On the European Front: Yet More Industry Corruption

I've so far restricted my periodic reports of settlements and guilty verdicts against the big drug companies to US-based actions. Dr. Roy Poses over at Health Care Renewal--
http://hcrenewal.blogspot.com/2013/12/the-camels-aching-back-johnson-and.html
--being a more cosmopolitan sort of guy, picked up this news item, which he says got very little play in the US media.

Johnson & Johnson got hit with a more-than 10-million euro judgment and Sandoz with a 5 million euro judgment for anti-competitive activities around the fentanyl opiate-pain-killer patch. The patch was about to go off patent and Sandoz was poised to offer a generic equivalent, but instead, the two companies entered into a so-called cooperation agreement, which meant that J&J paid off Sandoz to delay their generic so that prices could stay high on the brand-name patch. This is a form of "evergreening" that we've seen frequently in the US, and apparently the Europeans don't like it any better than we ought to.

OK, so as we have seen in the past, a few million dollars is chickenfeed to these big firms. Dr. Poses goes into some detail on his blog about the former CEO of J&J, on whose watch this breach occurred along with numerous other illegalities, and how he retired with huge bonuses and a ton of J&J stock; and how the current CEO is already pulling down a big paycheck with no indication that any changes are occurring in how the company is managed. So far, same ol' same ol'--we have covered many times, as did Dr. Poses even more times, how no actual individual ever seems to be to blame for these misdeeds, and somehow the misdeeds just keep happening as a result.

But for our edification, Dr. Poses adds a bit of a new twist by reminding us of a partial rundown of the J&J board of directors:

• Dr.Mary Sue Coleman, the president of the University of Michigan
• Dr. Michael M.E. Johns, Chancellor of Health Affairs Emeritus at Emory University
• Dr. A. Eugene Washington, Dean of the medical school and Vice Chancellor of Health Sciences, UCLA 
• Dr. Susan Lindquist, Professor of Biology at MIT, former director, Whitehead Institute for Biomedical Research
• Dr. Mark McClellan, former head of both FDA and Center for Medicare and Medicaid Services, senior fellow, Brookings Institution

Dr. Poses suggests that even if the various corporate types on the rest of the board don't give a hoot about integrity or the well-being of patients, these people are supposed to have a set of values that takes such things seriously. But presumably the wrongdoers in high executive positions at J&J could not keep committing their sins, and then being richly rewarded for them, unless all these board members acquiesced in the practices. Which, in turn, suggests that the leaders of health care and of academic research cannot be distinguished from corporate execs these days. All these folks appear simply to take it for granted that once you rise to a certain level of power in the system, it's okay to extract all the money you can, no matter what the impact on public health or well-being.

What’s in the “Free” Sample Closet? Very Little of Value

I’ve blogged about the issue of sample drugs in doctors’ offices mostly in the earlier years of this blog, except for one post this past spring:
http://brodyhooked.blogspot.com/2013/05/recently-i-posted-on-report-suggesting.html

Now we can add a study published a while ago by a medical student, Kari Evans, from University of Arizona, and Drs. Steven Brown and Gerald Smetana:

http://www.jabfm.org/content/26/4/380.long

 The folks (I’m guessing they sent the student) snooped into 10 sample closets of primary care offices in Phoenix and made a list of 23 different medications that they found in 7 or more of the closets. They then asked: Is this medicine novel? Is this medicine useful? They had formal criteria for judging each of these variables. They found that 22 of the 23 had a cheaper generic medication available for the same condition, and that only 3 medicines had scientific evidence of superior patient outcomes.

In short, had the docs not had these samples to give out to patients, it’s hard to imagine that the patients would have been any worse off, or that the docs would have missed a chance to become informed about an important breakthrough in medical science.

The study also nicely illustrated why companies give out “free” samples. The mean cost of a month’s supply of the 23 drugs was $178, with the highest-cost drug ringing up a bill of $749. If a patient can be hooked on these meds with free samples, and then the prescription is continued later on, you see how much the company stands to gain—especially knowing that almost all the meds have cheaper generic alternatives.

 
Just a bit more evidence as to why the sample closet ought to go—and if you’re interested in the issue in any depth, the article provides an excellent review of the previous literature.

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.

New Cholesterol Guidelines—The Devil in the Details

I had been holding off on commenting on the cholesterol treatment guidelines recently issued by the American Heart Association and the American College of Cardiology:
http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a
--because I know that many of the friends that I have previously quoted here, the thoughtful naysayers in the put-everybody-on-statins campaign, were sharpening their statistical knives to go after the new document, and I hoped to be able to link to a truly scholarly dissection of the issue.

I am perhaps jumping the gun a bit egged on by today’s All Things Considered on NPR, which had a lead story on the critics of the risk calculator that’s part of the guidelines, a debate that apparently blew up at the Heart Association’s big annual meeting. So with apologies for my own inability to drill down with any statistical acumen, I will offer a preliminary read.

If you just looked at the guidelines quickly, you’d say that the guideline writers had had a sudden attack of brilliance. Some of the basic points that this blog has been carping on for several years now are reflected in the document:

• Treatment with statins should be based on the patient’s heart-disease-stroke risk level and not on a blood level of cholesterol.
• There’s no evidence that shooting for any specific target level of cholesterol is better than simply placing the patient on a reasonable dose of a statin and keeping them there.

Not only that, but the guideline panel seems actually to have taken on board some of the criticisms of conflicts of interest. The chair of the panel reports no conflicts, and while a few of the panelists have seriously long lists of industry funding, many do not. And there’s quite detailed disclosure. (I admit that I did not check to see if any of the people reporting no COI actually could be found to be on the industry payroll.)

So—what’s not to like? Well, a number of things. What the panel giveth, they then taketh away, usually in the fine print of the document.

The panel realizes that there’s no good evidence to recommend a particular target level of cholesterol. But they are impressed (as we’ll see) with the studies that show that lower LDL cholesterol is associated with lower risk. They then urge the physician to prescribe a “moderate” or a “high” intensity dose of their favorite statin, with the idea that the end result will be a certain percentage drop in the LDL level—with the additional proviso that if you don’t achieve that level of drop, you will need to up the dose. So the idea of treating to a target level went out the front door and snuck back in the rear window.

