From Australia, A Gem of an Analogy

Roy Moynihan, the Australian journalist best known for his investigations of "disease mongering" by the drug industry marketers, recently did an interview show Down Under:

http://www.abc.net.au/rn/backgroundbriefing/stories/2008/2166307.htm

The theme of that program was how Australian GPs are tricked into attending continuing education conferences put on by companies that claim the programs are independent from commercial influence, when at the same time those companies are marketing their wares to drug firms by promising them a hand in choosing the speakers and topics so long as the drug firms fork over enough dollars.

That of course is old news, so what was in fact the high point of this interview, for me, came from Dr. Peter Mansfield of Healthy Skepticism, in this "Dang! I wish I had thought of that" analogy:

Peter Mansfield: I think the situation that we are in now is similar to in the 1840s, doctors didn't believe that we needed to wash our hands before we did surgery. We couldn't believe that we could be infected by something invisible that could cause harm to our patient. Bias that comes from promotion is like a bacteria in that it is invisible, and at the moment, if you suggest to a doctor that they could have become biased, many of us will take that as a personal insult, in the same way that doctors in the 1840s felt insulted by the suggestion that they could be carrying infections.

This great quote has it all--how a point of view can absolutely permeate the medical culture, and yet still be dead wrong; how physicians can unwittingly be a source of harm to their patients; and how the first natural, human reaction of physicians, when this is pointed out, is to be angry and insulted.

Dang! I wish I had thought of that.

Yet More Evidence of Data Suppression: A Play in Three Acts

We sort of have to walk through this one.

Act One: Irving Kirsch, a psychologist formerly at UConn and now in Hull, UK, is one of my heroes for his great work on the placebo effect and expectancy. Kirsch is also a person for whom the drug companies must keep a personal voodoo doll into which they regularly stick pins. Kirsch has enraged a lot of folks by doing detailed meta-analyses of all the data on the newer generation of anti-depressant medicines (the SSRIs and their relations, drugs like Prozac and Zoloft). He has shown in a couple of meta-analyses in the past that it is very hard to tell the difference between what these highly touted drugs do for depression and what happens when people take sugar pills.

His latest meta-analysis is: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045. Kirsch and colleagues here show that it appears that there is really a tiny group of depressed folks for whom the drugs show virtually all their effectiveness-- those with the most severe depression. If you have moderate or even somewhat severely depressed people, you can find no difference between the drug and the placebo group in the average clinical trial. Moreover, it is perhaps not even the case that for those most severely depressed patients, it is the drug that makes the difference. The trial results, Kirsch and colleagues point out, show rather that it's not that the drugs work better for those patients. It's that the placebos do worse. The difference between drug and placebo is therefore greater, but only because there is less placebo response, not because there is any greater drug response.

Act Two: Of course the companies are not about to stand still for any of this nonsense, so GlaxoSmithKline shot off a news release right away, claiming that Kirsch's analysis was flawed because he analyzed "only a small subset of the total data available." If true, this would be a serious charge against any meta-analysis.

Act Three: Along come journalists Jeanne Lenzer and Shannon Brownlee, writing in BMJ: http://www.bmj.com/cgi/content/full/bmj.39504.662685.0Fv1. They ask the $64 question-- if Kirsch and gang reviewed only a subset of all the data, how come? Kirsch for instance filed a request under the Freedom of Information Act to get all study data for 6 antidepressants from the FDA. The FDA then refused to release data from 9 out of the 47 trials that they identified as relevant--they still have not explained why those 9 trials were withheld. (It later was revealed that all 9 trials had shown negative results, indicating why the companies might not have wanted them to see the light of day.)

In other words, say Lenzer and Brownlee, GSK may in fact be quite correct that people like Kirsch cannot do a valid meta-analysis because they don't have all the data. But whose fault is that? How about the industry that has done its level best to suppress and conceal any trial data that looked to be bad for marketing, especially regarding antidepressants, as we have seen before:
http://brodyhooked.blogspot.com/2008/01/depressing-results-of-nejm.html

More on ENHANCE: Some On and Off Target Comments

The current issue of JAMA (subscription needed to access on-line) features a commentary by Drs. Philip Greenland and Donald Lloyd-Jones of Northwestern U. on the ENHANCE trial (about which see my post, http://brodyhooked.blogspot.com/2008/01/now-that-weve-been-enhanced-whats.html).

