referred only to “honest differences of opinion between Dr. Kassirer and the Medical Society over administrative and publishing issues.”

Behind this oblique explanation lay a long-standing struggle between Kassirer and the society’s leadership over the latter’s ambitious plans to expand its role as a medical publisher, both in print and on line, by launching and acquiring new publications, repackaging the Journal’ s content for consumers, and entering into joint arrangements [“cobranding”] with various information-based commercial enterprises. Kassirer privately questioned the wisdom of many of these ventures, but what he strongly opposed in his capacity as editor-in-chief was the use of the Journal’s name to promote products for which he and his staff had no responsibility. To him, these activities threatened the Journal’ s credibility. To the society’s leadership and publishing staff, such leveraging not only was good business practice, but also furthered the society’s educational mission.

There were other, related disputes between Kassirer and the Journal’ s owner. The society for some time had talked of moving the Journal’ s editorial offices from the present location in Boston to the society’s headquarters in suburban Waltham. Kassirer resisted such a move, primarily because he felt it would lead to the incorporation of the Journal’ s staff into the larger organization and thereby threaten the Journal’ s quality and independence. There was also some concern that editorial autonomy might be eroded.

It is no secret that the other Journal editors and I were dismayed by the society’s decision to let Kassirer go, and that we shared many of his concerns about the use of the Journal’ s name to promote other products. The society’s action precipitated a crisis unique in the Journal’s 187-year history. There was even talk of a mass resignation by the editors, an event from which the Journal might never have recovered. Faced with the possibility of irretrievably damaging the Journal, both the society and the editors drew back from the brink. After intense discussions between the society’s leadership and the editors, Evjy and I issued a joint statement on August 4, which read, in part, as follows:
    The Massachusetts Medical Society and Dr. Marcia Angell, Executive Editor of the New England Journal of Medicine, are negotiating the terms of an agreement by which she will become interim Editor-in-Chief. We are committed to ensuring that the NEJM maintains its special position as the world’s pre-eminent medical journal. To that end, we have agreed on the following three principles:

  1. The Editor-in-Chief and her staff will continue to enjoy complete editorial independence and be fully responsible for content and editorial policy. The Editor-in-Chief will continue to confer on important editorial matters with the Society’s Committee on Publications and keep it informed, but neither that committee nor any other agent of the Society will have authority over content or editorial policy.
  2. The Editor-in-Chief will have authority over the use of the name, logo, and content of the New England Journal of Medicine, in print or any other form. Consumer versions of the content will also be subject to her approval or that of her staff. There will be no use of the name, “The New England Journal of …” for other products, as, for example, “The New England Journal of Cardiology.” Neither the logo nor the name of the NEJM will be used on other products or in marketing them, without the approval of the Editor-in-Chief, although such products may be identified as coming “from the publishers of the New England Journal of Medicine.”
  3. The Society recognizes the unique status of the NEJM within its publishing division and understands the concerns about moving the editorial offices to Waltham. No decision about moving has yet been made and none will be made without the full and active involvement of the Editor-in-Chief and her staff. In any event, no move will occur until the arrival of a permanent Editor-in-Chief.
  4. In view of our mutual commitment to these principles, we hope to reach rapid agreement on a detailed contract. [This has now been done.] In that case, Dr. Angell will serve as Editor-in-Chief until a permanent Editor-in-Chief assumes the post. Her present intention is to retire at that time. A blue-ribbon Search Committee, with representation from the professional editorial staff and the wider academic medical community, will be appointed as soon as possible.
The above principles provide a clear framework for a better relationship between the Journal and its owner, one that will permit the Journal to continue to thrive as the unique and independent institution it is. In agreeing to these principles, the leadership of the society recognized that the Journal, while legally its property, has a much broader “ownership.” For many in the academic research community, it is an invaluable and integral part of their professional lives; furthermore, much of the research published in the Journal is publicly funded, and its peer reviewers are all volunteers. The Massachusetts Medical Society bought the Journal for a dollar in 1921. Since then, it has for the most part exercised its stewardship with wise restraint and an awareness of the Journal’s larger constituency. I am optimistic that in the wake of the summer’s crisis, there will be a recommitment to this kind of stewardship. The society should take pride in such a resolution.

