GSK Announces Major Changes--Is This for Real?

Hot news coming off the NPR wires:
http://www.npr.org/blogs/health/2013/12/17/251965775/why-glaxo-wont-pay-doctors-to-sell-its-drugs-anymore
Normally I like to take a while to report on breaking news, to be sure that things are as they seem and also to gather reactions from other observers, but this is big enough to warrant immediate comment in my view.

GlaxoSmithKline has already made history within the drug industry by changing its practices in the US for paying its sales reps--no longer paying bonuses purely on volume of sales. Now the firm announces that it is changing global practices--no more paying reps on volume anywhere; no more hiring doctors as paid speakers; no more paying doctors to attend medical meetings.

In short, the company has announced that it is discontinuing many of the business practices that industry critics have held most responsible for threatening the professional integrity of medicine, and in turn making pharmaceuticals a public health threat rather than a benefit.

Why now? asked NPR. Some theories--no point launching huge marketing campaigns when there are fewer important new drugs rolling off the industry pipeline anyway; pharmascolds have been successful in getting more docs to pull back from schmoozing with sales reps and taking their bribes; the Internet is turning out to be a more effective way of getting industry-friendly information to docs without the expense of a big rep sales force; the looming Federal Sunshine Act will cause docs to think twice about accepting industry largesse in the very near future.

Are we to take this announcement at face value? It's hard, when the industry has such an extensive track record of lies, to believe that at long last, Lucy is going to hold the football and actually allow Charlie Brown to kick it. Yet folks like me have been preaching for some time now that this is what the industry should do, and that it might even be in the industry's interests to do it. So it hardly seems appropriate then to take potshots at the industry if they actually do what we've been asking. If it's real.

We need, in short, better research on what's actually changing. For example, the last big "ethics" reform of the industry took place in 2009 when the US firms voluntarily gave up handing out the pens emblazoned with drug logos and all the other "reminder" items that used to clutter physicians' offices. And what was the actual impact of those changes? I can't point to any research studies that tell us. Of course, if change occurs today, it will naturally take a while for an investigator to do the research on the consequences, and even longer for the results to then be published. So we can cautiously welcome GSK's latest statements while withholding judgment till we see the evidence.

Congratulations, Pfizer, You Are Now Officially a “Racketeering Influenced Corrupt Organization”

Thanks yet again to Dr. Roy Poses over at Health Care Renewal—
http://hcrenewal.blogspot.com/2013/12/blogscan-us-supreme-court-turns-down.html
--for picking up from some of our fellow bloggers this latest news tidbit about drug giant Pfizer.

In the past I have blogged (again thanks to Dr. Poses) about Pfizer’s rather amazing record of criminal wrongdoing:

http://brodyhooked.blogspot.com/2012/12/doing-it-again-after-pomising-not-to.html

I have also agreed that the word “corruption” is the correct term for much of what we see in today’s drug industry:

http://brodyhooked.blogspot.com/2013/09/special-journal-issue-institutional.html

And finally, I recently commented on the book by Dr. Peter Gøtzsche in which he compares the drug industry with organized crime:

http://brodyhooked.blogspot.com/2013/11/deadly-medicines-over-top-or-overdue.html

So, by way of commentary for anyone who thinks that all the above is unjustified piling on, Dr. Poses reports that the U.S. Supreme Court has refused to review a 2010 conviction of Pfizer in which the company was found guilty to violating the RICO law, and therefore was found to constitute a “racketeering influenced corrupt organization.” With the high court’s refusal to hear an appeal, the original verdict now stands for all time.

As Dr. Poses has repeated until he is blue in the face (as probably most people in New England are these days given the weather they’re having), when an organization is found guilty of RICO violations, one normally expects that some of the people who run the place are going to end up in jail. We are of course still waiting for that day to come to the drug industry. In the meantime all the big execs will presumably continue to take home their multi-million-dollar bonuses.

More on Cholesterol Guidelines: Cochrane Lets Us Down

Dr. Roy Poses over at Health Care Renewal did a nice post on the cholesterol guidelines—
http://hcrenewal.blogspot.com/2013/12/how-manipulated-clinical-evidence-could.html
--that have been the subject of my two previous posts:
http://brodyhooked.blogspot.com/2013/11/new-cholesterol-guidelines-part-two.html
http://brodyhooked.blogspot.com/2013/11/new-cholesterol-guidelinesthe-devil-in.html

The basic question, you’ll recall, is: how did we end up with supposedly “evidence-based” guidelines that read like a script written by the drug industry to sell statins, when the most accurate and dispassionate reading of the actual scientific literature arguably tells us that 1) statins are way overrated as a way to prevent heart disease and 2) that to the extent that statins do work, it’s not at all clear that they work by reducing cholesterol levels?