Where did this panel get the idea that you need to reduce LDL by a certain percentage? Well, it turns out that they were quite enamored of one particular study, the CTT meta-analysis in Lancet in 2012. I tried to explain at some length:

http://brodyhooked.blogspot.com/2012/05/statins-in-water-supply-continued-why.html
--why that study was deeply flawed because it answered the wrong question. Moreover, that was not an independent clinical trial; it was a re-analysis of data from many previous trials, and when analyzed by people who are not on the statin bandwagon, all those previous trials yielded much less optimistic results in favor of prescribing statins. Yet if you look at the evidence table that the current panel relies on, “CTT” jumps off the page at every turn.

Next we come to the point that NPR addressed today—the risk calculator. If you no longer treat with statins based on level of blood LDL, but based on the patient’s level of risk, then it becomes critical that you have a reliable measure of that risk. The critics are shouting today that the calculator that the panel favors way overestimates heart-disease risk. Before I get into that discussion I will wait to see one figure that I think is critical—how many additional people will be prescribed statins in the US based on this risk calculator? There are no doubt some people that could benefit from statins who are not now getting them. But there are a whole bunch more IMHO who are currently on statins because their blood tests looked bad and yet they have no diagnosed heart disease and are at reasonably low risk. So if the calculator leads to a net increase in statin prescribing, we know it has to be a move in the wrong direction.

But wait, as those TV ads say, there’s more. Two things are almost completely absent from these guidelines, that ought to be front and center in any practical approach to evidence-based prescribing of statins today. First is the concept of NNT. I didn’t see anywhere where the guidelines stated an actual NNT. The assumption is that if a study shows that statins offer any benefit for any particular group, then you should prescribe the statin—never mind if you have to give a statin to 400 people to prevent 1 cardiovascular event. (If you had an NNT, then you could talk further about shared decision making, giving the patient the facts and letting them decide if they wanted a statin—another concept curiously lacking from these guidelines.) Finally, what’s massively missing is any significant discussion of the downside of statins. According to these guidelines, a vanishingly small number of patients have any serious side effects. The possibility, for example, that as many as half of all patients on statins have some muscle aches or weakness, or the emerging worry that dementia may be more common in statin users, gets no mention whatsoever.

Bottom line—it looks worrisomely like what I concluded with CTT—even if these guidelines were not written by people in the pay of the drug industry, they could just as well have been. And somehow, while important new evidence against the routine use of statins, and suggesting that we really don’t know much about the true mechanism by which these drugs work in the cases where they do, crept into the guidelines for the first time, the bottom line is largely unaffected by such enlightened thoughts. We’re back to putting statins in the water supply.

NOTE ADDED 11/20: I can now cite a comment by some real experts, Drs. John Abramson and Rita Redberg, in the New York Times:
http://www.nytimes.com/2013/11/14/opinion/dont-give-more-patients-statins.html?_r=0
These two estimate that the new guidelines would increase the number of people considered candidates for statin therapy by 70 percent, with 18 percent of these at risk for the adverse effects of statins, with no evidence of fewer deaths from heart disease or stroke as a result. (They mention what most statin advocates ignore, that even the most successful clinical trials tend to show that statins reduce the risk of heart attack or stroke, but still have no impact on overall mortality.)

Welcome to the Harm/Hope Ratio: An Alternative to Industry Brainwashing

I have been mulling over several new posts, including one on the recently issued cholesterol treatment guidelines, and have come to the realization that underlying all of the messages I most want to convey is one basic point.

In keeping with the recent post:
http://brodyhooked.blogspot.com/2013/10/an-epidemic-out-of-control-poor.html
--I have become increasingly impressed with the overall epidemiological picture painted by recent data on the harm caused by prescription drugs. We have reviewed Donald Light's data:
http://brodyhooked.blogspot.com/2010/08/how-many-new-drugs-are-lemons-ask.html
--showing that people taking their drugs as prescribed (not errors; not overdoses) is currently the 4th leading cause of death in the U.S. Just to up the ante a bit, we more recently encountered Peter Gøtzsche's statement that this should be elevated to the 3rd leading cause of death:
http://brodyhooked.blogspot.com/2013/11/deadly-medicines-over-top-or-overdue.html

So the worrisome bottom line is that all this time, as we have been sold a bill of goods from the drug industry about how if we do one single thing to get in the way of their excessive profiteering, we'll suffer a screeching halt to medical progress, we have ignored the fact that the real "progress" in recent years is how many prescription drugs the average American is already taking and the harm done to them in terms of both mortality and morbidity from this over-drugging.

My friends in the evidence-based medicine movement have tried to chip away at this industry brainwashing particularly by attacking the commonly heard phrase "risk-benefit ratio." They point out quite reasonably that this term, which seems totally objective on the surface, actually hides a serious bias. We talk about "benefits" as if they were assured (no "risk" of benefit) but we only allude to harm as something that might or might not happen. The EBM gurus now say that we should always be precise and talk about the "harm-benefit ratio," unless we want to get really wordy and talk about the "probability of harm-probability of benefit ratio."

This leads me to one of my periodic modest proposals. I suggest, in light of the recent epidemiologic evidence, that we should now begin to talk about the "harm-hope ratio." I propose this term because:

• As above we have solid epidemiologic evidence that the American public is killing ourselves by ingesting way too many prescription drugs.
• When we do the usual studies, we are generally shocked by the high number-needed-to-treat (NNT) attached to commonly used drugs. The really great drugs like metformin for Type 2 diabetes usually run an NNT of around 10-30--that is, 10 to 30 patients have to take the drug for a certain length of time to achieve the hoped-for therapeutic benefit. The crappy drugs like statins for primary prevention of heart disease run NNT's typically in the several hundreds.
• Therefore, the usual situation when we take prescription drugs--we can be almost certain that at least on the population level, harm is being caused; and we accept the harm given our hope that we might be the lucky soul who's the 1 out of 30, or the 1 out of 400, who will actually derive some significant therapeutic benefit, like not dying of a heart attack in the next few years.

Maybe if we were more honest and started talking widely about the harm-hope ratio, instead of the highly misleading risk-benefit ratio, we'd start to turn the proverbial ocean liner around.