MARCIA ANGELL , M.D.
I’m not so proud of them as she apparently was back in the day…
Mickey @ 10:07 PM

a narrative…

Posted on Sunday 24 May 2015

In  wtf? for real… I was criticizing the editorial by Editor Jeffrey Drazen [Revisiting the Commercial–Academic Interface] and series by reporter Lisa Rosenbaum [Reconnecting the Dots — Reinterpreting Industry–Physician Relations, Understanding Bias — The Case for Careful Study, Beyond Moral Outrage — Weighing the Trade-Offs of COI Regulation] in the New England Journal of Medicine advocating the relaxation of their policy prohibiting authors from writing editorials or reviews that might benefit companies with whom they have a financial connection. That policy was introduced by former Editor Arnold Relman, an opponent of the increasing connections between the pharmaceutical industry and academic medicine. In 1980, he wrote an editorial about what he called the medical-industrial complex and the dangers of conflict of interests:
by Relman A. S.
New England Journal of Medicine. 1980  303[17]:963-970.
[partial text here]
Under his guidance, in 1984 the New England Journal of Medicine became the first journal to require authors to declare their financial connections with industry. Then in 1990, they added a policy that prohibited authors from writing editorials or reviews that might benefit companies with whom they had a financial connection. Arnold Relman was succeeded as editor in 1991 by Tufts Professor Jerome Kassirer who continued and perhaps extended this posture against the financial connections between academic authors and industry.

In wtf? for real…, I was lamenting current Editor Jeffrey Drazen advocating an easing up on this restriction on editorialists and review authors. I cited Relman’s 1980 editorial and a later one by his wife, Marcia Angell, in 2000 when she was editor for a time [Is Academic Medicine for Sale?] as the strong ethical stands I preferred. But, as Sandra Steingard pointed out in a comment, I had left out Jerome Kassirer who was also an advocate against commercial influences in the journal’s articles and the businification of medicine in general. In his editorial in 1996 written with Marcia Angell, then his Assistant Editor, they directly addressed this issue of editorialists and review article authors.

The editorial was prompted by publishing a review article of diet medications in the same issue as an article reporting an ominous side effect [pulmonary hypertension]. They discovered only after the issue had gone to press that the review’s authors had significant PHARMA financial connections.  Their editorial reaffirmed the policy from 1990:
EDITORIALS AND CONFLICTS OF INTEREST
by MARCIA ANGELL , M.D. and JEROME P. KASSIRER , M.D.
New England Journal of Medicine. 1996 335[14]:1055-1056.

…Since 1990 the Journal has had a policy that prohibits editorialists and authors of review articles from having any financial connection with a company that benefits from a drug or device discussed in the editorial or review article. This policy was an extension of our earlier policy, announced in 1984, that required authors merely to disclose their financial connections with industry. In the case of scientific reports, disclosure seemed adequate. Scientific reports are self-contained. They present original data, and readers can judge for themselves whether the authors’ interpretations are supported by the data. Editorials and review articles are different. They are not self-contained, and there are no primary data. Instead, editorialists and authors of review articles evaluate an issue on the basis of what they select from the literature as relevant. In the case of editorialists, their task is to use the study they have been asked to editorialize about as a springboard for an open-ended consideration of an important issue. It is expected that they will provide an unbiased and authoritative opinion about the matter. That is why we insist that editorialists have no financial ties to products that figure prominently in their work…

After the Journal instituted its 1984 policy requiring disclosure of conflicts of interest, other major medical journals adopted similar policies, but so far we stand alone in our contention that disclosure is not enough in the case of editorials and review articles. In our view, the increasing involvement of researchers in commercial activities makes this policy all the more important. Readers must be able to rely on editorialists to be disinterested. We hope that we will soon be joined in our policy by our sister journals.
Kassirer’s resistance to the intrusion of commercial influence ultimately came up against other forces in the halls of the New England Journal of Medicine which had just built a $50M headquarters building and was in the process of capitalizing on its time-honored brand in multiple other ways. By 1999, this conflict lead to him being fired:
New York Times
By LAWRENCE K. ALTMAN
July 27, 1999

The top editor of The New England Journal of Medicine is resigning under pressure in a dispute with its owners, the Massachusetts Medical Society, over the marketing of the journal’s prestigious name as part of an expanding publishing empire. Dr. Jerome P. Kassirer, 66, will step down as editor on Sept. 1 and then begin a seven-month sabbatical until his contract expires on March 31, he and Dr. Jack T. Evjy, the society’s president, said in interviews yesterday. Dr. Kassirer and Dr. Evjy declined to provide specifics of the dispute beyond saying it involved sharp differences in "administrative and publishing issues."

But other editors said the dispute reflects tensions generated as the society, like other traditional nonprofit medical organizations, seeks to generate more revenues to expand its influence in an increasingly competitive and political world of health care. Founded in 1812, the journal, based in Boston, has a circulation of 240,000 and is widely regarded as one of the world’s most rigorously edited scientific publications. In recent years, though, the Massachusetts Medical Society has added other publications for doctors and health newsletters intended for the general public. The society also recently built a plush headquarters in suburban Waltham and hired more staff members to deal with health and political issues.