The result is sort of like Dick Cheney going quail hunting. You fire away with a shotgun, you shoot some things you wanted to, and maybe some things you shouldn't have.

On target: Two major conclusions about ENHANCE. First, the two docs are prepared to mince no words, and to declare flatly that there was no justification for ENHANCE at all except for company marketing. They argue that such studies simply should not be done, and their academic investigator colleagues should refuse to participate. Second, they point out that major organizations that tried to comment on ENHANCE, to help clarify the issues for the public, became tarred with the conflict-of-interest brush, and such organizations should take this seriously and divest themselves of such conflicts to be trustworthy in the future.

Drs. Greenland and Lloyd-Jones do not say if they are adopting their own good advice. The end of the article lists several significant conflicts of interest for each, with regard to statin manufacturers--which may be pertinent to what follows.

Off target: Here I have my own conflict of interest as I am under personal attack as it were. Drs. Greenland and Lloyd-Jones take great umbrage at the media response to ENHANCE, especially with regard to the suggestion that statins may not be all that they are cracked up to be in preventing heart disease. They regard this assertion as ridiculous and irresponsible and argue that physicians quoted in these "erroneous" media articles (like me) should really get out facts straight before shooting off our mouths. One of the two villainous articles they cite is the one by John Carey in Business Week: http://www.businessweek.com/magazine/content/08_04/b4068052092994.htm?chan=search

As I have tried to explain in this blog previously (http://brodyhooked.blogspot.com/2007/12/new-cholesterol-controversies-regaining.html), there is very good reason to doubt that statins are all that good especially for the primary prevention of heart disease (as opposed to secondary prevention, preventing future events in people who have already had hearty vattacks or strokes). Many of my colleagues whose work I rely on in reaching that conclusion were also interviewed by John Carey, and in my view he has a blockbuster lineup of experts that were all quoted in that article (not counting myself of course). Carey also did a fantastic job of explaining for the general public the difficult concept of "number needed to treat," which is the only intelligent way to make sense of most clinical trials research on drugs, so he deserves a gold star for great reporting, not the skunk cabbage that Greenland and Lloyd-Jones shove in his direction.

Greenland P, Lloyd-Jones D. Commentary: critical lessons from the ENHANCE trial. JAMA 299:953-55, Feb. 27, 2008.

Support DTCA Because It Leads to Bad Medicine?

I'm grateful to my pals Rick Bukata and Jerry Hoffman, of Primary Care Medical Abstracts, for calling my attention to this study, which I missed when it first came out.

Adam E. Block of Harvard set out to do a cost-benefit analysis of direct-to-consumer advertising (DTCA) of prescription drugs and chose depression as his test case. He concluded that DTCA is a wonderful thing. (He also explicitly denied having any conflicts of interest or receiving any industry funding.)

Here's the basic scoop--Block used a variety of surveys and studies to gather his data, and relied heavily on the Kravtiz et al. study that sent actors into phyysician's offices with different stories about DTCA, to see which ones got prescriptions. He figured out that DTCA would lead to massive overuse of antidepressants, with only about 1 out of 15 of those getting prescriptions actually being depressed. However, he also calculated that each depressed patient who takes a drug and gets benefit from it achieves such a gain in quality of life, that the improvements in that small group outweigh by far the costs of the drugs for the large group that does not need them.

Most understand that the problem with this sort of cost-benefit analysis is in the assumptions, and so Block quite responsibly subjects his findings to a sensitivity analysis. He claims that even fairly substantial shifts in his numbers would not change the final outcome; i.e. his results are reasonably robust.

Despite the sensitivity analysis, it is easy to spot serious holes in Block's model. For example, he assumes that antidepressants would be prescribed only for 60 days and so he calculates the cost of the drug on that basis. It is much more likely that an antidepressant, once started, would be prescribed for a year, if not indeed forever. Block also presumes that antidepressants have no side effects and so no patient's quality of life ever deteriorates as a result of taking one. I was not able to plug new numbers into his equation to see how changing these two assumptions would alter his results. As a final concern, he appears to assume that all patients who now have depression and yet are untreated have serious depression and so stand to gain substantially from therapy.

