a thorny problem, this one…

Posted on Monday 23 May 2016

Reading through Sergio Sismondo’s Ghosts in the Machine was confirming, validating my own impression that there is a  secretive commercially driven enterprise manipulating the processes by which we know about medications. I knew it was there, but I really didn’t know it was so ubiquitous, nor did I know it was a profession. But there were parts of his essay I just didn’t get. This was one of them:
Implicit in many of the exposes of ghostwriting in the medical science and popular literature is an assumption that ghostwritten science is formally inferior. Given the very high acceptance rates of ghost-managed papers, that assumption is questionable in general – though it may be right about important cases. Pharmaceutical company research, analysis, and writing results in knowledge. It is not different from other medical research, analysis, and writing in the fact that companies and their agents make choices in the running of clinical trials, in interpretations of data and established medical science, and in the messages they convey in papers and presentations. This point is straightforwardly suggested by STS’s longstanding commitment to symmetry. It is justified by the results of canonical studies that have shown how science is choice-laden. Thus, the work of pharmaceutical companies to produce research and place it prominently in medical journals is not merely a corporate use of the patina of science. It is science, though it is science done in a new, corporate mode.
It was one of those paragraphs you read over and over with the same question·mark look on your face. And apparently I’m not the only one [see Leemon McHenry’s Ghosts in the Machine: Comment on Sismondo]:
The commercial medical science that has created the ghostwriting industry is a corruption of science, and not merely as Sismondo puts it "science done in a new, corporate mode."
Which is what I think. Back to Sismondo, there was a part of Ghosts in the Machine that I really liked reading:
Everybody systematically connected with publication planning wants established formal rules of conduct. As sub-contractors, publication planners would like to reduce uncertainty, so that they can plan ahead and so that they can produce exactly the papers that will satisfy all of the different parties with whom they interact. Both publication planners and pharmaceutical companies want formal rules to guide and cover their work, to legitimize it so that its exposure does not amount to scandal…
In the course of life, I spent almost a decade as an educator/administrator. And as much as I enjoyed those years, there was one part I had no problem getting away from. It was hearing the question, "What is your policy about …?" To me, that meant "give me a rule so I’ll know how close to the line I can get without consequences" [and then the search for the loopholes began]. Here’s another solution that we might initially think we could agree with:
Bioethics. 2010 24[6]:273–283.

It is by now no secret that some scientific articles are ghost authored – that is, written by someone other than the person whose name appears at the top of the article. Ghost authorship, however, is only one sort of ghosting. In this article, we present evidence that pharmaceutical companies engage in the ghost management of the scientific literature, by controlling or shaping several crucial steps in the research, writing, and publication of scientific articles. Ghost management allows the pharmaceutical industry to shape the literature in ways that serve its interests.

This article aims to reinforce and expand publication ethics as an important area of concern for bioethics. Since ghost-managed research is primarily undertaken in the interests of marketing, large quantities of medical research violate not just publication norms but also research ethics. Much of this research involves human subjects, and yet is performed not primarily to increase knowledge for broad human benefit, but to disseminate results in the service of profits. Those who sponsor, manage, conduct, and publish such research therefore behave unethically, since they put patients at risk without justification. This leads us to a strong conclusion: if medical journals want to ensure that the research they publish is ethically sound, they should not publish articles that are commercially sponsored.

But then the doubts come creeping in. How would journals be financed? Industry is the only act in town able to finance trials. Where would physicians get information? package inserts? Who says the FDA Approval tells us enough to make clinical decisions? Who says the FDA is uncorruptable? And so on, and so on, and scooby-dooby-do…

A thorny problem, this one…
    May 23, 2016 | 3:37 PM

    My Firefox and Chrome fail on the Leemon McHenry link. This URL works for me (“#” instead of “&”): http://study329.org/wp-content/uploads/2014/09/Ghosts.Sismondo.pdf#page=4

    May 23, 2016 | 3:44 PM
    Thanks Antipaxos! It was a typo. Now fixed…
    James OBrien, M.D.
    May 23, 2016 | 4:17 PM

    He name dropped Popper and Kuhn. He is the modern day Paul Meehl. He doesn’t work too far from me.

    May 23, 2016 | 5:46 PM

    Post-1980 the Universities and Medical Centers are effectively, at least in some major senses, pharmaceutical companies of a kind. Not to mention that the survival of “fittest” academics (not infrequently those willing to be “visible authorities” who don’t raise too many difficult questions) has left us a somewhat hollowed out group of academicians when it comes to psychiatric clinical trial work.