J&J's Recent Settlement: For the Record

Once again, nothing new here for regular readers; but just to be sure that we are keeping up to date for the record, we should note yet another huge (more than $1B) legal settlement involving a major drug firm. A comprehensive account can be found over at our friends, Health Care Renewal:
http://hcrenewal.blogspot.com/2013/11/another-and-huge-22-billion-settlement.html

Let's return to our standard form for such matters:
Company: Johnson & Johnson
Drugs involved: Risperdal, Natrecor, Invega
Allegations: Off label marketing, kickbacks
Amount of settlement: $2.2B
Settlement equals what percent of annual drug sales: Approximately 87% as best as I can estimate for all 3 drugs, making this one of the heftier settlements on record
Did company admit guilt? Supposedly J&J admitted "accountability" but not wrongdoing, whatever that means

In what appears now to be the formulaic response to any such settlement, J&J spokespeople deny that the company is guilty of any wrongdoing, but say that the settlement was paid simply so that the company can move on and put this unpleasantness behind them. I can sort of understand this; if you paid me $2.2B, I can imagine a good deal of moving on that I would be able to accomplish, and I would certainly put a lot of unpleasantness behind me.

Dr. Roy Poses, as usual, noted that magically, J&J managed to do this bad stuff without any individual human being doing anything wrong and requiring punishment, and opines that until individuals start doing jail time, we should not expect any changes in industry behavior. For a confirming opinion, recall our recent post:
http://brodyhooked.blogspot.com/2013/11/deadly-medicines-over-top-or-overdue.html
--and the quote therein: “I dedicate this book to the many honest people working in the drug industry who are equally appalled as I am about the repetitive criminal actions of their superiors and their harmful consequences for the patients and our national economies. Some of these insiders have told me they would wish their top bosses were sent to jail, as the threat of this is the only thing that might deter them from continuing committing crimes.”

Catching Up: Recent Articles of Interest

Once again I'm indebted to my friends Rick Bukata and Jerry Hoffman at Primary Care Medical Abstracts for pointing out papers that I missed when first published in the last 6 months or so (subscriptions may be required to access articles).

First off is a review by authors from London, Australia, and Stanford U. (the latter being our old pal John Ioannidis). Nothing really new here for regular readers of this blog, but the article is a nice update on the most compelling recent evidence for the various ways that undue industry influence distorts medicine. Those wanting to be sure to cite the most recent and comprehensive evidence will want to have this handy.

Next is a study out of UCSF, co-authored by Lisa Bero, another name familiar to our regular readers. At question here is what conflict-of-interest guidelines govern the activities of the 51 state Medicaid boards that decide what drugs should be covered by these tax-supported plans for low-income patients. The authors were able at first to get only 14 of these guidelines off websites or other easily available sources, and by further correspondence and begging and pleading they eventually got a total of 27 guidelines. Only 4 of the 27 guidelines seemed really strict on banning COI with industry, and in many cases they were told that the guidelines are not for public disclosure. Excuse me? A taxpayer-supported public program, and the guidelines to govern COI are secret??? What the heck is going on here? The overall situation is obviously highly unsatisfactory.

Stamatakis E, Weiler R, Ioannidis JPA. "Undue Industry Influences that Distort Healthcare Research, Strategy, Expenditure and Practice: a Review." European Journal of Clinical Investigation 43:469-475, 2013.

Nguyen NY, Bero L. "Medicaid Drug Selection Committees and Inadequate Management of Conflicts of Interest." JAMA Internal Medicine 173:338-343, March 25, 2013.

Trial Registries, Again--Non-publication of Large Trials

I have blogged in the past--
http://brodyhooked.blogspot.com/2010/06/more-on-trial-registries-any-impact-on.html
--about the hope that mandatory registration of clinical trials would end some of the lack of transparency that currently surrounds industry-sponsored drug studies. In general, the previous studies indicated a lot of problems despite the registry, including frequent changes in study end-points, for example.

The BMJ recently published a new study:
http://www.bmj.com/content/347/bmj.f6104
--by a group primarily based at University of North Carolina, that looked only at one outcome--how likely was a trial that included at least 500 subjects to publish results within about 4 years of completion? Note that they did not look at whether anyone juggled the trial design or methods, just whether any results at all were published in peer-reviewed journals or on the registry website itself. The authors chose only large studies because they judged that common excuses for non-publication--we got too busy; or we submitted and the editors rejected the manuscript--would be much less likely to hold for trials of this size.

Basically the authors found that 29% of these large trials remained unpublished. Of that 29%, an additional 22% had some results available through the trial registry itself. The authors commented that this latter is not an optimal result, as the journal peer review process is presumably valuable for identifying possible flaws and gaps in study methods. Industry-sponsored studies were more likely than others not to be published (32% vs. 18%). Put another way, industry-sponsored trials accounted for 88% of all the unpublished trials.

The present authors highlight an ethical concern that I mentioned in HOOKED. When people volunteer as subjects in a research trial, they believe that they are doing something in the service of science. If the results of the trial are never published, their "contract" with the investigator is thereby violated. Hence investigators have an ethical duty to do their best to publish research results, quite apart from whatever other obligations they may also be under.

This study, as noted, merely looked at whether any results were published in peer-reviewed journals; they did not ask whether the methods reported in the final paper matched what had been entered into the registry. So we still could have had, among the trials that were published, cases of industry-sponsored trials changing the endpoints or otherwise adding unscientific spin to make the company's drug look better, as noted in previous research. In short, the present study probably underreports by a considerable extent the continuing problems with the commercial control over pharmaceutical research. Even so, it highlights the fact that merely creating a mandatory trials registry has been far from solving the basic problem.

Pharma Issues at the American Society for Bioethics and Humanities Annual Meeting

I began writing this post from Atlanta where I was (as usual this time of year) attending the annual meeting of the American Society for Bioethics and Humanities. In past years there has been maybe one session per year on something directly related to Pharma issues, so I was impressed to see at least three sessions on this year’s program. Here I report on a panel, “Bioethics Capacity Building in a Corporate Setting: One Pharmaceutical Company’s Experience,” presented by two folks from Eli Lilly and two distinguished academic bioethicists who have served for 15 years on the company’s bioethics advisory panel. The panel moderator was Luann E. Van Campen, PhD, head of the Bioethics Program at Lilly, and one of the panelists was Donald G. Therasse, MD, VP for Global Patient Safety and Bioethics at the firm, to whom Dr. Van Campen reports.

