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 More Arguments for Withholding Crestor [21:30m]: Play Now | Play in Popup | Download (93)

DrRich’s last post addressed a recent issue of the Archives of Internal Medicine which, strikingly, was largely dedicated to trashing the JUPITER study.

The JUPITER study was a landmark clinical trial in which giving the statin drug Crestor to apparently healthy individuals who were at increased risk of cardiovascular disease (and most particularly, had high CRP levels) resulted in a significant improvement in outcomes. In particular, within two years, individuals taking the statin had a 20% reduction in overall mortality, a 54% reduction in heart attacks, a 48% reduction in stroke, and a 40% reduction in venous thrombosis and pulmonary embolism. All these findings were highly statistically significant.

DrRich attempted to show that the criticisms of JUPITER recently offered by the Archives were sufficiently spurious to raise the question of what the authors and the editors were really trying to accomplish, and for him to suggest that perhaps they were auditioning for appointments to the government’s expert medical panels, which will soon begin determining who gets what, when and how. Indeed, DrRich will actually be quite surprised if none of these individuals end up with such an appointment. They have clearly demonstrated they have the right stuff.

Still, as DrRich also pointed out, the JUPITER study, while a reasonably straightforward clinical trial whose results seem impressive, was anything but air-tight. No clinical trial is air-tight, however, and if medicine were still practiced the way it should be, the JUPITER trial could be smoothly incorporated – with all its limitations – into clinical practice without a hitch.

But, since medicine is now practiced by guidelines, JUPITER poses a major problem. In fact, it has led to major and contentious debates between those who insist its results must be incorporated into formal clinical guidelines, and who insist they should not. On one hand, many point out that JUPITER is an important clinical trial which has demonstrated a vital clinical benefit (prevention of heart attack, stroke and death) with a high degree of statistical significance, which meets the high standards demanded by evidence-based medicine, and which therefore obviously demands a change in the clinical guidelines. But on the other hand, many others insist that the JUPITER trial simply does not demonstrate enough of a benefit with Crestor to justify changing the guidelines.

DrRich’s position – that the results of the JUPITER trial are striking and important but incomplete, and ought to change the conversation between, but not dictate the actions of, doctors and patients – simply does not obtain in the modern era.

So, unable to side with either party, DrRich observes with great interest the debate between those who want to change the guidelines, and those who believe that changing the guidelines would be the greatest of travesties.

Those who want to change the guidelines have, in their favor, the virtue of consistency. For, if one insists that every action by physicians must be supported by evidence-based medicine, then one is pretty much obligated to fully embrace legitimate clinical trials like this one that give clear-cut and statistically significant results. Unfortunately, the evidence-based strict-constructionists have painted themselves into a corner when it comes to JUPITER. They will not be able to say, for instance, “Statins are pretty much alike, so we’ll make the guidelines say ‘statins’ instead of ‘Crestor.’” For JUPITER did not study “statins,” it studied only Crestor, the most expensive statin on the planet. Expanding the results to all statins (despite a large body of experience that suggests this would be just fine) does violence to the whole concept of evidence-based medicine. It’s just not possible. The strict constructionists have therefore boxed themselves in to advocating a new, multi-billion dollar annual expenditure.

It is even more amusing to observe those who do not want to change the guidelines.

These people fall into two general camps. First, and easier to dismiss, are those who believe that drug companies are the embodiment of evil, and that any clinical trial sponsored by a drug company must be dismissed out of hand, particularly if the drugs which are being promoted are statins. (This, in fact, is the level of argument on which the main article in the recent issue of Archives relies.)