But for now, let's assume that Block's methods were impeccable and that his results hold water. On what basis would we recommend a policy of DTCA? It would seem, at least in the depression case, that we advocate DTCA because it leads to 15 patients with no depression being treated with a drug that they don't need, for every one patient with depression that gets the drug that truly is indicated. In short, DTCA should be recommended as good public policy because it results in abysmal medical practice by just about anyone's standard. (Block, to his credit, seems to have some sense of this and discusses the implications a bit at the end of his article; but overall he softpedals this major message.)

The obvious public policy question is how one could invest the resources now devoted to DTCA in such a manner that, instead of producing abysmal medical practice, one actually improved medical practice with regard to depression. It is hard to imagine that there is not a better approach than DTCA.

Block AE. Costs and benefits of direct-to-consumer advertising: the case of depression. Pharmacoeconomics 25:511-21, June 2007.

Kravitz R, Epstein R, Feldman M, et al. Influence of patients' requests for direct-to-consumer advertised antidepressants. JAMA 293:1995-2002, 2005.

The FDA's New Rule on Off-Label Marketing--Bad Idea

Previously I have offered opinions on why "off label" is a widely misunderstood category, and is often wrongly vilified:

http://brodyhooked.blogspot.com/2007/12/off-label-what-are-issues.html

So that must mean that I am OK with the FDA's proposed rules change...

http://www.nytimes.com/2008/02/16/business/16drug.html?scp=4&sq=gardiner+harris+f.d.a.+&st=nyt

...that would allow companies to start marketing drugs off label if they:

• Distribute to physicians only peer reviewed medical journal articles describing the proposed off label use
• Accompany any such article with a clear statement that the use described is not FDA approved

Right? Well, not exactly.

The point I tried to make in my earlier post is that even though many off label uses of drugs are quite defensible and are in the patient's interest, we need to be very wary of any specific rules change in the companies' favor, given their past ability to drive huge trucks through even the tiniest regulatory cracks.

The defenses for the new FDA policy, as summarized by Gardiner Harris in the NY Times, basically all amount to the same thing-- if there's scientific evidence that a drug works even off label, isn't it a good thing that docs see this scientific evidence as soon as possible? The answer is NO, not this way at least, for a bunch of reasons.

1. The most basic reason--if docs are too busy and harried to read the journals assiduously, why should they, as professionals, turn to a for-profit industry to help them? Why not develop a more professionally responsible and less commercially biased way to disseminate information quickly? (As in fact is now happening more widely.)
2. Why worry about for-profit bias? Often a single study will tell only a small piece of the story. For every study that shows a good outcome there might be one showing a bad outcome. How much can we rely on the industry to circulate both sorts of studies equally? Fat chance.
3. Now, the more subtle concern. We have seen mountains of evidence (HOOKED could have been twice as long had I included more of it) of companies fudging research results in more ways than you could name, to make a study come out as if the drug performed well and was safe, when the real data would show quite the opposite. The industry claims: we would never do that; we are scientific drug firms; we live or die on our spotless reputations; it is contrary to our commercial interests to put our names on garbage research. These claims have now been proven many times over to be bull. The companies can get away with garbage research because they know that the same busy docs that are too busy to read the journals carefully, are also too busy to read the entire article; they will be lucky to read the abstract. Spin the abstract so that the drug looks good, and you can have table after table of damning data in plain sight in the rest of the article, and most docs won't notice. Now, if the company knows that a research paper is going to be published in an obscure journal, where hardly any doc is going to see it, there is a certain amount of incentive both to fund the research in the first place, and to spin it in the second place. But if the company knows that its detail reps have free rein to push this article about off-label use under every doctor's nose, then the incentive to fund garbage research, and to spin it further, goes way up.

The new FDA rule proposal, therefore, is not a tiny crack through which the clever industry can drive the proverbial Mack truck. The opening is Mack-truck-sized from the get go.

Harris G. F.D.A. seeks to broaden range of use for drugs. New York Times, Feb. 16, 2008.

Supremes Strike Down Ability to Sue Over Devices

As explained in this New York Times coverage:

http://www.nytimes.com/2008/02/21/washington/21device.html?_r=1&ref=business&oref=slogin

...the U.S. Supreme Court handed the Bush Administration and the medical drug and device industries a major victory on Feb. 20, ruling that consumers injured by one class of medical devices had no right to sue in state courts because the devices had received FDA approval. (Other devices that had gone through a less arduous FDA review process were not covered by this ruling.)

