Ghostwriters of Science

by Henry on May 27, 2011

Via Randolph Fritz, a very interesting article about how extensive the pharmaceuticals ghostwriting industry is:

The planning companies are paid to implement high-impact publication strategies for specific drugs. They target the most influential academics to act as authors, draft the articles, and ensure that these include clearly-defined branding messages and appear in the most prestigious journals. … There are now at least 250 different companies engaged in the business of planning clinical publications for the pharmaceutical industry … Current Medical Directions, a medical communications company based in New York, promises to create “scientific content in support of our clients’ messages”. … n a flow-chart drawn up by Eric Crown, publications manager at Merck (the company that sold the controversial painkiller Vioxx), the determination of authorship appears as the fourth stage of the article preparation procedure. That is, only after company employees have presented clinical study data, discussed the findings, finalised “tactical plans” and identified where the article should be published. … “We’ve never done ghostwriting, per se, as I’d define it”, says John Romankiewicz, president of Scientific Therapeutics Information, the New Jersey firm that helped Merck promote Vioxx with a series of positive articles in medical journals. “We may have written a paper, but the people we work with have to have some input and approve it.”

I used to think that political scientists were lucky, in that no-one cared enough about what we had to say to try to suborn our reputations via dubious endorsements. And then I read about the Gadaffi and political science scandal …

{ 44 comments }

1

Straightwood 05.27.11 at 1:28 pm

The great invisible social science story of the modern era is the triumph of stealth in the engineering of professional opinion. Invisible to the radar of the dwindling number of guardians of truth, corporations have bought, bribed, suborned, twisted, bent, and perverted thousands of influential academics, public officials, and “public intellectuals.” Look at the ruins of the economics “profession” for abundant evidence.

The greatest triumph of this malign invisible movement is its normalization. An entire generation of knowledge workers now equates professionalism with material success. This is what Christopher Lasch termed the “betrayal of the elites,” but one cannot fault the elites entirely for pursuing greed over virtue. It is the stealth technicians who deserve the bulk of the blame. The slimy people who engineered the cunning, plausibly deniable schemes for warping the intellectual elite are the great villains of this story.

2

marcel 05.27.11 at 1:35 pm

A correction and 2 questions:

1) “scientific content in support of our clients’ messages” s/b

“scientistic content in support of our clients’ messages” or at least

“scientific [sic] content in support of our clients’ messages”

2)“We’ve never done ghostwriting, per se, as I’d define it”, says John Romankiewicz, president of Scientific Therapeutics Information, the New Jersey firm that helped Merck promote Vioxx with a series of positive articles in medical journals. “We may have written a paper, but the people we work with have to have some input and approve it.”

a) When did Mr. Romankiewicz become Webster (or Humpty Dumpty)?
b) Don’t the nominal authors typically “have to have some input and approve” what is written in their name?

3

William Timberman 05.27.11 at 2:38 pm

A mere three million bucks for all these rock-star academics? When you look at what Bill Clinton or Sarah Palin are/were? paid, you have to think of these professors as pikers.

The Gaddafi story reminds me of the time, years ago, when I overheard an antiquarian bookseller boasting that librarians could be bought for virtually nothing — contracts for carload lots of stuff cleaned out of the attics of Europe rarely cost him more than a dinner and a little flattery. This was, of course, back when many state university systems in the U.S. were expanding, and were flush with the money needed to buy themselves a proper accreditation.

4

J. Otto Pohl 05.27.11 at 2:47 pm

Academics have a long history of being stooges for the powers that be. This should not be anything surprising. Academics that annoy the powers that be often find themselves unemployed. See for instance the career of Norman Finkelstein.

5

Alex 05.27.11 at 3:02 pm

Title suggestion: “Ghost Writers in the Sci…”

6

Ginger Yellow 05.27.11 at 3:05 pm

“We may have written a paper, but the people we work with have to have some input and approve it.”

That sounds like a textbook definition of ghostwriting to me. In fact, most ghostwritten books probably have more input from their ostensible authors.

7

marcel 05.27.11 at 3:24 pm

A correction and 2 questions:

The Correction: scientific content in support of our clients’ messages should be either:

scientistic content in support of our clients’ messages

or

scientific [sic] content in support of our clients’ messages

The questions concern this passage:

“We’ve never done ghostwriting, per se, as I’d define it”, says John Romankiewicz, president of Scientific Therapeutics Information, the New Jersey firm that helped Merck promote Vioxx with a series of positive articles in medical journals. “We may have written a paper, but the people we work with have to have some input and approve it.”

1) Since when is Romankiewicz Mr. Webster (or Humpty Dumpty)?

2) Isn’t it the case that nominal authors always have some input (if only to tell the story) and have to approve what has been ghosted for them?