DrRich simply notes, once again, that the advancement of clinically useful medical science – in America and in the world – is almost entirely dependent on drug companies and other corporate dens of iniquity. That companies must pay for our medical research is the system we’ve invented. Furthermore, our total capitulation to the dictates of evidence-based medicine means that companies must fund large, expensive clinical trials like JUPITER before they are allowed to sell a new product, or to create a new indication for an old product. This evidence-based paradigm is inherently a double-edged sword. Sure, it creates a huge barrier to the development and adoption of expensive new therapies (which is the covert rationing dividend of evidence-based medicine), but it also creates opportunities, for companies who manage to successfully complete such trials, to create iron-clad indications for their products. For, once a product has been “proven” in a randomized clinical trial, there is no easy way to legitimately keep that product out of the guidelines and off the shelves. The makers of Crestor have simply figured out the rules. One can whip up anti-corporate emotions by criticizing the sponsor for playing the game well, but the fact that the sponsor stands to gain does not negate in any way the results of a well-designed study.

That the anti-pharmaceutical and anti-statin crowds vociferously object to the results of the JUPITER trial is, of course, entirely expected and cheerfully acknowledged. DrRich will merely observe that their position is one of default. It is not dependent on the scientific merit of JUPITER (or any company-sponsored study), and thus it adds no useful information to the debate. We can only note their objections and move on.

The second group of people who object to changing the guidelines are less dogmatic and more open to reason, and indeed (and very interestingly so) claim to be proponents of evidence-based medicine, and thus claim to be willing to follow the data to where it will lead. It seems pretty clear (to DrRich, anyway), that the chief concern of these individuals, as it relates to JUPITER, is cost. That is, this group feels strongly that the implications of the JUPITER trial are simply too costly to follow to their logical conclusion. This, indeed, is a very reasonable position to take.

Unfortunately, the only legitimate way to turn aside the results of a costly but statistically definitive, evidence-based study is by rationing healthcare. (To ration, remember, is to withhold at least some useful medical services from at least some people who would be likely to benefit from those services.) But we can’t do that, because, well, it would be rationing. Because members of this second group are unable to invoke the “r” word, they are therefore forced to find other “reasons” for keeping the guidelines unchanged. This unfortunate situation leaves them little choice but to discover ways in which to impugn the legitimacy of the JUPITER trial.

In short, they find themselves forced to engage in statistical legerdemain in order to diminish the significance of the JUPITER trial. There are several useful statistical arguments they can employ.

From what DrRich has seen, many of the arguments that have been ginned up to this end have not come directly from the JUPITER trial itself, but instead from an editorial accompanying this study, written by Dr. Mark A. Hlatky.

Most of Dr. Hlatky’s editorial is measured and reasonable. But he threw in a key summary sentence that has been greedily grasped by the anti-alter-guidelinetarians, to wit: “The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin [Crestor] group; thus, 120 participants were treated for 1.9 years to prevent one event.”

This statement, at least taken at its face value as a stand-alone analysis, is statistically naive and wrong. DrRich realizes that one or two of his readers might not enjoy statistical arguments, so if you do not wish to wade through the reasons why, simply skip the next two indented paragraphs.

In a long-term clinical study in which the endpoints are events that can occur at any time (such as heart attack, stroke or death), then the probability that an enrolled patient will reach an endpoint in the trial increases the longer he/she has been enrolled in the trial. But in virtually all clinical trials, the length of time different people are enrolled varies greatly. This is because it often takes years to enroll people in clinical trials, so that when the trial ends, some will have been in the trial for many years, others for only a little while. This means that the risk exposure of each research subject is different, and is proportional to the total time they were enrolled. Not uncommonly, the enrollment process is not smooth – there are periods of more rapid enrollment, and periods of slower enrollment – so if all you do is average the enrollment time (as was done by Hlatky – 1.9 years) you are likely to get skewed results. So it is simply not statistically legitimate to do so.