Well, one way this happened is that a couple of meta-analyses (which don’t do any new research but rather re-evaluate studies previously conducted) which come from supposedly neutral and respectable sources have recently set up a big cheer for statins as effective primary prevention (prevention for people who don’t yet have established cardiovascular disease). One is the CTT that we’ve already gone over in some detail, for instance:

http://brodyhooked.blogspot.com/2012/05/statins-in-water-supply-continued-why.html

The other is a recent review from the Cochrane Collaboration. This organization is supposed to be the world’s gold standard for evidence-based systematic reviews. I tell medical students that they should generally look first to Cochrane if they want reliable evidence as to how well any medical treatment works. But for all the great work Cochrane does, and their generally impeccable results, they occasionally slip up, and some reviews have been discovered in the past to have been done by people with unreported conflicts of interest.

The review of statins for cholesterol seems to be one of their flops. Dr. Poses’ post, above, provides details as to why the methods used in their review are questionable. It has also been reported that at least one Cochrane review author had financial ties to the drug industry.

This has not stopped the pro-statin crowd from running with Cochrane as their main evidence for how wonderful statins are. Last week’s JAMA featured an editorial (subscription probably required) “Accumulating Evidence for Statins in Primary Prevention,” by an author who lists about a dozen financial ties to drug-makers. The editorial and the article on which it comments both rely heavily on the Cochrane review as their evidentiary centerpiece.

Normally, when pharmaceutical marketing reaches the level of “irrational exuberance,” we can depend on Cochrane to rein in the excess enthusiasm. It is very sad to see Cochrane instead pouring gasoline on the fire.

Robinson JG. “Accumulating Evidence for Statins in Primary Prevention.” JAMA 310: 2405-6, Dec. 11, 2013.

ADDENDUM 12/20/13: I have been waiting for some backup on the cholesterol guidelines issue from people who actually have the expertise to crunch the numbers. Here's a reply by our old friend Dr. John Abramson (Overdo$ed America) to a response offered to an earlier opinion piece that he co-authored, by the authors of the Cochrane review mentioned above. The reply further develops some of the criticisms of the Cochrane review.
http://www.bmj.com/content/347/bmj.f6123/rr/678736
 

The Next Vioxx? Disease-Mongering "Low T"

Natasha Singer in the New York Times:
http://www.nytimes.com/2013/11/24/business/selling-that-new-man-feeling.html
--writes about the campaign to convince all men over the age of maybe 25 that if they ever once felt tired or run-down or in any way lacking in manly vigor, they probably have testosterone deficiency and need one of the various products to supplement their testosterone--now a $2B annual industry. It seems that the brilliance of deciding that testosterone deficiency should be called "low T" was a major breakthrough in the public acceptability of this new supposed disease state. Two executives from AbbVie, the maker of AndroGel, were named by the trade magazine Medical Marketing & Media as "the all-star large pharma marketing team of the year" for their low-T promotional campaign.

Singer makes two major points in her article--first, that Pharma has successfully skated around the FDA by pushing the idea of "low T" through unbranded promotions. If you run an ad telling the public that low T is real and serious and they should see their doctors to find out if they have it, but don't at the same time mention your drug by name, you can get away with pushing your drug for all sorts of conditions for which it has not been granted FDA approval. (The FDA, it seems, is quite old-fashioned and still thinks that testosterone replacement products should be used for medically diagnosed cases of significant hormonal deficiency.) The second point is the widespread use of questionnaires where virtually anyone will answer "yes" to at least one question, which is then supposed to suggest that you probably have low T and could benefit from treatment.

Singer mentions along the way that the risks of taking testosterone long-term when you don't have serious hormone deficiency are essentially unknown. So why does "low T" sound like the next Vioxx waiting to happen, where drug firms convince the entire world that they all need to take a drug, and only later find out the substantial increase in adverse reactions that they have now inflicted on thousands if not millions of people? (This is what a while ago Don Light and I labeled the "Inverse Benefit Law":
http://brodyhooked.blogspot.com/2011/01/inverse-benefit-law-making-sense-of-how.html).

New Cholesterol Guidelines, Part Two

When I first posted on these guidelines:
http://brodyhooked.blogspot.com/2013/11/new-cholesterol-guidelinesthe-devil-in.html
--I figured that others would soon chime in who understood the technical details much better than I did and who could therefore make clearer what the problems were.

One such contribution is now up on the Health Care Renewal blog, courtesy Dr. Roy Poses:

http://hcrenewal.blogspot.com/2013/11/confused-thinking-about-new-cholesterol.html

In a long post, Dr. Poses adds two important things to my earlier comments. First, he drills down a good deal into why the new risk calculator attached to the guidelines is flawed and premature. Second, courtesy the Pharmalot blog, he fills in more details about conflicts of interest among the guideline panelists, showing that I was too optimistic when I stated that COI was at least somewhat kept under control or at least acknowledged more. (For example, it’s nice, according to the IOM guidelines for writing good guidelines, that the chair of the panel had no financial ties to industry. But does it matter that in order to become guideline chair, he had to divest himself of a whole pile of financial ties that he previously enjoyed? Divestment: good; lots of things that needed to be divested:  perhaps not so good.)

Nevertheless, while more details are being filled in, it is still challenging to keep the big picture in view. The media accounts I’m seeing in the newspapers seem calculated to reassure patients that it only appears that the cardiology crowd is in disarray over the guidelines; actually everything is just fine, so if your doc says to take a statin, you should have full confidence that it’s good advice. In short, if the drug industry could have written the script, it would be saying what most people are now saying.