Dr. Kassirer resisted this trend. "Does the society want to become a business?" he asked in his annual report last year. The report described ”a perceptible change in the nature of internal discussions about the Journal” and criticized what it called proposals for the society to ”brand” the journal by using its logo and name in creating new publications.

Dr. Kassirer has earned praise for his stewardship as the journal’s editor-in-chief since 1991. He was credited with appointing larger numbers of foreign scientists to the journal’s editorial board and attracting larger numbers of papers from foreign scientists. He also expanded the number of reviews and other features to lessen the journal’s esoteric nature and broaden its appeal to practicing doctors. Dr. Kassirer said he ”expected to stay a longer time, but it is not in the cards.” His resignation had nothing to do with the content of journal and he never felt constrained in expressing his opinion, he said, and "the medical society never tried to interfere"…

One of the journal’s main competitors, the Journal of the American Medical Association, is also searching for a new top editor. In January, Dr. George Lundberg was dismissed as editor for timing publication of a survey on attitudes toward sex during the impeachment hearings of President Clinton.
In his parting editorial, Kassirer said:
Goodbye, for Now
by Jerome P. Kassirer, M.D.
New England Journal of Medicine. 1999 341:686-687.

Because the officers of the Massachusetts Medical Society and I could not resolve our differences over administrative and publishing issues, they decided to seek a new editor-in-chief, and I leave the post in a few days…

I have been privileged to use the Journal’s bully pulpit. In my 70 editorials I have criticized for-profit medicine’s shortcomings, managed care’s flaws, the federal government’s misguided actions, and organizations that tried to undermine science for political motives. I have called attention to the progressive fragmentation of the health care system and the increasing number of uninsured persons. I have been critical of the American Medical Association and the National Rifle Association (several times each), the American Association of Health Plans, and the Health Care Financing Administration. I have been an advocate of high ethical standards and professionalism and have repeatedly called attention to financial incentives that might erode the integrity of physicians and threaten patient care. Very recently I offered a definition of editorial
That last line referred to his stand against the firing of JAMA Editor George Lundberg mentioned above. He was replaced by Assistant Editor Marcia Angell  as interim Editor, but she withdrew from the running as Kassirer’s replacement saying she was going to write a book on alternative medicine. It was during her one year as interim that she wrote the editorial mentioned in wtf? for real…:
by MARCIA ANGELL, MD
New England Journal of Medicine. 2000 342[20]:1516-1518.
As it turned out, Arnold Relman, Jerome Kassirer, and Marcia Angell all did go on to write books – but they weren’t just about alternative medicine:
Jeffrey Drazen, the current editor, replaced interim Marcia Angell in 2000:
New York Times
By LAWRENCE K. ALTMAN
May 12, 2000

Dr. Jeffrey M. Drazen, a leading asthma researcher at Harvard with strong ties to the drug industry, was named the editor of The New England Journal of Medicine here today. But the journal’s tough conflict-of-interest rules will prevent Dr. Drazen from writing certain articles and editorials for at least two years. Pledging to protect the integrity of The Journal’s information, Dr. Drazen, a professor of medicine at Harvard, said he would recuse himself from the editorial process for any papers submitted that relate to asthma or to nine major companies from which he has received research grants or consultation fees.

Dr. Drazen, 53, helped pioneer asthma drugs now taken by four million asthmatics worldwide. In today’s news conference, he strongly defended the need for doctors to work closely and carefully with the drug industry. He called the industry a powerful force without which basic research findings made through taxpayer grants from the National Institutes of Health could not be converted into new therapies to improve patient care and public health.

Last February, after an internal investigation prompted by articles in The Los Angeles Times, The Journal found that it had violated its own rules in publishing 19 articles by Dr. Drazen and other authors with industry ties. The Journal said the articles should have been written by scientists without such connections, but its editors blamed themselves and said Dr. Drazen had disclosed his industry support.

Asked today at the news conference about that episode, Dr. Drazen said that as The Journal’s new editor in chief he would hand over all manuscripts dealing with his specialty or products made by the nine companies to deputies "and make sure that they are on the agenda at a time when I do not come to the editorial meeting." In such cases, Dr. Drazen said he wanted "The Journal to be able to judge the science that comes in, if it is good or bad, without me having anything to do with it."