There is a legitimate way of analyzing such longitudinal outcome statistics, and it’s called the Kaplan-Meier method. And indeed, the authors of the JUPITER trial presented in their paper a complete Kaplan-Meier analysis of their data (see Figure 1 of their paper), and the results look quite a bit different from Hlatky’s summary statement. The Kaplan-Meier analysis reveals that the risk of heart attack, stroke, and death all increase steadily through at least 4 years (5 years was the longest time anyone was enrolled in this study), so that at 4 years, the risk of reaching one of the “cardiovascular event” endpoints was about 8% (not 1.8%). Further, the Kaplan-Meier analysis shows that the protection imparted by Crestor persists through at least 4 years, and that indeed the magnitude of protection (i.e., the difference in outcomes between the treated group and the placebo group) increases throughout that entire duration. So, at 4 years, the placebo group had roughly an 8% event rate, compared to roughly a 3% event rate for the Crestor group – an absolute difference of about 5% (not 0.9%). This is a far greater benefit than is suggested by Hlatky’s shorthand summary.

Suffice to say, then, that Hlatky’s summary statement apparently ignores the appropriately analyzed data which is clearly presented in the JUPITER paper itself, and which documents that the clinical benefit of Crestor was substantially more impressive than his widely-quoted summary statement suggests.

But as illegitimate as this summary statement may be, let us accept it at face value for a moment just for the sake of discussion, since that’s the data the anti-alter-guidelinetarians have latched on to.

Taking these numbers, the “antis” make the following argument: While the relative reduction in “hard cardiac events” is 50% (1.8 to 0.9), the absolute reduction is only 0.9%, which, anyone would agree, is a pretty small number. So, they conclude, the actual benefit imparted by Crestor is actually quite small.

That’s a very interesting argument. Let’s look at it in a couple of ways.

So we’ve got a population of patients whose risk of heart attack, stroke, bypass surgery/stenting, or death is about 2% at about 2 years, and by giving them a pill we can reduce that risk to about 1%, and we’re arguing that the absolute drop of 1% is not very much to crow about. Well, OK. But what if we found a pill that reduced their risk to zero at 2 years? That is, it completely wiped out the risk of cardiovascular catastrophes altogether. Would that be a good thing? Or would we say, “It’s just a 2% drop, really not much greater than the 1% drop we had with Crestor, so it’s no big deal?” DrRich thinks not. DrRich supposes we would think that totally eliminating all cardiovascular risk would be a very big deal.

When you’re starting at a 2% risk, then any drop in risk is going to be an “absolutely” small number. And if we’re not going to pursue improvements in outcome of such a small magnitude, then why the heck are we worrying about preventative medicine in the first place? Once you get past the big things (drain the swamps, don’t drink the water downhill from the outhouse, etc.) then all preventative medicine tends to consist of small, incremental improvements in outcome. Popular pronouncements to the contrary notwithstanding, preventative medicine is largely the art of spending a lot of money for this kind of incremental improvement. If we decide we shouldn’t do this anymore, then DrRich would find it unfortunate but understandable. But it hardly seems reasonable to arbitrarily focus on this one, particular improvement in preventative cardiology, and (within a healthcare system that insists it is not rationing care) pronounce that this is the one we’re not paying for.

Another way of looking at this “the benefit is too small” argument is by considering that 7.4 million Americans fit the entrance criteria for JUPITER. By giving all these people a statin, we would be preventing about 66,600 major cardiovascular events over a 2 year period. If you’re going to say that 1% is a small number, DrRich will counter that 66,600 is a big number. So do statins offer a substantial benefit or not? It depends on whether you choose to focus arbitrarily on the 1% or the 66,600.

(DrRich understands that many of his readers are not focusing at this moment on the 66,600 cardiovascular catastrophes that could be prevented, but on the 7.4 million people who will be taking a drug that costs $120 per month. But we’re not talking about cost yet, we’re only talking about whether the drug does some good. If we decide it does, then we’ll need to link that “good” to a procedure that measures whether the “good” is worth the money we would need to spend to achieve it. The “antis” try to avoid talking about cost – since that would admit they’re rationing – by insisting that there’s just not enough “good” to bother with. DrRich is simply pointing out that such an argument – that preventing 66,600 very bad outcomes is not enough to bother with – is on its face absurd.)