8

Empty inbox 05.27.11 at 3:31 pm

And yet …
Writing is a skill.

After all, the weasel phrase “Merck (the company that sold the controversial painkiller Vioxx)” didn’t write itself you know.

9

marcel 05.27.11 at 3:32 pm

The last comment need not be published (nor this one) since it duplicates one that I submitted a couple of hours earlier. I was curious about the moderation — hasn’t happened to me here before — so I thought to try again to see what was going on. I imagine that I pissed off Belle Waring, which I regret, esp. since I agree with several others in the comments from that post that it would be good if she posted more frequently.

10

Henry 05.27.11 at 4:20 pm

I can tell you happily that our moderation system is not guided by us. It has its own mind, and sometimes decides for reasons best known to itself to gobble up otherwise perfectly innocent comments. Typically, the only time when we intervene is when one of us checks on the queue of comments in moderation and liberates the captives. I can imagine circumstances under which one _might_ deliberately put a comment into moderation – e.g. if there was a borderline comment on a post by another CT author whom you suspected to be asleep b/c of timezone differences, and wanted to give him/her a chance to look at it before unleashing it on the world. But this would be pretty unusual. We don’t put comments into moderation as a punishment or suggestion of displeasure – when we really don’t like a comment we are quite upfront about it. But sometimes, comments may languish depending on whether one of the two or three busybodies who make it our business to keep an eye on the queue check in or not (holiday weekends may be bad times to post here …).

11

Billikin 05.27.11 at 4:39 pm

“We’ve never done ghostwriting, per se, as I’d define it”, says John Romankiewicz, president of Scientific Therapeutics Information, the New Jersey firm that helped Merck promote Vioxx with a series of positive articles in medical journals. “We may have written a paper, but the people we work with have to have some input and approve it.”

Hmmm. Does medical ethics not require that **all** authors be credited in published papers?

12

roac 05.27.11 at 4:51 pm

Touching to envision the freed comments emerging into the digital sunlight, singing O welche Lust . . .

13

Glen Tomkins 05.27.11 at 5:12 pm

Less here than meets the eye

However marginally these drug company efforts may end up influencing physician practice, patients shouldn’t have to worry that that practice is for sale, so, yes, it is a disgrace that the profession tolerates this crap, and that the industry is allowed to do this.

That said, the influence really is quite marginal. Now, there’s gold in them thar margins, in the sense that the medications still under patent that are pushed in this manner are priced so that very marginal increments in sales mean a lot, so there is ample incentive for the drug companies to engage in this sort of practice, no matter how little it effects practice overall. But the effect on the cost of medical care, or its quality (the idea that such techniques will get physicians to prescribe the wrong medications), is quite marginal. Big Pharma gets to gouge us because it is part of the overall health care cartel, because we allow cartels in health care, not because it uses these means to wangle marginally more use of expensive new drugs than is warranted by clinical necessity.

Dramatic cures tend to get all the attention, and dominate how people (even professionals, who ought to know better) tend to think of medicine. But mostly we are only able to fiddle around the margins of disease, get some marginally better result than not doing anything, than using Christian Science instead of seeking medical attention. Of course, when the stakes are life and death, even quite marginal improvements are worth pursuing, so, no, using Christian Science instead of medicine doesn’t make sense anymore (as it did up until a century or so ago).

It’s not as if any of these paid shills, no matter what his or her academic credentials, or however they dress up their opinions, could make more than a very marginal difference in clinical practice. Clinicians are going to respond dramatically only to evidence of dramatic differences in outcome. If that evidence exists, the issue will never get to the RCT (randomized controlled trial) level, never get to the point of generating evidence so complicated that ordinary clinicians will need an expert to sort through it for them. It’s only ethical to randomize treatments where there truly is no already existing reason to think that either treatment is better. We’ve never had an RCT on anti-biotics for bacterial meningitis, and never will. All we ever had on that question were a few case series, a very weak study design. Not that clinicians waited for even those to be published before starting to use antibiotics for bacterial meningitis. Evidence of differences in outcome so dramatic that all you need is a case series and historical controls, doesn’t need an expert to interpret and change everyone’s practice overnight. IN contrast, if the differences in outcome are so weak that you need some RCT that found some marginal difference in one statin over another to prove the point, only a marginal few clinicians are ever going to pay heed, whether the expert is some shill or a truly disinterested expert.

14

chris 05.27.11 at 5:24 pm

The greatest triumph of this malign invisible movement is its normalization. An entire generation of knowledge workers now equates professionalism with material success.

Yes, this explains why they revere Lysenko for his successful advancement of his career and hold Galileo in contempt — he didn’t even have enough sense to bend his results into a shape that would please the powers that be.

Not that there isn’t some basis for your concerns, but “triumph” is a bit of an overstatement. Even in economics some still hold to the old values of evidence and reason — they’re just not as likely to have prestigious positions in well-funded institutions as the sellouts.