"I do not want to influence things in either a positive or a negative way,” he said. ”We want the good science and good information to get out there” in The Journal, which is one of the most influential in the world. Dr. Drazen, who will leave his Harvard post, will be the Journal’s third editor in chief in less than a year. His selection follows several years of turmoil between the editors of The Journal and its owner, the Massachusetts Medical Society, concerning the society’s increasing business ventures. Dr. Jerome P. Kassirer was fired as the top editor last summer because of conflicts with society officials over proposals to promote Web sites and create new specialty journals using The New England Journal of Medicine logo. In recent years, The Journal has become a huge source of revenue for the medical society, largely through increased drug company advertising. And the society has become heavily dependent on the Journal’s profits to maintain its new $50 million headquarters here…
I appreciate Sandra’s reminding us of Jerome Kassirer‘s place in this story. In my case, in 1999-2000, I was isolated from such things, aiming towards my own retirement. This narrative explains why I still saw the NEJM as it was in my youth ["What is this doing in the New England Journal of Medicine?"], and was so incredulous at reading Jeffrey Drazen‘s editorial and Lisa Rosenbaum‘s series. It also gives me a chance to acknowledge the yeoman’s efforts of Drs. Relman, Kassirer, and Angell in trying to push back against the capitalization and invasion of medicine by industry. It also explains Dr. Drazen‘s history and how this editorial and series must have been percolating for the fifteen years of his tenure as editor of the NEJM. There are mixed reactions to this series in the medical community and at large. I freely admit that my negative reaction is visceral. I can mount arguments with the best of them, but they come after the fact. I’ve lamented the growing medicine-as-business trend since medical school, and that lamentation has turned into a conviction. I don’t think I’m even capable of seeing the other side of this argument any more. There’s just been too much damage…

Mickey @ 12:39 PM

wtf? for real…

Posted on Friday 22 May 2015

see also:

In my Internal Medicine days, I read the New England Journal of Medicine from cover to cover every single week. I still pick it up in the doctor’s lounge and read it just like I used to. And when I changed to psychiatry, I lamented that there was no NEJM-analog. So my comment, "What is this doing in the New England Journal of Medicine?" in my last post about the Drazen/Rosenbaum articles [wtf?…], was as a long time reader.

Well, I reread the editorial and series this morning, and if anything, they were worse – bordering on polemics. I tried to cut them a little slack because they’re internists and not psychiatrists. Psychiatry has been on the leading edge of the kind of problems COI can lead to for decades. Maybe, I thought, they’re just naive and not so in touch with the kind of fire they’re playing with here. They’re civilians, whereas we psychiatrists are veterans – knowing first hand how this COI thing can grow into a metastacizing cancer. But then I was alerted to this story about the Vioxx debacle by Bioethicist Arthur Schafer [University of Manitoba]. Editor Jeffrey Drazen should be a veteran after Vioxx [see also in Wikipedia]:
Fortunately, rescue from company “spin” was at hand. Some alert scientists discovered that the VIGOR authors had failed to report several heart attack deaths in their NEJM publication even though they had supplied the correct data to the FDA… Even worse from the company’s point of view, the Vioxx deaths which had been suppressed from the NEJM article were deaths which occurred in patients with no history of heart disease. This fact kicked the legs out from under the company’s specious claim that only those with a history of heart disease were at elevated risk from taking Vioxx.

The investigators did not correct the scientific record. Their failure to do so was compounded when Dr. Jeffrey Drazen, esteemed editor of the NEJM, declined an opportunity to publish a letter submitted to the journal by independent scientists which would have alerted readers to the misleading nature of the data originally published. Years later, when the full extent of the harm done to tens of thousands of patients became undeniably clear, Drazen and his fellow editors at the NEJM justified their refusal to publish a timely correction with the intellectually [and morally] feeble excuse that it is the responsibility of authors, not journal editors, to correct data…

In sum, almost no one emerges with much credit from the saga of the Cox-2 inhibitors. The drug companies which massively marketed the drugs, both to doctors and directly to consumers, made billions of dollars; but, when the facts eventually emerged, the companies experienced a serious loss of public trust. Merck, in particular, is now facing a staggering number of expensive law suits. The company continues to insist that it took all reasonable measures to determine whether Vioxx carried undue cardiovascular risks and is defending its conduct in all of these law suits. Medical journals and their editors, in particular the NEJM and its editor Dr. Jeffrey Drazen, were seen by some critics as being incompetent at best and collusive at worst in what turned out to be a terrible human tragedy…


The University as Corporate Handmaiden: Who’re ya gonna trust?”, by Arthur Schafer in The Universities at Risk: How Politics, Special Interests, and Corporatization Threaten Academic Integrity, ed. Jim Turk. James Lorimer and Co, Toronto, 2008.