Another argument invoked by the anti-alter-guidelinetarians is based on the “number needed to treat” (NNT) analysis. Again they rely on Hlatky’s unfortunate summary of the data: “120 participants were treated for 1.9 years to prevent one event.” This number – which the “antis” insist is just too high – is misleading for the reasons already discussed. The real NNT, based on more legitimate statistical analysis, is plainly laid out in the JUPITER paper itself. It turns out that the longer patients in this trial were treated with Crestor, the lower the NNT became. So: At 2 years, the NNT was 95; at 4 years, it was 31; and at 5 years, it was projected to be only 25. Whether you think it is reasonable to treat 25 people with a pill for 5 years to prevent one of them from having a heart attack, stroke, or death is, DrRich supposes, a matter of opinion. But based on NNT analyses for many widely-accepted therapies in medicine today, it looks pretty good.

All these arguments, of course, are merely distractions. The fact is that JUPITER showed a pretty striking reduction in nasty cardiovascular events over s pretty brief period of time, and the only real reason there’s any controversy at all is because of the cost of Crestor.

That cost is what makes us want to withhold Crestor, even though it is imparting at least some (and, DrRich, argues, quite a bit of) clinical benefit. In other words, the high cost makes us want to ration Crestor. The fact that we can only ration covertly, instead of openly, is what makes us want to bastardize the science and do a Kabuki dance with the statistics.

If we were rationing healthcare openly, then we could do an objective, full-bore cost-benefit analysis on the use of Crestor in JUPITER patients, using legitimate and not ginned-up statistical analysis, and taking into account not only the cost of the drug, but also the cost that would be incurred by failing to stop preventable heart attacks, strokes, etc., and then determining where the overall cost-benefit result fell within our coverage criteria. If it met the criteria we would cover it, if not, not. This decision would not be arbitrary. It would be a fully transparent process, so that if the sponsor did not like the results, they would try diligently to find a way to reduce the cost of Crestor (DrRich thinks they would succeed) to a value that would be compatible with their staying in business. (And for the first time, the price of medical products would be determined by a Laffer-like curve, where a price that was too high – like taxes that are too high – would reduce revenue, instead of increase revenue. Companies, being fairly rational, would ratchet their prices down to the optimal price point.)

But since we insist on doing our rationing covertly, DrRich is sorry to say that we’re destined to keep making spurious arguments, and using dumbed-down statistical analysis to back them up. The JUPITER trial, while it is imperfect and while it does not answer every question, really is pretty straightforward. That we get so wrapped around the axle trying to fold such clinical trials into our covert rationing paradigm is simply another demonstration of the fact that covert rationing corrupts everything it touches.

________________________________

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DrRich explains it all in, Fixing American Healthcare – Wonkonians, Gekkonians and the Grand Unification Theory of Healthcare.

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 Why They're Trashing the JUPITER Trial [17:44m]: Play Now | Play in Popup | Download (57)

This week, the Archives of Internal Medicine published four (four!) articles assaulting the legitimacy and the importance of the JUPITER trial, a landmark clinical study published in 2008, which showed that certain apparently healthy patients with normal cholesterol levels had markedly improved cardiovascular outcomes when taking a statin drug.

Superficially, at least, the JUPITER study appears to have been pretty straightforward. Nearly 18,000 men and women from 26 countries who had “normal” cholesterol levels but elevated C-reactive protein (CRP) levels were randomized to receive either the statin drug Crestor, or a placebo. CRP is a non-specific marker of inflammation, and an increased CRP blood level is thought to represent inflammation within the blood vessels, and is a known risk factor for heart attack and stroke. The study was stopped after a little less than two years, when the study’s independent Data Safety Monitoring Board (DSMB) determined that it would be unethical to continue. For, at that point, individuals taking the statin had a 20% reduction in overall mortality, a dramatic reduction in heart attacks, a 50% reduction in stroke, and a 40% reduction in venous thrombosis and pulmonary embolism. All these findings were highly statistically significant.