I gather from the presentation that Lilly has had an advisory committee on bioethics for 15 years, but that the internal bioethics program was inaugurated in 2008. You can find out more at: http://www.lilly.com/research-development/approach/research-ethics/Pages/bioethics.aspx

The two academic bioethicists on the panel were indeed heavy hitters—Tom Beauchamp, PhD of the Kennedy Institute of Ethics at Georgetown, co-author of what most regard as the canonical textbook in the field, Principles of Biomedical Ethics; and Robert Levine, MD, of Yale.  I’ll focus mostly on what Dr. Beauchamp said as Dr. Levine indicated he endorsed almost all the former’s comments.

The academics reminded us that the bioethics advisory board at Lilly has so far concentrated its work in only one area—the ethics of research on human subjects. (The case study Dr. Levine discussed had to do with clinical trials in a poor country of a drug that might then be unaffordable to the population of that country.) Organizational or business ethics related to Lilly as a corporation was simply not on the agenda. Therefore, the academics said, apparently with justification, that they saw very little difference between being a paid consultant for Lilly and consulting on any bioethics body within their own university or in the academic world.

In response to an audience question, Dr. Therasse made an interesting comment. He said that perhaps in a few years, the bioethics program at Lilly would branch out and start to address these wider ethical issues. However, Lilly right now, like many of the large drug firms, is under a corporate integrity agreement with the U.S. Department of Justice. Until that agreement expires, the staff people who might work on that wider ethical inquiry have their hands completely full doing all the required compliance tasks with the corporate integrity. When the agreement expires, those people will presumably be freed up.

Dr. Therasse did not tell the audience what the corporate integrity agreement was triggered by, so I can’t be sure that it relates to this previous post:

http://brodyhooked.blogspot.com/2009/01/lilly-fine-for-zyprexa-off-label.html
But consider what’s apparently being said. Lilly was forced by a legal settlement to improve its corporate ethics behavior. They now say that they don’t have enough staff to attend to a full bioethical inquiry into their company’s activities because they are too busy complying with that settlement. But as soon as the settlement ends, then they can take the time and trouble to think more about ethics. Everybody got that? (I’m pretty sure that Lilly monitors this blog, so if I’ve been unfair to you guys, tell me, OK?)

My main concern, however, was not with Lilly but with my academic bioethics colleagues. Dr. Beauchamp began his talk by noting that some in our field criticize him for consorting with industry in this fashion. He then characterized their criticism using a series of straw-man arguments, such as they thought it was bad to make profits. He failed to address a single substantive argument made against close relations with Pharma based on actual patterns of industry behavior. So far as Beauchamp was concerned, there simply was all upside and no downside to consulting with drug firms. We recently reviewed the new book by Peter Gøtzsche that was highly critical of the industry:

http://brodyhooked.blogspot.com/2013/11/deadly-medicines-over-top-or-overdue.html
If you were to listen to Dr. Beauchamp’s talk, you’d have no idea that such a book ever could have been written.

What was embarrassing about this presentation was that if a physician/scientist had given such a talk, explaining why he was a paid consultant to Eli Lilly, anyone with any familiarity with the industry would have labeled the talk as the typical rationalization that people with their hands in the till give when in denial of their actual conflict of interest. Here we have one of the bright lights of the field of bioethics imagining that he is giving a presentation that defends his role as a paid industry consultant, apparently not even realizing that he is merely giving that much more ammunition to critics of current financial entanglements.

To elaborate further on a theme that I have stressed repeatedly here, I want to contrast the positions of my academic colleagues with that of Dr. Van Campen. I may agree or I may disagree with her ethical thinking on a variety of issues, but at least we know fully where her loyalties lie. She’s a paid Lilly employee, and we must imagine that the minute that her activities were judged by Lilly to be bad for business, she’d be out the door. My concern rather is for people like me who imagine that we are independent, objective scholars, but that we can accept a role as a paid consultant to Lilly or any similar company while still adhering with full integrity to our independent stance. This panel, if anything, further demonstrated the fallacy of that view.

Deadly Medicines: Over the Top or Overdue Wake-up Call?

I promised a while back:
http://brodyhooked.blogspot.com/2013/10/corporate-drug-pushers-and-their-blame.html
--to provide a book review of the new volume by Peter C. Gøtzsche, Deadly Medicines and Organized Crime: How Big Pharma Has Corrupted Healthcare (New York: Radcliffe Publishing, 2013).

The book features Forewords by two heavy hitters, Richard Smith, former editor of BMJ, and Drummond Rennie, long-time deputy editor of JAMA. If you read between the lines, the two editors both convey more or less the same message—this guy comes across as a raving lunatic, but it would be a shame if you were put off by that tone, because he actually has something important to say.

By way of the lunacy quotient, I append a representative list of quotes:

• “In the United States and Europe, drugs are the third leading cause of death after heart disease and cancer.”(1)
• “The main reason we take so many drugs is that drug companies don’t sell drugs, they sell lies about drugs. Blatant lies that—in all the cases I have studied—have continued after the statements were proven wrong.”(2)
• “The book addresses a general system failure caused by widespread crime, corruption and impotent drug regulation in need of radical reforms. Some readers will find my book one-sided and polemic, but there is little point in describing what goes well in a system that is out of control. If a criminologist undertakes a study of muggers, no one expects a ‘balanced’ account mentioning that many muggers are good family men.”(2)
• “I dedicate this book to the many honest people working in the drug industry who are equally appalled as I am about the repetitive criminal actions of their superiors and their harmful consequences for the patients and our national economies. Some of these insiders have told me they would wish their top bosses were sent to jail, as the threat of this is the only thing that might deter them from continuing committing crimes.”(3)
• “[Industry] clinical trials are rarely research in the true sense of the word…it is marketing disguised as research. The trials are often flawed by design, additional flaws are introduced during data analysis, and the misleading results are spun to make sure that whatever an honest trial might have shown, the trial concludes something that is useful for boosting sales.”(87)
• “We should ask our politicians to forbid marketing of drugs, as it is harmful, just like marketing of tobacco is, which is why we have prohibited tobacco advertisements…. There is no need for drug marketing, as the products should speak for themselves.”(94, 275)
• “Anyone of us will need to consider the pros and cons of taking a drug, and our doctor isn’t always the best person to ask, as most doctors have been brainwashed and many have been bribed by the drug industry.”(129)
• “We cannot trust industry trials at all and the reason is simple. We don’t trust a person who has lied to us repeatedly, even though that person may tell the truth sometimes.”(265)