I think the problem is more that the *larger culture* values material success too highly, and therefore assumes that the most materially successful experts must be the best ones (when, for the reasons you outline, they’re more likely to be the worst).

15

b9n10nt 05.27.11 at 5:38 pm

“We’ve never done ghostwriting, per se, as I’d define it”… “We may have written a paper, but the people we work with have to have some input and approve it.”

God I want to hear that said by Will Ferrel at the pool party scene of Anchorman while talking to the blond.

16

roac 05.27.11 at 5:44 pm

Glen, what you say seems reasonable enough (though the people running the pharma companies must think this practice pays off, or they would stop doing it). But the question is, why are people who are demonstrated to have sold any integrity they ever had allowed to keep publishing and drawing their paychecks?

To put it in a medical metaphor: If this particular foreign organism is only mildly pathogenic, that is cause for relief. But the failure of the immune system to respond appropriately suggests that something is drastically wrong, and if we don’t fix it we may not always be so lucky.

17

Glen Tomkins 05.27.11 at 10:20 pm

Well, as I said, the marginal nature of the effect on practice is absolutely no reason to not ban it. You can’t expect the average patient to know enough about how medicine works to understand that the effect is marginal, and no patient deserves to contemplate the spectacle of the standard of care, on which his life may depend, even apparently for sale.

But the marginal effect on practice is why it is tolerated, why most physicians are rather blase about it.

Personally, the reason I started, some years ago, categorically refusing to partake of any of the little bennies (Free food! You risk getting kicked out of the AMA if you refuse free food, however .) and tchotchkes the drug reps make available, is that they get to write this stuff off as a business expense, then jack up the prices they extort from widows and orphans for their products.

As for the idea that academic integrity is somehow threatened, well I won’t argue against that idea. I thoroughly agree. But I’m rather old-fashioned in that respect, coming as I do from a long line of physicians who practiced back when you couldn’t make any money at it, but you did it for the prestige and place in society the avocation would bring the family, a family that had to have other means. Well, nowadays you can make quite a bit of money at it, so there’s that temptation. And we do live in a society in which the ability to make a lot of money is systematically confused with competence, and the failure to make a lot of money is confused with lack of intelligence and/or energy and ambition.

Now, in that milieu, merely academic physicians don’t really rank too high in any sort of hierarchy, because they don’t make much money, not like sub-specialty surgeons. And ordinary practitioners don’t have any particular reason to feel betrayed if an academic has found some sweet deal with a drug company, because most practitioners don’t really pay much attention to the literature. Please don’t be shocked. As I explained in my first post, anything that needs an RTC to prove it probably is an effect too small to be clinically significant. This habit of physicians in ordinary practice drives the Evidence-Based Medicine people to distraction, but frankly, all the important issues in medicine are resolved prior to the quantitative methods that you need an MPH or the academics to sort through. Yes, MDs should all get MPHs, and Epidemiolgy is way more relevant ot medicine than, say, organic chemistry, but, frankly, neither effects practice much.

18

roy belmont 05.27.11 at 11:48 pm

Right alongside the growth of precision-engineered informatical opinion-creation tools is the schlub-crescendo of democracy-as-human-project-central.
Which, to me, on the face of it, generally, as far as I can see anyway, is a little odd.
Because, as my uncle Hiram once said to me, “O’course, Roy, if we kin create yer pinions, we aint gonna give much of a shit who or what y’all’re gonna tryna vote fer, to, or at.”

19

roac 05.28.11 at 12:54 am

Thanks for the insight.

I would be interested in your thoughts on the direct marketing of prescription drugs to end users. Or, as a bumper sticker I once read put it, “ASK YOUR DOCTOR IF GETTING YOUR MEDICAL ADVICE FROM A TV COMMERCIAL IS RIGHT FOR YOU.”

20

Barry 05.28.11 at 12:13 pm

Chris: “Not that there isn’t some basis for your concerns, but “triumph” is a bit of an overstatement. Even in economics some still hold to the old values of evidence and reason—they’re just not as likely to have prestigious positions in well-funded institutions as the sellouts.”

Which does the job quite nicely. If the ‘elite’, well-funded and prestigious departments are full of hacks and liars, then it really doesn’t matter what good work is being done in State U, or Small Unknown Private College.

21

David Kaib 05.28.11 at 4:05 pm

While this is considerably more disturbing than the more run-of-the-mill kind of ghost writing, I’m struck by why we tolerate ghostwriting at all. Why are we supposed to pretend that presidential aspirants and sports stars and tv personalities are really writing the books that are issued under their name? Why is it unacceptable to admit that an institution is responsible for a piece of writing rather than the person who is the figure head for that institution? My guess is that in your average book store the non-fiction section is awash with ghost written works.