Note: Schafer’s chapter is well worth reading in toto for a thoughtful in depth look at this whole issue of the Corporate invasion of Academia.
It’s very discouraging to find an editor of the New England Journal of Medicine writing and commissioning a reporter to write something like this after the strong stand of editors who came before him [see we were warned… and these tainted articles…]:
by Relman AS.
New England Journal of Medicine. 1980  303[17]:963-970.
[partial text here]

The most important health-care development of the day is the recent, relatively unheralded rise of a huge new industry that supplies health-care services for profit. Proprietary hospitals and nursing homes, diagnostic laboratories, home-care and emergency-room services, hemodialysis, and a wide variety of other services produced a gross income to this industry last year of about $35 billion to +40 billion. This new "medical-industrial complex" may be more efficient than its nonprofit competition, but it creates the problems of overuse and fragmentation of services, overemphasis on technology, and "cream-skimming," and it may also exercise undue influence on national health policy. In this medical market, physicians must act as discerning purchasing agents for their patients and therefore should have no conflicting financial interests. Closer attention from the public and the profession, and careful study, are necessary to ensure that the "medical-industrial complex" puts the interest of the public before those of its stockholders.
[Update: see also comment re NEJM Editor Jerome Kassirer who was fired in 1999]
by MARCIA ANGELL, MD
New England Journal of Medicine. 2000 342[20]:1516-1518.

In 1984 the Journal became the first of the major medical journals to require authors of original research articles to disclose any financial ties with companies that make products discussed in papers submitted to us. We were aware that such ties were becoming fairly common, and we thought it reasonable to disclose them to readers. Although we came to this issue early, no one could have foreseen at the time just how ubiquitous and manifold such financial associations would become. The article by Keller et al. in this issue of the Journal provides a striking example. The authors’ ties with companies that make antidepressant drugs were so extensive that it would have used too much space to disclose them fully in the Journal. We decided merely to summarize them and to provide the details on our Web site.

Finding an editorialist to write about the article presented another problem. Our conflict-of-interest policy for editorialists, established in 1990, is stricter than that for authors of original research papers. Since editorialists do not provide data, but instead selectively review the literature and offer their judgments, we require that they have no important financial ties to companies that make products related to the issues they discuss. We do not believe disclosure is enough to deal with the problem of possible bias. This policy is analogous to the requirement that judges recuse themselves from hearing cases if they have financial ties to a litigant. Just as a judge’s disclosure would not be sufficiently reassuring to the other side in a court case, so we believe that a policy of caveat emptor is not enough for readers who depend on the opinion of editorialists.

But as we spoke with research psychiatrists about writing an editorial on the treatment of depression, we found very few who did not have financial ties to drug companies that make antidepressants. [Fortunately, Dr. Jan Scott, who is eminently qualified to write the editorial, met our standards with respect to conflicts of interest.] The problem is by no means unique to psychiatry. We routinely encounter similar difficulties in finding editorialists in other specialties, particularly those that involve the heavy use of expensive drugs and devices…
And by the way, "What is this doing in the New England Journal of Medicine?"
Mickey @ 8:39 PM