Throughout the book, Gøtzsche uses the organized crime motif to characterize the drug industry. This is quite deliberate and measured. He argues that something counts as organized crime when:

• They kill people
• They lie about what they do
• They routinely break the law as a part of their business practices
• They use their ill-gotten gains to corrupt the government regulatory apparatus so as to be allowed to continue to operate

Gøtzsche is a physician, epidemiologist and research methodologist, and has achieved prominence as head of the Nordic Cochrane Center, a part of the Cochrane Collaboration which is generally recognized as the most reliable and independent assessor of medical data—a sort of gold standard if you want to know: how good is the evidence that any treatment works for any disease? So this guy is not one to fly off the handle and make charges that he cannot document with solid evidence. (I give him some credit for solid evidence since he several times cites HOOKED.)  I have not always agreed with Gøtzsche in the past—he’s co-author of a widely cited meta-analysis in the New England Journal (2001) purporting to show that the placebo effect, one of my own pet research interests, probably doesn’t exist. But while some of the evidence he brings forward in this volume is new to me, and much is worth reading simply to get the European perspective on the issue, very little of what he says would be of any real surprise to anyone who has read HOOKED and/or kept up with this blog.

In a minor way, the evolution of this blog parallels what Gøtzsche is up to. If you take the trouble to go back and look (I don’t advise it), check out how long it took me to use the actual words bribery and corruption in describing Pharma behavior. I now use those words unabashedly because I am quite secure in knowing that the behavior is accurately described by such terms, and there is no point in pussyfooting around the real and serious problem the behavior poses. If we get overly obsessive about not appearing intemperate, we pay the price of failing to endorse the really basic and drastic reforms that are needed to clean up the current mess.

An Epidemic Out of Control: Poor Children and Psychiatric Drugs

An excellent, but in its own way truly horrifying presentation was given at the recent annual meeting of the American Society for Bioethics and Humanities in Atlanta by Dr. Melody J. Slashinski of the Center for Medical Ethics and Health Policy at Baylor College of Medicine up the road in Houston. Her account of some of the fallout from intensive marketing of psychotropic drugs suggests a serious public health threat to the well-being of children.

Dr. Slashinski presented the findings of a participant-observer study of African-American single moms trying to raise their kids in a public housing project in Houston. The material she reported was impressive in showing the extent to which she gained the trust of this community and got her informants to reveal things they would normally keep hidden from outsiders. In response to a question about this Dr. Slashinski said that the nickname given to her among this community was “the keeper of secrets.”

Dr. Slashinski reported an effective folk-knowledge network that linked these mothers and that conveyed information about the dangerous side effects of drugs commonly prescribed for kids today for ADHD, bipolar disorder, etc. I doubt these mothers had read Robert Whitaker’s Anatomy of an Epidemic:

http://brodyhooked.blogspot.com/2010/05/whitakers-anatomy-of-epidemic.html
--but they might well have for the accuracy and incisiveness of what they seemed to be aware of. The net result was that many felt they had a critical obligation as good mothers—save their children at all costs from these medications.

That might sound easy to do, but the data went on to show that it’s extremely difficult in this population especially. The mothers also feared, quite realistically, that any evidence of “medical noncompliance” on their part would end up with a report to Protective Services and eventually losing custody of their children. So the stories Dr. Slashinski told generally depicted a delicate balancing act—moms on the one hand certain that they would not give these medicines to their children, and on the other hand going through as many hoops as they could to appear compliant and submissive to the medical system so as not to set off alarms.

There was another group of mothers who were intent on protecting their children—but they elected to do so by giving the medications despite their fear of side effects. This strategy was based on a sort of pact with the devil—if they gave the children meds then the outer world might be compassionate and regard their children as sick, whereas if they withheld the medications, the world was almost sure to regard their children as bad. Being seen as bad was viewed by these moms as much more dangerous for the kids than being sick.

The other reason saving your kids from the harms of these drugs is difficult was illustrated by an account Dr. Slashinski gave of one pediatrician office check-up visit with a mom, a 9-year-old son, and 8-year-old daughter that she personally witnessed. The son had already been diagnosed with ADHD and the mom had not admitted to the pediatrician that she was not giving the son his meds (even though overall the mother liked and trusted this pediatrician a lot). As the doctor entered the exam room, she wheeled in a cart laden with equipment such as tongue depressors, and the son immediately went to the cart and started rummaging through it. The doctor used this as a launch for a lecture to the mom on how the son clearly had serious ADHD and really needed his medications.

The doctor then examined the daughter and said something at one point about her “boobies.” The daughter apparently became offended by this comment and stopped cooperating with the exam. The doctor immediately asked the mother how often the daughter had these “tantrums” and started talking about the possibility of bipolar disorder. The visit ended with a psychiatric referral to evaluate the daughter and a new prescription for the ADHD medication for the son. The mom told Dr. Slashinski that she would continue to withhold the son’s medicine, but felt she needed to take the daughter to see the psychiatrist for fear of the consequences of being “noncompliant” if she didn’t.

OK, that’s the data presented by Dr. Slashinski; here’s my comment. Whitaker and others have demonstrated that the sheer number of kids now being prescribed medicines for ADHD, bipolar disorder, and other psychiatric diagnoses is so massive that there can be no biological explanation for how such a huge percentage of the pediatric population of the U.S. suddenly became crazy. The only possible scientific explanation for this phenomenon is overdiagnosis and consequent overuse of medicines whose long-term safety in kids has never been shown, and whose short- and long-term adverse consequences are legion. It is not only psychiatrists but my fellow primary care physicians (as shown by the pediatrician in the case study) who have bought into this insane model of diagnosis and treatment—not the least because of how quick it is to slap on a diagnosis and write a prescription, and how hard (indeed, in cases like this, nearly impossible) to fully inquire into the child’s psychological and social environment and then identify helping interventions if needed. Are things truly so bad that the only way parents can protect their kids is by not taking them to the doctor?