More on point, thank goodness we’re decided to turn life and death decisions into profit making opportunities.

22

deliasmith 05.28.11 at 11:27 pm

Hmmm. Does medical ethics not require that all authors be credited in published papers?

To the contrary. Most medical journals require that ONLY the people who took part in the research are credited. In other words they forbid the crediting of mere writers. And though they can be slack or worse about who’s in the researchers category (dead people sometimes crop up), they are assiduous in keeping out the writers.

23

Roger 05.29.11 at 2:22 pm

“That said, the influence really is quite marginal.”

Glen – I assume from your comments that you are a physician. My experience as a practicing physician and clinical researcher with some experience in drug development is different. These kinds of things do make a real difference in physician prescribing habits. Its not just the ghost-writing, its the whole use of academics as “opinion leaders” as part of a marketing strategy. Its not difficult to find examples of this opinion leader approach substantially enhancing revenues.

Parenthetically, there are many examples of RCTs having a substantial effect on clinical practice. Its correct that there were never RCTs for antibiotic treatment of bacterial meningitis, but there have been RCTs of vaccines for bacterial meningitis, and the latter have had a large beneficial impact.

24

The Raven 05.29.11 at 5:25 pm

Glen, saying this doesn’t matter because practicing doctors largely don’t take current research into account is somehow not reassuring.

More food for us corvids, though!

25

Salient 05.29.11 at 6:11 pm

“We’ve never done ghostwriting, per se, as I’d define it”, says John Romankiewicz, president of Scientific Therapeutics Information, the New Jersey firm that helped Merck promote Vioxx with a series of positive articles in medical journals. “We may have written a paper, but the people we work with have to have some input and approve it.”

That’s the most awesome sentence pairing ever to appear in a quotation, ever. “We’ve never done ghostwriting as I’d define it. We’ve done ghostwriting as you’d define it. … Next question?”

… “Not to my knowledge, no, I’ve never misused the phrase ‘per se’ as I’d define it. I’ve misused ‘per se’ as you’d define it. … Next question?”

26

Randolph 05.29.11 at 8:34 pm

I think it does matter.

For one thing, research guides teaching, so practitioners now in training will be affected.

For another, the marketing content in research pushes out other sorts of research, so, over the long term, the published literature comes to be dominated by marketing studies. This reduces the chance of non-marketing research being published. Diagnosis in internal medicine is an area that might benefit greatly from research attention and is not a center of research interest for pharmaceutical or medical technology firms.

Then, too, there is the illusion of control that comes with action; it’s why surgeons end up believing in surgeries that turn out not be effective. Without scientific study, doctors rely on experience and intuition, and even very smart, competent people do not have perfect intuition.

Now, in my own field, building science, most research is funded by manufacturers. This has not been so bad but, for instance, it is hard to get attention paid to alternative energy. Most research in that area is government-funded and the right wing keeps cutting the funding. Also, sometimes the manufacturers research misses major things. IIRC, over 50% of brick veneer walls built (I think the actual number was much higher) in Canada since 1970 or so failed–the underlying connectors rusting and the bricks pulling loose. This was fairly easy to predict. The Canadian climate is brutal; if there is a way for the weather to get inside a wall, that weather will get in. Bricks are pourous and brick walls have many joints. Careful design and study are required to see that water the underlying steel. But the research work and the design corrections weren’t done until a great many buildings had been clad in those materials. And still, Google for “light steel brick veneer failure canada” does not bring up a summary of the problem in the first two pages, though it does bring up marketing literature from the Canadian Sheet Steel Building Institute. If one digs around one can find Cowle’s summary report. The keywords I used were “Alderney Manor wall failure”. They key point in Cowle’s report is, “Even minor design and construction errors in a steel stud wall can lead to structural failure. This is because the steel stud system is much more vulnerable to moisture damage.”

In terms of research, if building science was independent of the construction materials industry, I think there would have been a better chance of catching the problems before poor wall details and construction became widespread. As it was, there was a great deal of expense and difficulty.

So, yes, I think it matters a great deal.

27

Randolph 05.29.11 at 8:35 pm

“that water the underlying steel”

er, “that water does not corrode the underlying steel”

28

derrida derider 05.30.11 at 2:01 am

“The art of medicine consists in amusing the patient with nostrums while waiting for nature to heal him” – Voltaire

Glen’s right about the marginal effects of most of the profitable treatments, but I don’t at all agree with him that there is only a marginal cost in this choice. There is a huge cost to this whole corrupting marketing apparatus in ineffective, overpriced and even directly harmful treatments.

The biggest costs are not direct, but opportunity costs . Every dollar spent developing, getting approval for, and then pushing a patented minor variation of an old drug is a dollar not spent on more effective interventions. Every time a patient is put on an unproven treatment they are denied a proven treatment.