    I believe we need to catalyze front line clinicians to move to at least a “I’m mildly perturbed and would not like to be subjected to this hollowed out literature for much longer, please” level of outrage.

    This is why I see Wagner’s nomination and election to presidency of AACAP as such a central issue. Schatzberg became president of APA before the bulk of the revelations about him came out. AACAP leaders nominated Wagner after over 10 years of such revelations and while they are still going strong. They are betting that nobody, including their members, cares enough about all of this for that to have been a mistake.

    It’s a litmus test of whether rank and file psychiatrists care about the selective representation of clinical trials that Wagner epitomizes.

    1bom, would you feel confidence in a clinical trial without any industry funding if the main person assuring transparency in the conduct of the analysis and representation were Wagner? Or an industry funded trial if the main person assuring transparency in the conduct of the analysis and representation were Carroll?

    May 23, 2016 | 6:23 PM

    I think my answer to your question is fairly obvious. But I’d like to amplify the question somewhat.

    Dr. Carroll is a researcher. His comments here, in his blogs on Healthcare Renewal, or in his publications are about the conduct of research, of trial techniques, of the details of analysis. They’re peppered with Odds Ratios, NNTs, statistical recalculations, diagnostic precision.

    I’m not as familiar with Dr. Wagner, but the commentary I see is about sales and marketing, not the processes that lead to those conclusions. For example, in an internal sales meeting for Paxil Study 329, she was talking about there being a marketing “window of opportunity” and how to capitalize on it [see the lesson of Study 329: the hurdles…]. Reading the documents in Jureidini et al, she was being consulted about which journal to publish in etc.

    So it’s a species difference. Dr. Wagner is a KOL in the modern sense of that word. They don’t do research. They talk about research results and other things…

    May 23, 2016 | 7:13 PM

    I think that Wagner’s nomination and election to president of AACAP presents an opportunity. To transition away from “contrarian” to “aspirational.” This to me is one of Goldacre’s greatest strengths.

    Stahl has clear reasons for having used the “scold” label. I truly believe that a focus on “ethics” is a grave mistake. It triggers the deeply ingrained “who am I to judge” reflex in most colleagues.

    To me the becoming president has opened up a new possibility. Because the choice was clearly made by leaders by this nomination to say that Wagner represents our best. What we aspire to be.

    It is time to become familiar with Dr. Wagner. 1bom, do you see a better time than the present? And, ask if we agree with our leadership that this is what we want our new generation to aspire to be. That question is NOT based on whether or not “the ethical concerns raised by the GSK lawsuit are not substantiated.”

    Is Dr. Wagner the model we want the next generation to follow? Do we want researchers with expertise or do we want visible experts? It’s time we press hard on how that difference is defined by much more than whether or not you’ve had a working relationship with pharma.

    The comments about placebo effect and informed consent in this https://www.industrydocumentslibrary.ucsf.edu/drug/docs/#id=qrmf0220 are telling and worth highlighting.

    Maybe it’s time to pitch a broader tent. And illustrate what we might want to aspire to in multidisciplinary work (academics, industry, clinicians …etc) and give examples of those academics who have provided that example. And, contrast that explicitly with the many examples that Wagner has provided.

    Because it’s about much more than relationship with industry vs no relationship with industry.

    It is very much about expert researchers vs visible experts. Because the ethos of hollow visible expertise persists even after the industry funding fades. And, we deserve to aspire to more than that.

    With or without relationships with pharma.

    Let’s stand up and say so.

    Placebo effect exists even if you’ve received psychotherapy.
    Even with informed consent clinicians are instilling a hope that the medication will be of help.
    Paroxetine’s short half-life was not an advantage to its side effect profile.

    What species do we hope to help thrive? To which do we aspire?

    May 23, 2016 | 9:54 PM

    “Placebo effect exists even if you’ve received psychotherapy.
    Even with informed consent clinicians are instilling a hope that the medication will be of help.
    Paroxetine’s short half-life was not an advantage to its side effect profile.”

    Sorry, these were in reference to Dr. Wagner’s comments about the placebo effect, informed consent, and paroxetine’s side effect profile vs fluoxetine.

    May 24, 2016 | 11:22 AM

    I would add that I think there are advantages and disadvantages to seeing all corporate controlled scientific endeavor as a corruption of the scientific endeavor.