Everything I just said applies to the American society at large. But now, back to Dr. Slashinski’s data, we see that when American society gets the sniffles, poor minority populations come down with pneumonia. It appears to be the new social campaign to get all kids to be as passive and submissive as possible, no matter how much we have to drug them. But this is especially true of black kids, especially black males, who as shown by the Trayvon Martin case can be thought to pose a threat to the lives and safety of the white community merely by existing—let alone by acting curious and assertive. So the call goes out even more shrilly to diagnose this group of children and medicate them, and the parents have even less social authority and credibility to question this.

In short, the epidemic of psychiatric overdiagnosis and overtreatment that Whitaker identified is truly out of control, if Dr. Slashinksi’s findings are in any way representative. And the medical and medical-scientific community bears major responsibility for this state of affairs.

Controlling the Channels: The VA and Diabetes

A study and a commentary (subscription required) from last November illustrate a phenomenon we have previously discussed called “controlling the channels”:
http://brodyhooked.blogspot.com/2010/06/how-does-drug-industry-exert-power.html
--as it applies specifically to diabetes:
http://brodyhooked.blogspot.com/2011/08/controlling-channels-pushing-pharma.html
http://brodyhooked.blogspot.com/2012/04/yet-more-on-broken-disease-model-of.html

A group from the Pittsburgh VA looked at variability across their system’s outpatient facilities in prescribing two expensive drugs for Type 2 diabetes—the glitazone-type drugs, and long-acting insulin analogues. They selected these categories because a) the best evidence shows no advantage for the vast majority of patients compared to much cheaper drugs; and b) the VA’s own formulary discourages their use.

The authors found that despite the evidence and VA policy, nearly 9 percent of the patients received a glitazone, with an incredibly wide range of 1.5-26 percent among facilities. Of those taking some sort of insulin, about 40 percent were getting the high-priced versions, with again a very wide range of 4 to 71 percent. (If we looked at non-VA practices, these percentages would no doubt be higher.)

Drs. Timothy J. Wilt and Amir Qaseem, also of the VA, commented on the study and speculated on why these results. It is notable that one factor that would normally have loomed large in data from standard community practice was not mentioned here as a possibility—enthusiastic drug marketing—since the VA, among all healthcare settings in the US, may be the most insulated against drug detailing. However, a factor that was identified was specialty guidelines and pay-for-performance criteria that reward trying to reduce the patient’s blood sugar to the lowest possible levels, regardless of what harm that might cause the patient, and regardless of the evidence that reducing sugar does not prevent major diabetic complications.

This in turn drives home the point about “controlling the channels”—that the way drugs are marketed in the US, the people who write the clinical practice guidelines and the pay-for-performance rules end up being brainwashed by the industry “line” on diabetes. This means that even physicians who are safely kept in a cocoon and protected from the wiles of detail people may still end up practicing in a way that’s heavily influenced by Pharma-think. We can run but we can’t hide.

Wilt and Qaseem have what seems a good idea about guidelines and pay-for-performance—it’s not enough to promulgate guidelines that only talk about ideal treatment. When in a case like diabetes, overuse of various drugs has been identified as a specific problem, guideline writers ought to pick criteria for overuse and specifically identify, and penalize, physicians who meet those criteria.

Gellad W, Mor M, Zhao X, et al. Variation in the use of high-cost diabetes mellitus medications in the VA healthcare system. Archives of Internal Medicine 172:1608-9, Nov. 12, 2012.

Wilt TJ, Qaseem A. Implementing high-value, cost-conscious diabetes mellitus care through the use of low-cost medications and less-intensive glycemic control target. Archives of Internal Medicine 172:1610-11, Nov. 12, 2012.

Drug Money Down Under

I was recently alerted to a series that The Global Mail in Australia has been running during this past year:
http://www.theglobalmail.org/features/in/drug-money/

The various stories recount how the industry spends its money wining and dining physicians, paying consulting fees to prominent specialists, and lobbying aggressively. No real surprises for those of us who've been following the story all along, but a chance to see what specific issues arise in Australia--and discouraging to learn that some experts there who think things are totally out of control look to the US as a model of much better regulation of industry-professional relationships.

One story that seems particularly worrisome is:
http://www.theglobalmail.org/feature/medical-ethics-under-the-knife/707/

Presumably the Royal Australasian College of Physicians has long had an exemplary ethics committee and democratic review process for its ethical guidelines. As a result, the committee recently proposed new guidelines that came down much harder than previous versions on questionable practices related to the pharmaceutical industry. As was the custom, the proposed changes were put up on the web for public comment. Then in a couple of days, the draft was taken down, and the College announced that it was changing its procedure, to replace the open public comment period with an internal review; and apparently in the process the College also disbanded its ethics committee. It is not clear in the article whether this was a move intended directly to water down the strict guidelines against Pharma conflicts of interest, or just a move by a more corporate, and less professionally-minded organization to exercise tighter control over its own activities.

Update: What Drug Reps Know About Docs’ Prescribing—and Patients

A colleague just alerted me to a New York Times business article by Katie Thomas from last May:
http://www.nytimes.com/2013/05/17/business/a-data-trove-now-guides-drug-company-pitches.html?pagewanted=all
--which provides an update on the data that drug reps can download on the prescribing habits of the physicians they are selling to.

To briefly recap:

• The old old days: Drug reps would schmooze with the local pharmacist to get a sense of what docs were prescribing what drugs.
• The old days: Firms such as IMS Health would buy up prescription lists, in which physicians were identified by code number, and with patient names presumably redacted. The firms would then turn to the AMA and buy their master file of physician identifiers, allowing them to match the docs with the prescriptions they wrote. Before going into Dr. Welby’s office, the rep would download the records of how often Dr. Welby prescribed both the rep’s company’s drug and the competitor’s drug in the last month or so, with a lag time of about 1-2 weeks to get the data.

So what about today? Thomas reports that IMH Health recently bought out a firm called SDI Health, which is able to match insurance claim data with individual patients. Again presumably without divulging patients’ names (which would be illegal), these insurance data allow the rep to see the patient’s key health history, including lab tests and hospital admissions. This allows the rep to create a much fuller profile of when and on whom the doc prescribes that particular drug.

The article is somewhat complicated and notes several recent trends. First, Thomas reports that (good news for people like me), more and more docs are refusing to take time to see reps. Companies in cost-cutting moves have on their side laid off a lot of reps. So some of what drives this data searching is the felt need to be a lot more targeted once a rep is able to get a foot in the door.