This study is noteworthy because it is the first large randomized trial to show that taking a statin can markedly reduce the incidence of some very nasty cardiovascular outcomes in people who are considered to have “normal” cholesterol levels. (Notably, typical LDL cholesterol levels among primitive hunting/gathering cultures is around 50 mg/dL, instead of the 100 – 120 mg/dL we consider to be normal. These primitive folks have an extremely low incidence of cardiovascular disease, so maybe humans’ optimal cholesterol level is much lower than we now think. On the other hand, the low risk of cardiovascular disease among hunters/gatherers may instead be related to the fact that many of them are consumed by various species of carnivores before they’re 30.)

To be sure, the JUPITER trial was far from perfect. Because of its design, it could not (and did not) tell us whether the beneficial outcome is specific to Crestor, or is a class effect of all statins (which seems very likely). It did not tell us whether reducing CRP levels is itself beneficial, or even whether using CRP as a screening tool is actually helpful. (The people enrolled in this trial tended to have several other risk factors, such as being overweight, having metabolic syndrome, and smoking, and it is not clear how much additional risk elevated CRP levels really added in this population.) And this trial did not tell us the risks of lifelong, or even very long-term, Crestor therapy.

But JUPITER did tell us something that is very useful to know, and with a very high degree of statistical surety: Giving Crestor to patients similar to the ones enrolled in this study can be expected to result in significantly and substantially improved cardiovascular outcomes, and in a relatively short period of time.

If medicine were practiced the way it ought to be – where the doctor takes the available evidence, as imperfect as it always is, and applies it to each of her individual patients – then the incompleteness of answers from the JUPITER trial would present no special problems. After all, doctors never have all the answers when they help patients make decisions. So, in this case the doctor would discuss the pros and cons of statin therapy – the risks, the potential benefits, and all the quite important unknowns – and place the decision in the perspective of what might be gained if the patient instead took pains to control their weight, exercise, diet, smoking, etc. At the end of the day, some patients would insist on avoiding drug therapy at all costs; others would insist on Crestor and nothing else; yet others would choose to try a much cheaper generic statin; and some would even opt (believe it or not) for a trial of lifestyle changes before deciding on statin therapy. In other words, there is a range of reasonable options given the limitations of our knowledge, as there often is in clinical medicine. As time goes by, more scientific evidence is often brought to bear and clinical decisions can become more informed. But whatever the state of the evidence, doctors and patients can generally get by without violating too severely any ethical or medical precepts that would cause objective and neutral observers to complain very much.

But in recent years, and especially now, as we bravely embark on our new healthcare system, this is not how doctors will practice medicine. Instead, they will practice medicine by guidelines. These guidelines (which, in modern medical parlance, is a euphemism for “directives”) are to be handed down from panels of experts, identified and assembled by members of the executive branch of the federal government.

And this makes the stakes very high when it comes to a clinical trial like JUPITER. For guidelines do not permit a range of actions tailored to fit individual patients (consistent with the uncertainties inherent in the results of any clinical trial). Instead, guidelines will seek to take one of two possible positions. That is, under a paradigm of medicine-by-guidelines, the results of clinical trials generally cannot be permitted to remain imperfect or nuanced or subject to individual application, but must be resolved by a central panel of government-issue experts into a binary system – yes (do it) or no (don’t do it). In the case of JUPITER, the guidelines must decide whether or not to recommend Crestor to patients like the ones enrolled in the study, at a potential cost of several billion dollars a year. It should be obvious that the answer which would be more pleasant to the ends of the central authority, and  by a large margin, would be: No, don’t adopt the JUPITER results into clinical practice.

However, the expert panels which are called for by our new healthcare legislation have not been formulated yet, and we are still operating under the “old” rules. So, still subject to all the duress which is created by unfortunately-resolved clinical trials like this one, the FDA, somewhat reluctantly, approved the use of Crestor for JUPITER-like patients in late 2009. That approval, of course, is subject to review by the new expert panels, whenever they are assembled.

This, DrRich submits for your consideration, is likely what instigated the almost violently anti-JUPITER issue of the Archives this week. DrRich theorizes that what we’ve got here is a bunch of wannabe federally-sanctioned experts, auditioning for positions on the expert panels. What better way to get the Fed’s attention than to let them know that you are of the appropriate frame of mind to assiduously seek out scientific-sounding arguments to discount the straightforward and compelling, but fiscally unfortunate, results of a well-known clinical trial?