That was the bad news. The other bad news is that the court ruling was 8-1, unlike the very common 5-4 split one sees on this nearly-evenly-divided (conservative vs. moderate) court.

The good news is that Congress could readily fix this by passing new legislation, and two foes of the drug industry, Sen. Ted Kennedy and Rep. Henry Waxman, vowed to do so.

The basic claim in the majority ruling is that the law assigns to the Federal government, and not to the states, responsibility for regulating devices and drugs. So for the states to allow such suits in their courts is tantamount to setting up a separate, illegal level of regulation.

The opposing argument, which in my view has more merit given today's realities, is that such a restriction on bringing suit against a company presumes a more or less perfect FDA process. It also assumes that there is really an adversarial relationship between the FDA and the manufacturer--that the FDA sets the bar deliberately high, and the manufacturer really has to come up with considerable and reliable proof that the device is safe and effective. More recently, especially with the FDA getting half of its budget for reviewing new drugs directly from industry, we have seen the FDA often serving as industry lapdog rather than as adversary.

As I mentioned in HOOKED, there is another angle on whether or not these lawsuits should be permitted. I'm a physician by training, and share with my fellow physicians the terror of a malpractice suit. Given this nearly instinctive distaste for using the tort legal system as a means to seek redress, how can I then turn around and say that it's a good thing when rapacious lawyers and clients can set their sights on the drug companies? One of the realizations that has led me to view such lawsuits with more sympathy is that without them, I could never have written HOOKED. That is, many of the most damning documents, that reveal the behavior of the drug industry that is most damaging both to public interests and to medical professionalism, come to light only as a result of the legal discovery process. The company can keep these nasty e-mails and memos secret, and only has to cough them up if it is sued. Without damage suits we would know a good deal less about the inner workings of the industry--to our great detriment.

Those who oppose such lawsuits naturally fear that the future will be bleak, as we and our children die of horrible diseases because no new medical drugs and devices are being marketed, because no company wants to face the financial risk of rampant lawsuits. That ignores the way that companies today seem quite undeterred even by huge class action suits. A company like Merck with Vioxx, or (earlier) Wyeth with the diet drugs fen-phen, simply stashes away in escrow a few billion dollars that it has rattling around in its pockets as spare change, as its lawsuit defense and payout fund. The company then reassures stockholders that it has stanched any future flow of red ink, and goes merrily about its business.

Greenhouse L. Justices shield medical devices from lawsuits. New York Times, Feb. 21, 2008.

Defending the Free Lunch: Mistakes Economists Make

One of my esteemed colleagues called my attention to a recent column by Emory University economist Paul H. Rubin:

http://www.forbes.com/columnists/forbes/2008/0225/026.html

Professor Rubin defends the free lunch and most every other form of drug company marketing, making the points:

1. For-profit competition is the best way of getting people to do useful things, including curing deadly diseases.
2. Drug company marketing is information, packaged in the most useful way for busy physicians to grasp.
3. If docs prescribe the most expensive, latest drugs, like drug reps want them to, their patients will benefit.

In short, God's in his heaven, all's right with the world, so long as Big Pharma rules.

Now, I had the honor to be on a panel with Professor Rubin at a conference last fall. He seemed a reasonably pleasant sort of fellow, though the "H" for his middle name does not stand for "humble." But one thing that became very clear in personal conversation with him is that he has complete faith in the research findings of business prof Frank Lichtenberg of Columbia, whose recent work he cites in his column. Lictenberg is the source of Point #3 in the above list, that more recent, more expensive, on-patent drugs produce better health outcomes across the board.

Readers of this blog and of HOOKED and related works might well wonder about such a sweeping claim. Has it not been shown that many recent drugs have serious, unanticipated side effects? Has it not been shown that the majority of recent drugs are really "me too" drugs with no advantages over older drugs? So how could Lichtenberg come up with exactly opposite conclusions?

I have read over several of Lictenberg's research papers, without having any skill at crunching numbers in the ways that economists do. I came to the conclusion that Lichtenberg is all wet. He simply does not know what he is talking about. He has no knowledge of what particular classes of drugs do and don't do in the human body, and seems not to have bothered to talk with anyone who does. So he has no clue when he is putting forth a proposition, based on economic modelling, that is biologically plausible, and when he is saying something that has no possible medical truth to it.