wtf?…

Posted on Thursday 21 May 2015

I know when I run into a blog post like this one that references no less than five articles without summaries, I frown because the author is implying that I should read all five of them. And that is what I’m implying. I’ve listed them chronologically as they’ve appeared, but you might do better to read Dr. Poses’ commentary on Healthcare Renewal first, before digging in to the four in the New England Journal of Medicine. When I read the first one, I found myself writing about the origins of Academe in ancient Greece [a contrarian frame of mind…]. I was looking back and forth at the Nizkor site [logical fallacies] the whole time. I decided not to write about Dr. Rosenbaum’s series until they were all published, because I wanted to use it as a lesson in fallacious arguments. And lo and behold, Dr. Poses beat me to it! But I’m glad he did because he found some I had missed, and he’s at his best when he’s in this mode. I’m going to leave that part to him, as a resident expert in that kind of analysis. You might as well go ahead and read them all. Everyone else is. And when you find yourself saying, "What is this doing in the New England Journal of Medicine?" Be comforted that you’re in a community of comrades who are asking the same question. And when you find yourself looking around for Dr. Rosenbaum’s COI declaration, all you’ll find is that she "is employed as a national correspondent for the New England Journal of Medicine.":
by Jeffrey M. Drazen, M.D.
New England Journal of Medicine. 2015 372:1853-1854.
May 7, 2015
by Lisa Rosenbaum, M.D.
New England Journal of Medicine. 2015 372:1860-1864.
May 7, 2015
by Lisa Rosenbaum, M.D.
New England Journal of Medicine. 2015; 372:1959-1963.
May 14, 2015
by Lisa Rosenbaum, M.D.
New England Journal of Medicine. 2015; 372:2064-2068.
May 21, 2015
Healthcare Renewal
by Roy Poses, M.D.
May 21, 2015
I’ll defer to Dr. Poses’ review of Rosenbaum’s logic. Earlier, I said that I couldn’t read Dr. Drazen’s editorial without having a contrarian inner voice constantly arguing with what I was reading [a contrarian frame of mind…]. And in spite of my attempts at reading what she had to say with an open mind, with each of Dr. Rosenbaum’s installments, that inner voice got louder and louder. She basically was proposing that the "moral outrage" at Conflicts of Interest was ingenuous, and reduced down to some kind of misguided politically correct anti-industry bias – a false and naive adherence to a utopian [but meaningless] standard. I was reminded of those Ayn Rand books like Atlas Shrugged where the brilliant movers and shakers are being held back by the self-righteous and mediocre masses. I’ve put the links up and it’s all on-line. I’m going to let it age for a day and reread it in the morning to see if it still looks like it does right now [which is pretty shameful]. And by the way, "What is this doing in the New England Journal of Medicine?"
Mickey @ 10:52 PM

tylenol deficiency and other headaches…

Posted on Wednesday 20 May 2015

There’s obviously more to say about Wunderink, but I wanted to stick in a few front burner items first:
The Globe and Mail
by ADRIANA BARTON
May. 17 2015

If serotonin is the “happy chemical,” then boosting our serotonin levels should keep depression at bay. After all, low serotonin brings on the blues, right? But the truth is, depression is not a serotonin deficiency. The idea that depression is caused by low serotonin levels is based on flimsy evidence dating to the 1950s. Pharmaceutical companies promoted the low serotonin story to sell Prozac and related antidepressants. They marketed a myth.

Today, the serotonin fallacy is as ingrained as the notion that drinking orange juice wards off a cold. Many of us still believe we are raising our serotonin levels to lift depression using wildly popular drugs known as selective serotonin re-uptake inhibitors, or SSRIS. But psychiatrists now say it is unlikely these drugs treat depression by simply increasing serotonin. While antidepressants help many patients, researchers have only a hazy idea of how they work. The consensus is that depression is a complex disorder with hundreds of potential underlying causes, said Dr. Roger McIntyre, head of the mood disorders psychopharmacology unit at the University Health Network in Toronto. “There’s really no scientific case to say that people who have depression have a deficiency in body and brain serotonin levels.”

The medical journal BMJ put the spotlight on the low serotonin doctrine in a recent editorial published in April and written by Dr. David Healy, a professor of psychiatry at Bangor University in Wales. Blockbuster sales of antidepressants such as Prozac are based on the marketing of the serotonin myth, Healy wrote. He added that pharmaceutical companies misled the public into putting too much faith in SSRIs.

Scientists never confirmed whether SSRIs raise or lower serotonin levels. “They still don’t know,” Healy said. Many of his peers suggest that Healy is not a respected figure in psychiatry, in part because of his stance that older tricyclic antidepressants are better than today’s Prozac-type drugs. His colleagues maintain that SSRIs are safer if taken in overdose than older antidepressants, and caution that patients should not switch medications based on Healy’s views. Nevertheless, most psychiatrists agree that depression is not a matter of serotonin levels being up or down. The role of serotonin in depression is best described as a “dysregulation” of the serotonin system, McIntyre said.

The serotonin system regulates aspects of behaviour, thought processes and mood. But it also interacts with other brain systems that may be involved in depression. Modern antidepressants block the re-absorption of serotonin in the brain. When researchers discovered that SSRIs helped depression in some patients, they concluded that low serotonin must be the cause of the disorder. But the assumption was no more valid than the notion that “having a headache means that your Tylenol levels are low,” McIntyre said. McIntyre described psychiatrists as being “guilty of exuberance” when they framed depression as a low serotonin problem.
David Healy’s editorial has gotten lots of play…
Maybe it was the just right time to put the Serotonin Myth to rest. Whatever the reason, it is long past due. And McIntyre’s line in this piece, ‘the assumption was no more valid than the notion that “having a headache means that your Tylenol levels are low,”‘ is an instant classic!