Of the four papers appearing in this week’s Archives, three are more-or-less legitimate academic articles that make reasonable points, but do no harm to the main result of JUPITER. The fourth is a straightforward polemic, which has no place in a peer-reviewed medical journal, and whose very presence, DrRich believes, very strongly suggests that the editors of the Archives themselves must be auditioning for the Fed’s expert panel.

So as not to bore his readers any more than necessary, DrRich will make short work of the three reasonably legitimate articles in this issue. One pointed out that JUPITER did not tease out the real importance of CRP levels, or whether lowering those levels is useful. This is true, but that fact does not touch the main conclusion of JUPITER. Another article was a meta-analysis which incorporated several other primary prevention trials using statins, and concluded that there is no overall benefit to statins in primary prevention patients. Aside from the usual problems inherent in meta-analyses, a) the JUPITER study looked at a specific population of primary prevention patients not addressed by these other studies, and b) since JUPITER is the first study to show a benefit in using statins for primary prevention, it is a foregone conclusion that if you assemble enough of the previous, negative studies and lump them together with JUPITER in a meta-analysis, you will be able to dilute the results of JUPITER sufficiently to achieve an overall negative result. Actually doing such a meta-analysis, then, is merely an exercise in math, not in revelation.

The third article criticized the JUPITER DSMB for stopping the trial earlier than originally planned. The DSMB, however, had no real choice in the matter – ethically or legally – given the striking statistical significance of the benefit seen with Crestor. When a patient signs an informed consent agreement to participate in a clinical trial, part of that “contract,” a part required by law, is the statement to the effect that if information comes to light during the course of the study that might impact a patient’s willingness to continue participating, that information must be made available. The fact that the Crestor branch of the study was found to have markedly improved survival, fewer strokes and heart attacks, etc., than the placebo branch, clearly constitutes such information. Stopping the study when they did was not “premature;” continuing the study would have been illegitimate. This is why independent DSMBs exist in the first place – to protect the rights and welfare of the research subjects under the fiduciary agreement that comprises informed consent.

The fourth article is more striking (and more fun) than the other three. Interestingly, it is categorized by the Archives as an “Original Investigation,” despite the fact that it describes no investigation of any kind whatsoever – original or derivative. It merely revisits the data from JUPITER (in a spectacularly biased manner), and offers a spate of ad hominem attacks, alleging bias to the point of corruption, without any supporting evidence, against JUPITER’s sponsor, its investigators, and most astoundingly, the chair of the DSMB (who is a well known and highly respected figure, especially known and revered for his complete objectivity and lack of bias). If such an article has any place at all in a peer-reviewed medical journal – which DrRich doubts – it ought to be clearly labeled as an opinion piece, and not as a piece of original research. Whatever it may be, it’s not that.

But the most delicious aspect of this fourth article is that two of its authors, including its lead author, are members of a fringe medical group known as The International Network of Cholesterol Skeptics (THINCS), whose stated mission is to “oppose” the notion that high cholesterol and animal fat play a role in cardiovascular disease. Members of THINCS also take an extraordinarily strong position opposing statins for any clinical use whatsoever. (One might actually assume that, since JUPITER shows that cardiovascular outcomes can be improved by statins in people with normal cholesterol levels, the THINCS would embrace the study as evidence that perhaps cholesterol is not as important as it’s cracked up to be. But apparently, this argument is completely negated by the fact that statins were the vehicle for making it. Many in the anti-statin crowd would object to statins even if they were proven to cure heart disease, cancer, baldness, and obesity AND produced fine and durable erections upon demand.)

The best part of all this is that the astounding anti-cholesterol, anti-statin bias of the authors was not disclosed in their article – whose main thrust, again, was to criticize the disclosed biases of the JUPITER investigators.