More recently, a detailed critique of Lictenberg's work has been done by people who do know how to crunch the numbers properly. I was privileged to read a draft of their work, and it is an even stronger indictment of Lichtenberg's conclusions than what I have written above. But as that paper is still under peer review for journal submission I cannot say any more about it.

Now, let me be very clear on one point. Some might conclude from this post that I am a typical physician who thinks that only doctors have any brains, and of course, if economists try to talk about medical issues, they will say stupid things. That is not my point at all. I could not have written portions of HOOKED had I not had the good fortune to work closely for several years with a couple of excellent health economists. But because we worked together as a team, I was at least able to warn them when they were making a mistake about some of the medical facts about how various drugs worked, for instance. Admittedly, they were generally very well informed and made few such mistakes. But at least they cared to be sure that they didn't; Lichtenberg seems oblivious.

So, if you buy into the world view that PhRMA and the drug industry tout, then all of Professor Rubin's points are unassailable. Prof. Rubin, a regular industry consultant, has bought it hook, line, and sinker.

Institutional Conflicts of Interest Policies: Some Assembly Required

The National Pharmaceutical Conflict of Interest Survey Factory (they're not really called that, it just seems that way), a.k.a. Eric Campbell and buddies, has published their latest study, this time on how many medical schools have adopted policies on institutional conflicts of interest (COI). Our national conflict-of-interest/professionalism guru, David Rothman of Columbia (Center on Medicine as a Profession), authored the accompanying editorial, making the points that far too few of the responding schools had institutional COI policies and predicting that government entities would probably step in to regulate the mess.

As I try to explain in HOOKED, institutional COI is a difficult problem to wrap one's head around. Individual conflict of interest (faculty member Dr. X owns stock in Pfizer and is PI on a big research study funded by Pfizer) is by contrast much easier to grab hold of. So for that reason alone it would not be surprising that more med schools would have individual COI policies compared to institutional COI. Nor is it surprising that many schools construe institutional COI to be a variant of individual COI--that is, do your president, trustees, and other highly placed officials individually own stock in companies, etc.?

When a problem is difficult to get a handle on, it helps to enumerate some concrete examples. Unfortunately, Ehringhaus et al. (that's the Campbell gang) did not, so far as I could notice, include any examples in their study report, so we are left to guess what sorts of instances they had in mind when they designed their survey questions. Rothman gives one key example, the 1999 Jesse Gelsinger case at Penn (subject dies in gene therapy experiment; university owns stock in the biotech company that would eventually market the therapy if it had worked). In HOOKED, I gave two other examples that are worth considering:

• The University of Toronto's reversal of its hiring of psychiatrist David Healy to run a research institute, after Healy gave a lecture viewed as unfriendly toward Prozac, when the University was hoping to land a major grant from Prozac's manufacturer, Eli Lilly
• UC-Berkeley's decision to virtually sell its plant biology department to Novartis, in exchange for first dibs on any patentable research produced by that department over a period of years

In asking whether a med school has an effective institutional COI policy, we'd have to ask what the policy would say, for example, about each one of these three arrangements (which hardly exhaust the possibilities but are at least a place to start). It seems clear that Ehringhaus et al's survey addressed cases like Gelsinger and Toronto; it's not as clear to me that the Berkeley case would be covered by one of their categories. (I'd assume that the money to run the department was classed as a grant and not as a "gift.")

Two points need to be made in summary:

• It is not clear to me what one can do about institutional COI when the forces working on the average medical school are aligned as they are today. Basically a med school dean is under tremendous pressure to bring in commercial sources of research support. NIH dollars are drying up as fast as subprime mortgages are imploding; and the going buzzword (I'll pay a reward to anyone who can explain to me what it means in plain English) is "translational research," which means that research results must be moved much more quickly "from bench to bedside," which seems to be a directive to med schools to jump into bed with industry even faster and deeper (I think that is what "translational research" means in plain English). Exactly what is a paper policy supposed to do in the face of that perfect COI storm?
• In HOOKED I cite the conclusion of some Canadian thinkers on this matter who no doubt have carefully pondered the Toronto example. They offer the conclusion that there is simply no such thing as an institutional COI policy so long as there is no body outside of and above the university to whom concerns can be referred or appealed. Exactly who at Berkeley was supposed to have decided that selling the plant biology department to a private company was an institutional COI, given that everyone from the President to the Dean on down was obviously salivating at the dollar signs? I have yet to see an institutional COI policy in the US that addresses the incredible difficulty of an institution policing itself in such matters, and that suggests how such an extra-institutional appeals board should be created. (For med schools it would presumably have to be a creature of the Association of American Medical Colleges (AAMC). For universities in general--who and where?) Without some enforcement mechanism with teeth, that resides outside of any individual university or med school, I will continue to regard any institutional COI policy as nice window dressing (a somewhat harsh overstatement but only slightly). Indirectly that backs up Rothman's perediction that the government is probably coming, whether we like it or not.

Ehringhaus SH, Weissman JS, Sears JL, Goold SD, Feibelmann S, Campbell EG. Responses of medical schools to institutional conflicts of interest. JAMA 299:665-71, Feb. 13, 2008.

Rothman DJ. Academic medical centers and financial conflicts of interest. JAMA 299:695-97, Feb. 13, 2008.

Science by Press Release? More Evidence of Commercial Control of Research

The best way to do this post is in 3 parts.

Part One: Recently the ACCORD study of tight control of Type II diabetes was stopped prematurely, due to the unexpected result of excess risk of death in the group with tighter control:

http://www.chron.com/disp/story.mpl/headline/nation/5520313.html

I was contacted by a reporter to comment, and I gave the poor guy an earful about how the lack of benefit of tight control in preventing vascular complications of Type II diabetes had been amply proven in the past, so that at least the lack-of-benefit part, if not the actual added-harm part, was no surprise. (And it was very odd that the so-called national experts on diabetes, when interviewed by the media, acted like it was.) The major study to show the lack of benefit of tight control for preventing major diabetes complications was the United Kingdom Prospective Diabetes Study (UKPDS) which followed a large group of diabetic patients (Type II, remember) for 10 years and is probably the largest-scale study of Type II diabetes outcomes that will be done in my lifetime, at any rate.

Part Two: The intrepid reporter e-mailed me earlier today to ask whether I had altered my opinion, in light of a press release he had received from these folks:

http://www.thegeorgeinstitute.org/

The George Institute for International Health. You've heard of them, right? They're right up there with Harvard and Johns Hopkins and NIH and Mayo Clinic as one of the great centers for medical research, right? (Well, maybe not.) They happen to be located in Australia.

Anyway, the press release was not on their website when I just checked (I am guessing it will appear in the next day or so), so basically what it says is that thse guys are doing a study called ADVANCE, involving 11,140 diabetics, to test the effects of tight control of both blood pressure and blood sugar. The blood pressure results (which show a slight reduction in complications with tighter control, no surprise there) were published in Lancet, September 14, 2007. The tight blood sugar control part of the study is nearly complete.

What the George Institute wanted us to know right away, via the press release, is that their data safety and monitoring board for ADVANCE had snooped into the data (as they are supposed to), even though the study is not yet complete, and that they were very pleased to report that ADVANCE has not found what ACCORD did-- that is, there was no excess risk of cardiovascular complications in the tight control group.

Part Three: This is the e-mail message I sent back to the reporter, with my comments on all the above:

If a group of scientists (#1) are doing a study, and another scientific study (#2) is published that shows certain results, and the scientists doing study #1 are quite sure that their study will show different results, it is in my experience extremely unusual that group #1 would send out a press release to announce this. Rather, it would be the usual practice to wait until the results of #1 had received the usual scientific peer review, and been accepted for journal publication, before any publicity would go out.
Sending out press releases fast and furious, on the other hand, is SOP for companies trying to sell drugs.
I looked on the George Institute website and it appears that they are heavily funded by drug companies. (Just how much is not clear from their financial statement as they do not break their funding sources down by commercial vs. non-commercial.)
I note that the drugs being used in the ADVANCE study are all, apparently, new, brand name drugs that are probably "me too" drugs that closely resemble in their actions older, generic drugs that are considerably cheaper and whose side effects are much better elaborated. A study that looks at new, expensive brand-name drugs in preference to more widely used drugs is often a commercially funded study designed primarily to push the new drugs.
All those things will make me view the results of ADVANCE with considerable suspicion, once we actually know what the results are.
Now, let me take the press release at face value. ACCORD showed basically two things, 1) that tight glucose control was of no benefit to diabetics, and 2) that tight glucose control could actually have caused harm. So far as I know, #2 is a new result, and could easily be a statistical fluke. One danger of stopping a study early is that a statistical fluke could be responsible for your finding, and only by carrying on the study longer would you find out that it was a fluke and not real. (Now, I have to add a qualification here. One known risk of trying too aggressively to lower blood sugar is to cause excess cases of low blood sugar (hypoglycemia), which can be damaging to one's health. So it would not be unexpected that hypoglycemia appeared as a downside in any study that aimed at aggressively tight glucose control. I did not mention this initially because based on what we know so far of ACCORD, it was not clear that hypoglycemia was the means by which the adverse results apparently occurred.)
On the other hand, when I told you at first that one could have predicted the results of ACCORD based on the previous experience of the UKPDS trial, I was referring to #1, that is, the lack of benefit of tight control. I find it interesting therefore that the ADVANCE press release makes no claim whatever that they found benefit-- merely that they did not find harm. If indeed the ADVANCE group is heavily drug company funded, the SOP would be to do their best to spin whatever data they get, to make it seem as if there is a significant benefit to tight control using their expensive, preferred drugs, even if there is not. Sorry if that sounds cynical but it is just what we have recently seen in the ENHANCE trial of lowering cholesterol, and other previous occasions too numerous to list here.
ADVANCE has also showed, so far, according to the press release, that lowering blood pressure in diabetics helps reduce the risk of complications. This is old news and fully predictable by UKPDS. The favorable result also could have been achieved with old, generic drugs and would not require expensive brand-name drugs.

Nurses: "Soft Targets" for Pharma Marketing?

New ground is broken by Annemarie Jutel and David Menkes of New Zealand in their paper:

http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050005

Given the increasingly strident and extensive debate occurring in the medical literature about physicians and pharmaceutical marketing, the authors wondered what was going on in the nursing literature. After an extensive search they identified only 32 articles, including empirical studies (only 7), editorials, comments, and opinions.

They found a number of causes for concern:

• Nurses seem timid in criticizing industry marketing practices. A paper that finds many reasons to condemn (for instance) DTC advertising, then feels a need for "balance" and so proceeds to list all the favorable aspects of DTC.
• When nurses write opinion pieces sharply critical of the industry, the editor of the journal often feels a need to soften the impact by printing a dismissive reply, or by appending a defense of the industry from an industry rep.
• An undercurrent that runs through many articles seems to go roughly as follows: physicians, of course, are evil beasts, so it is no surprise that they fall prey to industry marketing blandishments. Nurses, by contrast, are ethically far superior to docs, so there is no way that they would be similarly seduced. This belief in the ethical purity of the nurse is maintained despite 1) all the data showing that physicians similarly feel immune and yet are easily swayed; 2) the absence from the nursing curriculum of any formal courses warning nurses about the dangers of marketing messages; and 3) the similar absence from the nursing curriculum of courses such as critical appraisal of the literature, biostatistics, and other material that would enhance their ability to review marketing information with proper skepticism.
• An even more worrisome undercurrent in a few articles that says, how come docs get all the goodies; what are nurses, chopped liver? How come we don't get our fair share of the bribes? (Especially from nurse practitioners with prescribing privileges)

The concluding paragraph of the paper is worth quoting in full (cites omitted):

The pharmaceutical industry recognises nursing influence on medical prescribing and identifies nurses as a marketing target. The industry has had its eye on nurses and nurse practitioners for over a decade, and is heavily invested in wooing them. Unfortunately, its success in this area has been at the expense of the health budget, evidence-based care, and nursing integrity. All three can and must be reclaimed.

Nurses historically have many legitimate grievances against the medical profession. It would be very sad indeed if nursing allowed those grievances to blind them to the real dangers to their professional values posed by pharmaceutical marketing and "gifts."

Jutel A, Menkes DB. Soft targets: nurses and the pharmaceutical industry. PLoS Med 5(2):e5. doi:10.1371/journal.pmed.0050005