Some time spent fossicking around the Cochrane Collaboration website is, IMO, a must for any clinician, and indeed for any patient.

29

Glen Tomkins 05.30.11 at 6:00 am

The Raven,

You will have to stand in line behind the entire Evidence-Based Medicine movement in your concern that practicing physicians mostly ignore current research. My take is that while they and you undoubtedly have a point, it’s not the huge scary issue you might think at first glance that supposed men and women of science don’t pay much attention to scientific research.

The reason for the ignorance, and why that ignorance isn’t really critical, is that the scientific literature in medicine, at least these days, confines itself to reporting the results of clinical research, and that research, and the quantitative methods by which it is conducted, don’t come into play until after all the important issues are settled. You can’t count to apply your quantitative methods until you’ve already decided what you’re counting, until you can distinguish your apples from your oranges. But it turns out that that’s the key step, that’s what takes all the skull sweat, deciding, at the profession-wide level, on a nosology, a list of diseases and their defining clinical characteristics, and at the indvidual patient level, on a differential diagnosis, deciding which, if any, of those defined clinical entities your patient has, or might have with a high enough probability to make it worth while ruling that diagnosis in or out. All of that is pre-quantitative, a matter of gestalt and pattern recognition, with no help from numbers until you’re so close to a diagnosis you don’t need algorithmic help anymore anyway.

Take, for example, prostate cancer. Now, given that this disease is now detected by way of a blood test, and then staged by way of biopsy material sectioned, stained and examined under a microscope, these technological trappings mislead many people, including practitioners, who ought to know better, into imagining that we are in some Physics-like environment where all the answers are as well-defined and clear as the pathology reading of the biopsy specimens. But the technology only tells you prostate cancer vs not prostate cancer, not what to do about prostate cancer. Trial and error had given us an answer to the question of what to do about prostate cancer — remove the prostate. But because that answer was based on empirical observation of what happened if you did vs did not remove the prostate in response to clinically-discovered prostate cancer, and was not built from any deep understanding of how prostate cancer actually works, that answer did not survive the new blood test, the PSA, which detects prostate cancer at a rate higher than it was observed in the past to ever become clinically apparent. It is conceivable that that means that prostate cancer is becoming dramatically more common, but that seems very unlikely, and most people believe it means that the PSA, while detecting prostate cancer that is fated to kill the patient unless his prostate is removed, also detects quite a bit of prostate cancer that will never go anywhere, will never cause the patient the least harm. It is no longer at all clear that whacking out the prostate when prostate cancer is discovered by way of PSA is the right thing to do, because such whacking puts at risk all sorts of plumbing and wiring that run close to the prostate. This question that has arisen because the PSA redefined the nosology, made it necessary to distinguish clinically-discovered from PSA-discovered prostate cancer, is not amenable to answer by quantitative methods. To do an RCT on the question would involve randomizing some men with PSA-discovered prostate cancer to no treatment, when we do not know that this will not condemn them to a death that prompt prostatectomy would have spared them. That won’t be ethical until clinical experience, the same sort of empiricism that taught us that prostatectomy was necessary for clinically-dscovered prostate cancer, tells us that it the surgery isn’t necessary in all cases of PSA-discovered prostate cancer. At that point, yes, I’m sure people will jump in with RCTs, but they will only serve to put a fine point of what exact cutoffs of pathology results (“how much” cancer is present, how high the Gleason Score is) and PSA level dictates which approach, not to tell practitioners that watchful waiting is or is not appropriate for low scores. That question has to be settled, at least roughly, before we can do an RCT.

Just because most practitioners don’t pay much attention to the literature, doesn’t mean that they are not responding to empiricism, not following an appropriate scientific method. It just means that in medicine, the most important empiricicm happens before we can trundle in the quantitative methods that the literature traffics in. Those methods only put a fine point on what we already know, and ususally that point is so fine as to be clinically insignificant, no matter how statistically significant.

Medicine isn’t physics, though they both started out in the same proto-science mishmash. The latter got to choose what it studied, and chose only phenomena amenable right out the gate to quantitative methods. Medicine will never get to choose its subject matter based on its ready quantitative digestibility, it gets its subject matter presented to it by patients, and has to come up with the best answers that empiricism allows under those conditions. So medicine has followed a more devious and obscure path since the two separated.

That said, I personally line up with the Evidence-Based folks. I have my MPH. But frankly, I find the extra level of critical thought about the medical literature it opens up useful mainly as a corrective to any tendency to set too much store by anything in the literature. I can’t be bamboozled into the false attribution of practice-changing findings to every study that rolls down the pike because I have the critical tools, while most of my colleagues cannot be so bamboozled because they don’t bother to read the literature — but the result is largely the same.