The excellent Pharmalot blog noted this irony, and contacted Rita Redberg (editor of the Archives) and Michel de Lorgeril (THINCS-master and prime author of the fourth article) to ask them why the association with THINCS was not disclosed.

Redberg:

“I’m not clear this is an undisclosed conflict. The policy mentions a personal relationship that could influence one’s work. I think that could be a big stretch. My initial impression is the group has an intellectual message, but doesn’t fit as a personal relationship that could effect the authors’ work.”

de Lorgeril:

“[While it is] very important to disclose financial [emphasis DrRich's] conflicts of interest that can influence our way of working and thinking about cholesterol and statins, there is so far no obligation to provide a CV each time we publish any thing…May I underline the fact that being a member of THINCS – not a group of terrorists, mainly a club of very kind retired scientists with whom I have interesting and open discussion – is not a conflict of interest?”

DrRich may be old fashioned, but he thinks that being a member of an “out there” group like THINCS, which appears to advance selected and distorted data on its website aimed at furthering its stated mission of “opposing” (not investigating or questioning) the cholesterol hypothesis and the use of statins, might make one prone to a bit of bias when writing a broadside critiquing a study like JUPITER, and loudly criticizing anyone associated with that study for their bias. This sort of bias (demonstrably rooted in a willingness to select/ignore/distort data in order to make a preconceived point) is likely to be as strong as any that might accompany, for instance, receiving a stipend from a statin company for participating in clinical research. Membership in THINCS may not preclude one from writing such an article, but DrRich thinks the association at least ought to be disclosed, just as financial relationships must be disclosed.

DrRich has a hard time explaining how this can happen with a prestigious medical journal like the Archives. But like Sherlock Holmes says, when you have eliminated the impossible (such as, the idea that this article deserved to be published in its current form), whatever remains, however improbable, must be the truth.

And this is why DrRich can only conclude that several of the authors appearing in this week’s issue of the Archives of Internal Medicine, along with its editor, are in the mode of ingratiating themselves to the sundry officials and czars within the Obama administration who will be assembling the expert medical panels, those panels which will be making the momentous decisions that will determine the flow of hundreds of billions of dollars, and (forgive me) of life and death.

We wish them the best of luck in their audition, and will be monitoring the memberships of the new panels with interest, to see if any of our new friends are ultimately successful.

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DrRich critiques more arguments for withholding Crestor here.

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_Sources:

_{de Lorgeril M, Salen P, Abramson J, et al. Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy. A critical reappraisal. Arch Intern Med. 2010; 170:1032-1036.}

_{Kaul S, Morrissey RP, Diamond GA. By Jove! What is a clinician to make of JUPITER? Arch Intern Med. 2010; 170:1073-1077.}

_{Ray KK, Seshasai SRK, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention. A meta-analysis of 11 randomized controlled trials involving 65 229 participants. Arch Intern Med. 2010; 170:1024-1031.}

_{Green L A. Cholesterol-lowering therapy for primary prevention. Still much we don’t know. Arch Intern Med. 2010; 170:1007-1008.}

________________________________

Now, read the whole story.

DrRich explains it all in, Fixing American Healthcare – Wonkonians, Gekkonians and the Grand Unification Theory of Healthcare.

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 Physician-Industry Relationships – What Is Appropriate? [21:13m]: Play Now | Play in Popup | Download (185)

The following is a close approximation of a talk DrRich gave to a gathering of some of the world’s most promising young cardiac electrophysiologists, in Nice, France, on June 15, 2010. He was asked to talk to these young physicians about physician-industry relationships. The organizers of this gathering apparently did not know, as anyone who reads this blog would know, that DrRich should never, ever be allowed an opportunity to influence promising young physicians.  But, what’s done is done.

* * * * * * * *
A worldwide controversy is now roiling over the appropriate relationship between physicians and industry. Superficially at least, this controversy has to do with the undisputed fact that a physician’s relationship with industry can unduly influence his or her behavior.

That is, this controversy is said to be related to the conflicts of interest (COI) that are always inherent, to some degree, in such relationships.