But on the darker side of the street:
AllTrials
18 May 2015
hat tip to Ferrell…  
The Guardian
by Sarah Boseley
18 May 2015

The long-fought battle for greater transparency in human drug trials is facing a major setback after a legal challenge against full disclosure from within the pharmaceutical industry. The Health Research Authority, which authorises trials and works to ensure the safety of patients taking part, has proposed that all drug trials must in future be registered. A judicial review has now been brought by a leading clinical trials company, challenging the plans for reform.

In the past, some drug companies have airbrushed out bad results by not publishing them, which could result in a drug appearing to work better and more safely than it does in reality. Many scientists, campaigners and health bodies have applauded the HRA’s proposals, which recently include a requirement on those running trials to ensure all previous studies they were involved in have also been registered – to try to bring historical data to light.

But Richmond Pharmacology, a company which conducts clinical trials on behalf of major pharmaceutical firms, has received permission to bring a judicial review of the HRA’s plans. Sense About Science, one of the organisations behind the AllTrials campaign for clinical trials transparency, says it is appalled that the issue is to be brought before the courts. “It is shocking that a company is using court action to try to stop transparency,” said Síle Lane, director of campaigns. “Hidden and unregistered trials are compromising patient care, and, rightly, causing public outrage.

“The HRA has really led the way with its proposals to check that clinical trials aren’t kept hidden during the trial approval process. Hundreds of members of the public, patients, researchers, doctors and pharmacists have told the HRA that this is exactly what it should be doing. They want the HRA to help right the injustice done to the thousands of patients who have taken part in clinical trials that have been kept hidden. I find it deplorable that one company is trying to stop that”…

The campaigners want to ensure that negative results are just as available as those from trials that succeeded in showing a drug was beneficial. From antidepressants such as Seroxat to the flu drug Tamiflu, it has been publicly argued that some drugs have worrying side effects or work less well than the published data suggests. Richmond Pharmacology said it was not at liberty to comment at the moment, because the case was in the hands of its lawyers.
Things never go as smoothly as we’d like, and I suppose that this kind of thing is to be expected, but it takes its toll. The Abbvie/Intermune assault on Data Transparency with the EMA was a setback that took some of the fire out of the EMA’s Program. And this feels like "here we go again" [Company Challenges UK Clinical Trial Transparency Rules].
Mickey @ 2:13 PM

comments…

Posted on Monday 18 May 2015

I was gone all day Saturday. I’m the BAR-B-Qist for our community, and it was a beautiful day for it. When I got up Sunday, there was an email from a Statistician with a ton of work for me to do. And then I read the comments and the emails about the comments, and my mood sunk. So I turned them off, because I had other important things to attend to. There was nothing wrong with the things people said, but it was the tone. It got contentious again. Let me be clear, I, 1boringoldman, don’t like that. One can make a point without doing it. I’m not going to moderate comments. The reason is simple. I don’t want to. If one of those obviously crazy comments shows up, I’ll deep-six it. But for regular commenters, I’ve got plenty on my plate as it is, and comment-cop just isn’t on my top ten list of fun things to do. So I turned the comments back on and am leaving it up to those of you who comment to make it safe. It’s your space – not mine. If you’ve got something to say to me in private, use 1boringoldman@gmail.com.

Mickey @ 10:07 PM

a contrarian frame of mind…

Posted on Monday 18 May 2015

"Over the past two decades, largely because of a few widely publicized episodes of unacceptable behavior by the pharmaceutical and biotechnology industry, many medical journal editors [including me] have made it harder and harder for people who have received industry payments or items of financial value to write editorials or review articles. The concern has been that such people have been bought by the drug companies. Having received industry money, the argument goes, even an acknowledged world expert can no longer provide untainted advice. But is this divide between academic researchers and industry in our best interest? I think not — and I am not alone. The National Center for Advancing Translational Sciences of the National Institutes of Health, the President’s Council of Advisors on Science and Technology, the World Economic Forum, the Gates Foundation, the Wellcome Trust, and the Food and Drug Administration are but a few of the institutions encouraging greater interaction between academics and industry, to provide tangible value for patients. Simply put, in no area of medicine are our diagnostics and therapeutics so good that we can call a halt to improvement, and true improvement can come only through collaboration. How can the divide be bridged? And why do medical journal editors remain concerned about authors with pharma and biotech associations? The reasons are complex. This week we begin a series of three articles by Lisa Rosenbaum examining the current state of affairs."
by Jeffrey M. Drazen, MD, Editor
NEJM 2015 372:1853-1854.