30

Roger 05.30.11 at 3:30 pm

Glen – its precisely because most physicians don’t pay critical attention to the literature that the “opinion leader” approach, including ghost writing, is an effective marketing strategy. Why worry, for example, about absolute versus relative risk reduction when you can read a slick review article published in an industry sponsored supplement to a prestigious journal that lays out a simple flowchart or set of guidelines for treatment?

31

Thomas Jørgensen 05.30.11 at 5:06 pm

The more I hear about the pharmacutical industry, the more convinced I get that we probably ought to burn our entire IP regime in this area to the ground, then salt the soil where it grew. Ultimately, the biggest buyer of all the products of pharma is the goverments of the world, so what we are currently doing is paying both for the research and for the marketing that distorts the research out of public coffers, which is simply madness. It would be far more efficient to void all patents from all medicine, and simply foot the bill for medical research directly out of the taxpayers pocket. Do it right, and it should be possible to realize both cost savings, a bigger total research budget for medicine and far, far higher standards of medical research. Among other things, publicly funded research might be more oriented towards cures than symptom treatments..

32

bianca steele 05.30.11 at 8:09 pm

I’ve never quite understood what evidence-based medicine is, or how it avoids “empiricism” in the bad sense. What is it opposing? Is it aimed at policy-making groups and medical school faculties, or at individual MD’s and NP’s? Is it aimed at changing education or current practice? Does it ask doctors to form new theories based on evidence (in place of what?) and follow those experts who’ve formulated those theories , or does it ask them to follow individual studies as they come out?

33

Glen Tomkins 05.31.11 at 5:15 am

Roger,

Because of the monopoly protection we give drug makers under patent protection, you don’t have to shift the prescribing habits of many practitioners at all, or very much at all, in the direction of some new med, to make it worthwhile to the drug companies to go through their whole drill — the opinion leader journal articles and CME presentations, the CME trips, food and tchotchkes, etc., etc. But I can’t point to a single instance of this sort of opinion leader, the drug company shill, having more than a very marginal effect on practice.

Now, since there is not any good at all to balance this very small harm, yes, we should still go ahead and end these practices. I think other harms, particularly the harm to patient confidence created by this circus, are even greater than the very small harm of the very small untoward effect on practice, but in the absence of any good created by allowing Big Pharma to do any marketing at all, they should be prohibited from all such.

Now, if we agree on the practical outcome, then there is perhaps little point in arguing over the rationale for that desired outcome. I only maintain my point about the marginal nature of the influence from these opinion leaders and their sometimes ghostwritten material, for two side reasons — to explain the blase reaction most practitioners have to this circus, because they think of it as something quite marginal, and to avoid falsely inflating this particular circus into an appreciable, much less major, cause of the money and quality problems that medicine is having right now.

To find an example of opinion leadership that actually did cause a more than marginal untoward bias in practice, you have to turn from these drug company shills to opinion leaders organized enough to actually change practice within the profession on a large scale. For many years, most of the relevant professional societies urged estrogen replacement therapy as a cardioprotective for post-menopausal women, despite the best evidence for this at the time being cohort studies that showed RRs no better than 1.3:1. The rule of thumb is that, because of the potential for large imponderable biases inherent in observational studies, you don’t even begin to think about attributing causality until you get past 2-3:1. To have something with only a 1.3:1 touted as the basis for a definite treatment recommendation was a much clearer distortion of usual standards than anything I’ve heard these shills advocating. And unlike their efforts, the recommendations from the wide chorus of eminently respectable and well-regarded professional groups who backed ERT as a primary prevention for all post-menopausal women, had a huge impact on practice for over a decade. Of course, when they eventually did the RCT on the question, that 1.3:1 disappeared, as everyone who understood the weakness of observational studies should have expected.

The great ERT fiasco is what I use as the benchmark for opinion leadership in medicine gone astray, and by that benchmark, the shills are small potatoes. That should be seen as reassuring for the basic soundness of the empirical approach of the average clinician. They rely more on consensus than clinical research evidence, so they don’t pay much attention to individuals waving bits of research at them, whether those individuals are shills or otherwise. And consensus formation is beyond inappropriate influence except by understandable biases such as those that caused the consensus of opinion leaders to get ERT wrong, idealistic biases such as a desire to promote primary prevention, and Women’s Health, etc.

34

Gustav 05.31.11 at 7:49 am

Check out this paper: Sergio Sismondo, “Ghost Management: How Much of the Medical Literature Is Shaped Behind the Scenes by the Pharmaceutical Industry?,” PLoS Med 4, no. 9 (2007): e286.

35

Gustav 05.31.11 at 7:53 am

…. and the work by Ben Goldacre.