But another trend noted is that a lot of this data-searching seems not to be about the rep-physician relationship at all; some claim that what is going on is how drug companies are marketing themselves not only to docs, but more to the big insurers, trying to show that the insurer would save bucks if they used more of a certain drug on certain groups of patients, or that some of their patients are going off their drugs too soon, or whatever.

The bottom line seems to be that drug marketing is the proverbial balloon which, pushed in at one spot, bulges out someplace else. You never hear of companies cutting back on marketing, maybe to go back into the laboratory and discover a new generation of true breakthrough drugs. Instead they stop marketing one way and spend even more money marketing in some other way, always trying to push their existing drugs, which far too often are merely more expensive without being any better or safer.

 

No Decency? Pharma-UK on How to Collaborate

While attending to events on this side of the ocean, I seem to have been late learning about a kerfuffle set off by the Association of the British Pharmaceutical Industry, which I gather is the UK equivalent of our PhRMA.

The ABPI last year issued a 4-page "Guidance on Collaboration between Healthcare Professionals and the Pharmaceutical Industry":
http://www.rcplondon.ac.uk/sites/default/files/guidance-on-collaboration_0.pdf
On its face this is quite an impressive document--it features the logos not only of ABPI but also such august organizations as the Royal College of Physicians, the Royal College of General Practitioners, the Royal College of Nursing, the British Medical Association, and The Lancet. It claims to have been produced by a conjoint effort of all these organizations "with the aim of promoting positive collaboration between industry and healthcare professionals to support high quality patient care."

Since The Lancet was prominently listed as a collaborator in this effort, several physicians actively critical of Pharma penned a letter to the editor of that journal which was published last July, regretting that the journal had allowed its name to be put onto a document that played fast and loose with the truth. Among the statements contained in the report that we have previously demonstrated to be either blatantly untrue or highly doubtful:

• "Healthcare and industry professionals are able to manage their relationships with each other without compromising clinical decision making."
• "Information about industry-sponsored trials is publicly available."
• "Industry plays a valid and important role in the provision of medical education."
• "[Industry] Medical representatives can be a useful resource for healthcare professionals."
• "The industry takes its responsibility to monitor adverse events very seriously."
• Anything negative about industry behavior in the past is solely due to "historical practices that are no longer acceptable, or the actions of a few individuals that are not typical of the working relationships between healthcare professionals and the industry."

And the report adds a list of "Dos and Don'ts for Healthcare Professionals"--

• "Don't establish blanket policies denying interaction with industry..."
• "Don't be tempted to accept the negative myths about cooperating with industry. Undertaken appropriately, working with industry will not harm objectivity..."

So-- how did The Lancet react to being challenged? Its editor, Richard Horton, published a revealing comment earlier this year, in which he retracted the journal's endorsement of the report: "The statements made in the 'guidance' certainly do not match  the latest evidence about the behavior of pharmaceutical companies today. Indeed, this evidence undermines the principles we originally signed up to, principles that attempted to forge a new and more constructive partnership between medicine and the pharmaceutical industry. It's time for us to withdraw our name from the 'guidance' as it currently stands."

A little bit of between-the-line-reading seems called for here. What I take Horton to be saying (based on past experience of similar efforts in the Pharma world) is that the ABPI invited all these other organizations to come on board by promising them that this time, the industry was really serious about finding new, more positive ways to collaborate, and perhaps indicating that they were finally ready to fess up to past wrongs and turn over a new leaf. Like Charlie Brown figuring that this time, maybe Lucy would actually hold the football for him to kick, those other organizations, all valuing the day (as I do, myself) when a real collaboration might become possible, signed on. And then, ABPI took advantage of its control over the writing process and inserted wording that served their PR purposes splendidly, but that were completely at odds with the cooperative spirit that had caused the other organizations to agree to become a part of the effort--in effect playing all the other groups for chumps.

The title of this post is taken from the incident in the Army-McCarthy hearings of 1954 which is usually cited as the turning point in the infamous career of Sen. Joseph McCarthy. With the nationally televised hearings not going the way McCarthy had hoped, he pulled out his usual trump card and without warning, accused a young lawyer in the firm of the Army's chief counsel, Joseph Welch, of once having been a member of a Communist-affiliated organization. Welch replied in defense of the lawyer and then, when the Senator continued his character assassination, turned on McCarthy with obvious regret, "Have you no sense of decency, sir? At long last, have you left no sense of decency?" It appears that Pharma-UK, offered a chance to finally show a sense of decency and admit that its past behavior has made it impossible for any health professional of integrity to trust them or to engage in any direct financial dealings with them, could not in the end change its stripes, but had to once again demonstrate its lack of decency and its insistence on substituting PR fluff for substantive change.

Braillon A, Bewley S, Herxheimer A, et al. "Marketing versus evidence-based medicine [letter]." Lancet 380:340, July 28, 2012.

Horton R. "Offline: falling out with pharma." Lancet 381:358, February 2, 2013.

Corporate Drug Pushers and Their Blame-Avoidance Techniques

I’m in the process of reading Deadly Medicines and Organized Crime: How Big Pharma Has Corrupted Healthcare, by the Danish trials expert, physician, and epidemiologist, Peter C. Gøtzsche. I hope soon to have a book report for this blog. In the meantime I am going to comment on a New York Times article that Dr. Gøtzsche cites and that I apparently missed first time around back in 2006:

http://www.nytimes.com/2006/01/28/national/28insulin.html?pagewanted=all&_r=0

Brief background: In early days pharmaceutical firms got insulin from pig and beef pancreas from slaughterhouses; that led to some problems with allergies. The next big advance was the ability to synthetically manufacture human insulin, which ended those problems. However, not content to stop there, various folks kept tinkering with insulin and came up with supposedly new and improved bioengineered forms, which are questionably better than plain human insulin, but of course are much more expensive. Gardiner Harris and Robert Pear summarized for the Times how Eli Lilly had at first cornered most of the U.S. insulin market, but that recently the Danish-based firm Novo Nordisk was trying hard to capture a good chunk of the market for its own products. In 2006 an investigation was going on to see if Novo Nordisk had crossed any legal lines in pushing their products.