    James OBrien, M.D.
    May 24, 2016 | 5:08 PM

    “I would add that I think there are advantages and disadvantages to seeing all corporate controlled scientific endeavor as a corruption of the scientific endeavor.”

    That’s a bit broad especially considering that corporate controlled scientific endeavors at Intel, Microsoft and Apple allowed you to type that message.

    Plus let’s not let government off the hook. Their nutrition science since WW2 has been about as far off the mark as you can be. And I won’t even get into how much they corrupt climate science.

    May 26, 2016 | 10:45 AM

    Re. Sismondo and “science done in a new, corporate mode”, there are 2 online book chapters that shed much light:
    1- from his introductory text on Science and Technology Studies: http://www.f.waseda.jp/sidoli/Sismondo_Introduction_STS_5.pdf
    2- from David Bloor, one of the field’s founders: http://people.stfx.ca/jcook/2010-11/bloorssk.pdf

    STS’s notion of science is very inclusive — something in the area of “What is it most sensible to believe about the world”. It includes far more than the specific kind of science that forestalls one’s Airbus plummeting. As a patient it’s a focus on the second kind that I want, even when that’s not yet available.

    May 28, 2016 | 9:10 PM
    James OBrien, M.D.
    May 29, 2016 | 6:07 PM

    Elsevier is the Goldman Sachs of academic publishing.

    That was not a compliment to them.

    June 5, 2016 | 2:35 PM

    Rank and file psychiatrists don’t seem to feel a great sense of loss at the impoverishment of our literature.

    While reflecting on this I was reading a post of a psychiatrist whose writings I enjoy/respect and came across this:
    “However, when I plug the raw data into 1 Boring Old Man’s table, (see also DIY Study Evaluation) I get: The trichotillomania study had a p value of 0.185, a Cohen’s D effect size of 0.433, and a 95% CI of -0.202 to 1.068 (In case it’s too hard to read). So there’s no statistically significant difference.”
    “Basically, the numbers are bad, and I only decided to include the spreadsheet as practice at evaluating a study.”
    “So now I ask myself, “Would I prescribe or recommend NAC?” Based on this post, I’d have to say maybe. I’d probably stick to the conditions I listed above.”
    In large part because it may be a relatively benign substance to give. But, at the same time there is little indication that one should be more confident in the reporting of adverse effects in these NAC publications than in others.

    This is NOT meant as a criticism of the reasoning of this particular clinician.

    I think what is hard to quantify, hard to imagine, is all of the more granular information (NOT just a binary “this medicine is good”, “this medicine is useless and harmful”) that we have lost through how so many clinical trials have been run, analyzed, and presented. What Psych Practice’s post communicates to me is that at the end of the day clinicians are largely left with clinical trial and error and over the past 2-3 decades clinical trials have become sapped of much of their usefulness to us.

    I think Dr. Carroll tries to speak to this, but for many junior clinicians and researchers (especially working with pediatric populations) we’ve become inured to the poverty of our literature.

    I think that those of us who do NOT view medications as either entirely effective or in-effective in a population (e.g., SSRIs for some adolescents struggling with significantly impairing depressive/anxiety symptoms, or stimulants for some adolescents struggling with significantly impairing focus issues) are most adversely impacted in our practice by this loss. Particularly if we don’t happen to have the years and volume of practice to have thousands of our own direct practice examples available to us.

    Though I also wonder if, in trying to cope with practicing in an environment of such a hollowed out literature, we’ve as a community also developed a blind spot in terms of how all this adversely impacts how well we are individually able to practice.

    Most clinicians don’t seem to feel that THEIR individual practice has been hobbled by the information that is absent in our literature as a result of the clinical research practices of the past 20-30 years.

    June 5, 2016 | 2:50 PM

    For instance this:
    At the end of the day, largely based on my clinical experience and that of my colleagues, there is no way that I am not prescribing stimulants as a mainstay of treatment for many individuals with significantly impairing presentations that appear consistent with an ADHD presentation.
    At the same time there is the feeling that there is information that could better inform my practice that is absent from the literature because the focus on the desired messaging endpoint has so strongly warped the design, analysis, and presentation of data from trials.
    At the same time, will add that the devaluing of direct clinical experience, the over simplification of EBM, is NOT specific to only pharma. For a Cochrane review to blithely suggest that methylphenidate is not an incredibly important mainstay of treatment for at least some individuals with an ADHD presentation flies in the face of so much directly clinical experience as to be almost absurd.

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