So to restore a sense of perspective, let me go back to a theme I have tried to raise on a number of occasions, for example:

http://brodyhooked.blogspot.com/2009/07/more-on-statins-new-bmj-meta-analysis.html

The old narrative, that has led to so many millions of Americans being placed on statin therapy, at great cost and at huge risk of serious side effects, is: if your bad cholesterol is high, you’re at greater risk for heart disease and stroke. Statins lower your bad cholesterol. So you need to go to the doc, get a blood test to check your cholesterol, and if it’s an eentsy bit high, start taking statins for the rest of your life.

If you carefully ask the right questions of the research that’s been done in recent years, you learn that there is a shrinking amount of evidence that supports this narrative, and a lot that says it’s in fact just plain wrong. To the extent that statins reduce your risk of future bad stuff, as they seem to, a little, in people with existing heart disease, there’s now many reasons to believe that they don’t do it by lowering cholesterol in the blood. The new guidelines, as I said in my previous post, sort-of-kind-of admit this by eliminating the need to check cholesterol levels routinely and the idea of target levels of cholesterol to shoot for.

So if the guidelines were true to the evidence, what message would emerge? The message would certainly be: the grounds on which we used to prescribe statins were all wet; there are a bunch of folks now taking statins who probably don’t need them; we need to be much more refined in selecting the smaller subsets of people who might actually benefit from taking statins.

What message is actually being disseminated? It seems to be: If you took statins under the old guidelines, have faith and keep taking them. If you were not on statins previously, don’t worry, because our new, flawed risk calculator will probably say that you too need to be on statins.

As I said, if the drug industry had been allowed to write the script for this, it would have said exactly the same thing.

Yet More on the Markingson Case at U-Minn

It has been a while since I commented on the tragic Dan Markingson case at University of Minnesota, for example:
http://brodyhooked.blogspot.com/2010/08/continuing-our-all-carl-elliott-issue.html

For some time, my colleague in bioethics, Dr. Carl Elliott, at U-Minn, was alone in pressing for a full investigation of this case that led to a young man committing suicide while enrolled in a university-conducted, industry-sponsored clinical trial of psychiatric drugs, when his mental state would have appeared to preclude the possibility of his giving proper informed consent to participate in the trial. More recently, however, as a recent piece in Minnpost summarizes:
http://www.minnpost.com/second-opinion/2013/11/u-m-bioethicist-latest-call-independent-look-schools-troubling-markingson-cas
--Dr. Elliott has been joined by his U-Minn colleague in bioethics, Dr. Leigh Turner, and also by Dr. Trudo Lemmons at the University of Toronto, in approaching the University administration and demanding a thorough investigation and accounting. (Full disclosure: I am a signatory to the petition that Dr. Lemmons circulated.)

You might wonder why I continue to call attention to this case, which the University insists is old news, was previously investigated and they were found blameless, and these are just malcontents trying to stir up trouble. Besides all the important ethical issues about the ethical conduct of research and informed consent and protection for psychiatric patients, there is what happens when a University decides to get into bed with Pharma and accept big research grants--and then to decide that the faculty who attract those grants, by doing Pharma's bidding, are their best faculty and should be properly rewarded for the largesse they are bringing in. There is further the question of what happens when something ethically questionable is alleged in one of these studies; and whether the University will then remember that it is supposed to be about good science and about the public interest, or whether the instinct of self-preservation takes over and the response is stonewalling and obfuscation.

Dr. Turner in the Minnpost interview is commendably noncommittal over whether any actual wrongdoing occurred, and in calling solely for more information to be disclosed. I would say that enough is known so far to show that Drs. Elliott, Turner, and Lemmons are fully justified in demanding more answers and in saying that the so-called investigations that have taken place so far are woefully inadequate. People who really care about the reputation of the University of Minnesota would be listening to them rather than continuing to attack them.

Generic Prescribing and Conflicts of Interest

The great investigative reporting team at ProPublica did a good job on money wasted in Medicare through failing to prescribe generic drugs:
http://www.propublica.org/article/medicare-wastes-billions-on-name-brand-drugs

Now, the price of drugs, and generic prescribing, is not a hot topic on this blog, so the main thing I wanted to point out is one fact from the article. The authors note that a relatively small number of Medicare prescribers are responsible for a hugely disproportionate excess of brand-name prescriptions and hence unnecessarily high costs. They then  proceeded to check out their Dollars for Docs tool and noted that these same docs also seemed disproportionately represented among those receiving payments from drug companies. When ProPublica reporters visited some of the offices of these docs, they could hardly get in the door for all the drug reps waiting in line to handout free samples and other goodies.

As was nicely summarized in the excellent review article by Spurling and company from Healthy Skepticism:
http://brodyhooked.blogspot.com/2010/10/major-new-study-published-in-plos.html
--all the available evidence shows that taking money and information from the drug companies is associated with irrational prescribing and more expensive prescribing. I can think of few things more irrational than routinely prescribing brand-name drugs when a generic equivalent is available; and that certainly leads to higher costs.