The revelations Harris and Pear recounted (based on internal company documents they obtained) included how Novo Nordisk reps had paid “anchors” in doctors’ offices, usually nurses or medical assistants, to be on the lookout for patients taking insulin who could be switched to the Novo product, paying them on the basis of how many prescription switches they achieved—while all the while claiming that these folks were simply being paid to “educate” patients about diabetes.  Novo also contracted with the Rite Aid pharmacy chain to give them special discounts on their drugs in exchange for help switching patients in their database to Novo insulin, and were found to have paid at least one Rite-Aid pharmacist what seems to be a kickback for patients who were switched.

What I most want to focus on here are two documents unearthed in the Times article. The first was a memo that Vikki Tolbert, a Novo district manager, sent to her staff of sales reps in March 2004:

“Our goal is 50 or more scripts [switched] per week for each territory….If you are not achieving this goal, ask yourself if those doctors that you have such great relationships with are being fair to you. Hold them accountable for all the time, samples, lunches, dinners, programs and past preceptorships that you have provided or paid for and get the business!! You can do it!!”

This memo is great because it’s a laundry list of all the forms of bribes that reps pay to docs, and that when either the reps or the docs are challenged about them, insist that all these things are not bribes at all, but rather education, or else have some other fully legitimate purpose, and the last thing on the reps’ minds is that the docs are in any way beholden to them as a result of taking these things.  Here is as blatant a statement as I have ever seen that yes, it’s a bribe, pure and simple; if the docs take the money, they owe the rep the business in return.

So now we turn to Rite Aid. The corporation sent a letter to its pharmacists in February 2005, saying, “Each Novo Nordisk product we dispense brings us 20 to 40 percent better profit margin,” adding that these sales add millions of dollars to the corporation’s “bottom line.”

So what did Rite Aid have to say when told that one of its pharmacists was being paid by Novo to switch patients to their drugs? Well, of course they were shocked and had no idea that such a thing was going on.

Now, let’s back up a step. Last I heard, Rite Aid was a pharmacy chain, not a medical practice. I agree that pharmacists know a lot about drugs and it would be nice if physicians listened more to the advice that pharmacists could give them—as long as that advice was genuinely the pharmacists’ and not bought and paid for by the drug company. But bottom line is that doctors are supposed to prescribe drugs and the pharmacy is supposed to fill then script with the right drug, and help educate the patient about how to take it. If the doc has made a major error, such as prescribing Drug B to a patient already on Drug A where there’s a dangerous interaction between A and B, the pharmacist should call the physician immediately and warn of the problem—but that’s a far cry from switching equivalent drugs because Rite Aid makes a handsome bundle.

So the corporation is here sending a memo to pharmacists which is highly improper because it suggests a line of action that is quite contrary to the role of the pharmacy—but the company is simultaneously covering its own rear, so that if any pharmacist actually decides to cash in on this deal, and ask for an extra bonus from Novo for doing the switching, then the company can say it was all the fault of that one renegade pharmacist and had nothing at all to do with company policy.

Dr. Gøtzsche, in his intemperately titled book, more or less concludes that Big Pharma and everyone who’s in bed with them will say various things about their activities—and we cannot believe a single word of it because they routinely lie through their teeth. Maybe that’s a bit far even for a pharmascold like me to go—more on that when I get to the book review post—but from this particular set of examples, you can see where he’d get such an idea.

Diabetes, Drugs, and Cardiovascular Risk

The October 3 New England Journal features a “Perspectives” written by Drs. William R. Hiatt, Sanjay Kaul, and Robert J. Smith, all members of the FDA Endocrine and Metabolic Drugs Advisory Committee:
http://www.nejm.org/doi/full/10.1056/NEJMp1309610

The basic thrust of their piece is to defend the drug rosiglitazone (Avandia) from the accusations we’ve reviewed widely in this blog, that it causes excess cardiovascular risk. These authors appear to believe that when all the data are in, the risk has been overblown. (According to the on-line disclosure forms, two of the three have some financial ties to the drug industry, but this group does not appear to be overloaded with conflicts of interest so far as I can tell.)

They then proceed to discuss two newer diabetes drugs that have been subjected to extra scrutiny by the FDA, which is now gun-shy over diabetes drugs since the Avandia affair.  These newer drugs also appear to be reasonably safe in terms of not causing excess cardiovascular risks. But the flip side of that was that neither drug decreased cardiovascular risks, either, as one would hope for from a drug that treated a condition that is a major cause of cardiovascular disease.

In previous posts I have hammered on about one of the major consequences of drug industry marketing on diabetes:

http://brodyhooked.blogspot.com/2012/04/yet-more-on-broken-disease-model-of.html
--which is the promulgation of a flawed disease model among both practicing docs and the general public. We now have a lot of evidence that Type 2 (adult) diabetes should not be viewed primarily as “high blood sugar,” that drugs that lower blood sugar very well may be useless for preventing the downstream complications of diabetes. Yet drug industry and device marketing still finds the big bucks in pushing tight sugar control and close sugar monitoring.

So I find it worthwhile noting these passages in the “Perspective” by Drs. Hiatt, Kaul and Smith, and if they have financial ties to companies that make diabetes drugs, these passages are all the more impressive:

“From a cardiovascular perspective, rosiglitazone, saxagliptin, and alogliptin appear to be relatively safe. It is disappointing, however, that neither intensive glycemic control nor the use of specific diabetes medications is associated with any suggestion of cardiovascular benefit. Thus the evidence does not support the use of glycated hemoglobin as a valid surrogate for assessing either the cardiovascular risks or the cardiovascular benefits of diabetes therapy….New therapies targeting glycemic control may have cardiovascular benefit, but this has yet to be shown. The optimal approach to the reduction of cardiovascular risk in diabetes should focus on aggressive management of the standard cardiovascular risk factors rather than on intensive glycemic control.”

Let me translate a bit: Drugs that lower blood sugar have not yet been shown to prevent heart and blood vessel disease in adult-type diabetes. Treating Type 2 diabetes today should focus on proven methods for preventing such diseases, which is to lower cardiovascular risk factors. Simply showing that a drug lowers blood sugar says nothing about its value for preventing the serious complications of diabetes and should not be accepted by the FDA as a reason to market a new drug. And there you have it, from the (supposed) experts.