We are currently in the midst of a three part series of articles in the New England Journal of Medicine making the case that we’re overly concerned about medical experts having financial ties to industry – specifically, their being excluded from writing "editorials or review articles" in our medical journals. The series is introduced with an editorial [Revisiting the Commercial–Academic Interface] by editor Jeffrey M. Drazen, MD [excerpted above]. The thing is – I know from the outset that I’m guaranteed to disagree with what this editorial and the articles that follow are going to say before I read a word. We have taken such a massive hit in psychiatry along in this area that it’s hard for me to believe the NEJM is even publishing such a series. And when I read them, I find myself generating contrary-arguments, rather than following what the editor or author says with an open mind. I know I’m biased. But I come by that bias honestly. I already have a slant in my mind on this topic. For example, when Dr. Drazen writes…
    Over the past two decades, largely because of a few widely publicized episodes of unacceptable behavior by the pharmaceutical and biotechnology industry, many medical journal editors [including me] have made it harder and harder for people who have received industry payments or items of financial value to write editorials or review articles
I’m thinking…
    A few? You’ve got to be kidding me – they’re everywhere! And it’s not just editorials and review articles. How about all those RCTs that were really written by paid expert medical writers instead of the guest authors, the key opinion leaders, whose names appear on the by-line? Didn’t you read my last post? what Dr. Healy said "But perhaps an even greater shame will be seen to lie with the fact that, during this era, most publications on on-patent drugs in our best journals were ghost-written"?
Instead of thinking about my own bias, I’m wondering about Dr. Drazen’s bias. And earlier, when he gives this example…
    In the mid-1940s, Selman Waksman, a soil microbiologist, and his team discovered streptomycin, an antibiotic with action against the tubercle bacillus. Although he was able to show efficacy in the laboratory, Waksman realized that if his discovery was to be of value to the world, he needed a partner capable of manufacturing adequate amounts of the material under conditions that would make it suitable for use in humans. He therefore struck a deal with Merck to produce streptomycin for clinical use. Soon thereafter, the British Medical Association undertook a large randomized, controlled trial of streptomycin for the treatment of tuberculosis. The results, including a description of the utility of streptomycin and resistance to it, were published in the British Medical Journal. This partnership between an academic researcher and a drug company went on to alleviate substantial human suffering and should be a model for current behavior. Unfortunately, it is not.
I was thinking something like…
    But that’s not the rule. That’s an exception. Waxsman was one of those exceptions in science. He had ‘nailed’ the treatment of Tuberculosis. He didn’t have to sell us anything or refine any arguments.  We were eager to hear what he had to say. And we already knew about his industry connections. There weren’t any secrets or hidden motives to wonder about.
Editor Drazen mentions powerful groups that are encouraging greater interaction and cooperation between academic institutions and industry:
    The National Center for Advancing Translational Sciences of the National Institutes of Health, the President’s Council of Advisors on Science and Technology, the World Economic Forum, the Gates Foundation, the Wellcome Trust, and the Food and Drug Administration are but a few of the institutions encouraging greater interaction between academics and industry, to provide tangible value for patients. Simply put, in no area of medicine are our diagnostics and therapeutics so good that we can call a halt to improvement, and true improvement can come only through collaboration.
But once again, I’m thinking…
    That interaction and cooperation between academia and industry may well facilitate improvements in something. But what does that have to do with the question of bias when academics with a financial relationship to a company write a review or editorial about that company’s product in an academic journal? An academic can interact and cooperate without money changing hands…
Plato's Academy [Pompeii Mosaic]And so it goes as my bias generates contrarian counters to his arguments. Back in the days of the Academy in Ancient Greece, a time when they fell in love with the rules of argument and logic, they initially thought they could reach absolute truth with their debates. So they studied logic and cataloged wrong arguments as the fallacies. Then along came questions of bias, and motive, and later even unconscious motive. And the sacred olive groves of Plato’s Academe [and later Aristotle’s Lyceum] moved from the quest for dogmatic truth to becoming cloistered havens for skepticism and a questioning attitude. And Academia has been under siege ever since [with arguments not unlike the ones coming from this NEJM series].

In psychiatry, this kind of rationalizing away Conflicts of Interest has characterized the current era with disastrous results. We almost don’t have much we can call academia any more. When we look at RCTs, it’s hard to even locate an industry-funded Clinical Trial that isn’t ghost-written  with authors on the by-line with extensive financial connections to industry. The sacred olive grove full of scholars has been replaced with professional Key Opinion Leaders, professional Medical Writing companies, Clinical Research Organizations, and Pharmaceutical Marketing Departments.

I’m going to try to read the coming three part series with an open-ish mind, but this prequel feels a lot like the introduction to a polemic that will evoke a similar contrarian frame of mind…
Mickey @ 9:44 PM