36

Hidari 05.31.11 at 10:26 am

‘I’ve never quite understood what evidence-based medicine is, or how it avoids “empiricism” in the bad sense. What is it opposing? Is it aimed at policy-making groups and medical school faculties, or at individual MD’s and NP’s? Is it aimed at changing education or current practice? Does it ask doctors to form new theories based on evidence (in place of what?) and follow those experts who’ve formulated those theories , or does it ask them to follow individual studies as they come out?’

You may well ask. While in the absolute broadest sense of the word I am in favour of ‘Evidence Based Medicine’ you really do have to have an extremely sophisticated view of what the word ‘evidence’ actually means, which most proponents of EBM simply do not have. For example, looking through the literature, there is a widespread belief (and the word belief is entirely appropriate here) that there exist simple, objectively knowable phenomena called ‘facts’, that these facts can be accessed by anyone by epistemologically simple activities, that these facts are objective and do not need a context to be understood, and so on. Without going back to the Sokal hoax, all these beliefs are, in actual fact, highly questionable.

Moreover, even in the work of Ben Goldacre, who I admire, there is a highly romantic view of science. For example, the implication of Goldacre’s work is that ‘science’ was, so to speak, ‘pure’ before being ‘sullied’ by Big Pharma and post-industrial capitalism generally.

But when were scientific theories and beliefs ever wholly separate from the societies in which they were held? And when were broader issues of gender, ethnicity and power ever wholly separate from the process of scientific enquiry?

And no that doesn’t mean that I believe that all science is a ‘social construction’ or anything like that before anyone gets smart.

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The Raven 05.31.11 at 3:11 pm

Dr. Tomkins, your argument is probably very much like the arguments deployed against the work of Semmelweis and Pasteur. Doctors of that period felt that their clinical intuition trumped the statistical and microbiological evidence.

Hidari, this is a big part of the rationale of evidence-based medicine. Doctors are subject to “illusions of control” (a technical term in psychology) which leads them to believe that their interventions are effective when the results are random, or even negative. It has happened multiple times in the history of medicine that some ineffective, or even dangerous practice, is widely believed by medical professionals to be effective. Sometimes this can contribute to inaction, as well as action. In Semmelweis’s time, doctors refused to believe that their own unwashed hands were causing childbed fever, since they believed their interventions were healing. Doctors even argued that Semmelweis’s valid claims were unscientific, since they could not see a a mechanism by which his aseptic practices worked. In our own time, unnecessary surgery is still a problem. It is less than a problem than 30 years ago, but this is largely due to pressure from insurance companies, and that based on actuarial evidence.

Humanity is still at the dawn of scientific medicine. The wide acceptance of aseptic practices is only 100 old and their incomplete practice is still a problem. There is still much blundering through illusion and forgetfulness. Dr. Tomkins, you argue for clinical intuition above technical evidence. The advocates of evidence-based-medicine argue just the reverse. I say both are valuable, and it is illusion and error to give either sort of knowledge too much weight.

Which, returning to the original subject, means I regard the filling of the medical journals with well-buttressed marketing literature as a very serious problem.

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Tim Wilkinson 06.01.11 at 9:49 am

Ghostwriting – jockeying for headlines and putting spin on trial results (don’t all new drugs go through CRTs as part of licencing?) is just one symptom of drug companies expending a great deal of effort (and deadweight spending) in trying to influence doctors to prescribe their drugs, esp new and relatively expensive ones. (In the UK, NHS doctors have to prescribe generics where they’re available, i.e. patents have expired. This recent development has saved a lot of money, because of course previously, they would just prescribe the proprietary brand they were used to. I should imagine that in any case, less money is made from patent-expired drugs.)

The point, I should think, is not primarily to persuade doctors by actually distorted medical results (but not publishing negative results, with an interested conception of ‘negative’, may be quite a problem there, a simple example of the fact that what is presented in a study does not exhaust the considerations rlevant to its evaluation), but to use the standard tools of sales and marketing to get then to prescribe in the most revenue-conducive way.

And that strategy is of course a result of the fact that the task of organising scientists to develop drugs and getting doctors to prescribe them is, for no good reason whatsoever, in the hands of a small number of organisations whose function is to extract as much profit – and board-level pay – as possible, without limit.

(And if that depressing DeLong thread is any indication of the pervasiveness of market religion, presumably this state of affairs is regarded by the ‘left’ as somewhere along a scale from ‘probably worth keeping an eye on’ to ‘the best way of doing things’.)

There are I suppose two possible problems involved: one is a reduction in the quality of medical treatments, the other inflated costs. The former is hard to quantify I’d have thought, I dunno.

But the other is an issue – Glen mentions the constant schmoozing doctors get from drug reps (I didn’t know they gave away bennies though – do they do dexys too?). I was brought up with an endless supply of pens, pads, mugs etc with drug names on them, as well as an array of executive desk toys, similarly emblazoned. This is surely intended to get name recognition/subliminal reinforcement by having the things hanging around in the surgery. Also, conferences in nice places, free meals, etc. (I’m not affected by advertising, either, but apart from present company, everyone else is.)

That’s on top of the other distorting effects of profit motive – concentrating on lucrative markets, for example by coming up with a new painkiller which can be presented as slightly better than the current default script, and thus presumably not putting as high a proportion of resources into coming up with really good new stuff. Also why has malaria not been eradicated?

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Barry 06.01.11 at 11:17 am

Glen Tomkins: “The rule of thumb is that, because of the potential for large imponderable biases inherent in observational studies, you don’t even begin to think about attributing causality until you get past 2-3:1. “

IIRC, the ‘only RR’s of 2 or more count’ was something promoted by the tobacco – well, fraudsters.

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roac 06.01.11 at 1:53 pm

why has malaria not been eradicated?

Subject to correction, I believe that in practice, the only infectious diseases subject to eradication are those that can only be transmitted from one human to another.

Malaria is embedded very deeply in an old and complex ecosystem. To wipe it out would mean killing the very last individual of all the mosquito species that transmit the parasite.

Which is not to say that we couldn’t be doing a better job of reducing its incidence. I gather that more widespread distribution of mosquito nets promises a large bang for a very small buck. I don’t know to what extent those efforts are actually panning out.

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chris 06.01.11 at 2:33 pm

Subject to correction, I believe that in practice, the only infectious diseases subject to eradication are those that can only be transmitted from one human to another.

Strictly speaking, I think you could also drive the nonhuman vector species extinct. But that’s hard to do with mosquitoes.

Hmm — it might depend on the life cycle. If a human-infecting phase is indispensable to the life cycle *and* you can get 100% herd immunity in the humans, then you might succeed in breaking the life cycle and driving the pathogen extinct without driving any of the host species extinct.

But this won’t work if other species can substitute for the humans in the pathogen’s life cycle. If the disease can promiscuously infect several species and jump from one to another in arbitrary order, you’re screwed. The other host species are always going to be a reinfection reservoir unless you drive them extinct or vaccinate every last one of *them*.

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roac 06.01.11 at 3:06 pm

Yes. I know I read somewhere, once, that it took epidemiologists about a day and a half of investigation to conclude that you could never wipe out yellow fever — because the jungles were full of monkeys, and they all had the disease in their blood. Nevertheless, yellow fever is no longer much of a threat, because there is an effective vaccine for it. But the malaria parasite, I believe, is very, very skilled at defeating the human immune system.

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Tom Womack 06.01.11 at 4:19 pm

roac: Malaria has been eradicated in a lot of places; the first great triumph of the CDC as currently shaped was the eradication of malaria in the southeastern US, and there’s a fair amount of Europe which had malarial swamps a hundred years ago and doesn’t now. And not always only because the swamps are drained. The tertian and quartern agues that you find in Pepys and Shakespeare are reasonably likely to have been malaria, and people were using quinine against it in England as early as the late 17th century.

Yes, the malaria parasite has some really nifty biochemistry for injecting itself into cells and remaining encysted within the cells and insulated from the immune system – it’s remarkably evolutionary static biochemistry, and antibodies against bits of it are one of the better hopes for a malaria vaccine.

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Glen Tomkins 06.01.11 at 5:19 pm

Barry,

The Odds Ratios from case-controls looking at cigarrettes causing lung cancer are 10-13:1, consistently across many studies in many diffeerent populations, and with a dose-response relationship where that was assessed. At that effect size, in every population looked at, with a dose-response relationship — there simply is no differential bias you can invoke to explain away the correlation as anything but causation. If you do claim some such bias, you are obligated to do a case-control or cohort that controls for it or avoids it in the study population. If you deny causation at that magnitude of OR, yes, you are like the tobacco companies, arguing dishonestly.

If you think causation is not at all proved, or even likely, at the RR of 1.3-1 level, as it was with ERT for cardioprotection, you’re not dishonest, you’re right, and likely to be proven so if an RCT is ever done.

ORs or RRs of 2-3:1 are a step above that, in that that effect size implies that there very well could be causation, that the issue needs further study, with an RCT if possible, with a cohort designed to control likely biases better than existing studies if an RCT is not feasible. Until those studies are done, caution is advisable, and it is not unreasonable to change practice to account for the possibility of causation.

I am not aware that any of the harmful effects of cigarrette use had OR/RRs that fell in that 2-3:1 range. Even if they did, we already had cigarrettes dead to rights with lung cancer causation. It’s not as if failing to prove that they also caused erectile dysfunction because you couldn’t get an OR bigger than 2:1, would mean that physicians would have to advise their patients that cigarrettes were just fine, go ahead, light ’em up.

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