I believe there is a deeper, and far more disturbing, reason behind this controversy, and I will address it in a short while.  But let’s first talk about COI, because it is ostensibly the chief concern, and it is in fact a very important issue.

A COI is present when an individual has a sacred, fiduciary duty (i.e., a duty of trust) to Entity A, but then develops a secondary relationship with Entity B, which (by creating self-interest, competing loyalties, or even just an inability to be objective), threatens to interfere with the primary duty to Entity A.

Physicians, especially academic physicians, have (at various times) at least three primary fiduciary duties that must take priority. These are: a duty to patients when practicing medicine; a duty to students (i.e., actual students, colleagues, or the public) when teaching; and a duty to society (and truth itself) when conducting medical research.  It is clear that ties with specific companies and their products can easily create important COI that may interfere with each of these primary fiduciary duties, and it is equally clear that physicians have commonly allowed this interference to happen.

Far more often than we like to imagine, doctors have allowed bias to creep in when recommending a course of action for their patients, in imparting knowledge to trainees, colleagues or the public, or when designing, analyzing or reporting results of clinical trials. And typically, most doctors who exercise inappropriate bias have convinced themselves that they are really acting in the best interests of their patients, students or society at large. For it is quite difficult to be objective about one’s own COI.

And there is no question that industry has become adept at the gentle art of creating COI among physicians (subliminally whenever possible), and have carefully incorporated the creation of such conflicts into their business models.

Obvious abuses we have all seen include doctors “shilling” for companies or their products at national meetings; clinical guidelines committees seeded with biased members; unbelievable amounts of money (well above “fair market value) being paid to key doctors for consulting services; long advertisements disguised as CME events; and ghost-writing scientific papers, then recruiting prominent physicians to sign on as “authors” after the fact. There are many others.

Such ongoing abuses of our fiduciary duties ought to be deeply embarrassing to us in the medical profession.

And if it’s not embarrassing, it is at least becoming painful. In the US, physicians who are discovered doing some of these things are being called out publicly, being investigated by Congress if not the Justice Department, losing their prestigious academic positions, and having their reputations destroyed. It is hard to be sympathetic toward them.

Despite all the negative attention – both public and legal – that such COI have brought to our profession in recent years, many of us continue to have tin ears.  A recent example, which has caused a stir in the blogosphere if nowhere else, happens to relate to the EP community. (Thanks to Larry Huston of Cardiobrief who did the heavy lifting on this one. )

Recently, the ACC/HRS collaborated in the launch of a new website, called AFibProfessional.org, which is described as “a unique collaboration to address atrial fibrillation for the cardiology community.” The site has only one corporate sponsor – Sanofi, the maker of Multaq.

At the time of launch, all the content on this new website consisted merely of old, recycled material from older ACC and HRS websites, with a single exception. The single exception was a slide lecture by a prominent electrophysiologist, who we all know and love, on “Managing Atrial Fibrillation.”  This lecture makes a strong case for the off-label, off-guideline use of Multaq. The lecture was posted without any COI disclosure statements, though the lecturer, it turns out, has significant financial ties to Sanofi.  When the matter became a public issue, the lecture was pulled from the site, and the ACC promised to investigate. A few days later, the investigation apparently completed to the ACC’s satisfaction, the lecture was reposted, this time with a COI disclosure.

While one hesitates to suggest malfeasance here, it certainly looks bad.  For the ACC and HRS to co-sponsor a brand new website that , by all appearances, is chiefly a vehicle for advertising Multaq suggests, if nothing else, that we in the medical profession, and our professional organizations, still don’t get it. If we don’t police our own COI, it will be policed for us.

What remedy should be applied?  A reasonable approach would be to recognize that physician-industry ties will always bring at least some COI, and to manage the problem by strictly limiting inappropriate COI, and fully disclosing any that remain.

Accordingly, a number of groups – most prominently the Institute Of Medicine – have recently made formal, and tough, recommendations regarding physician-industry relationships. The final “rules” under which we will all have to live are still being negotiated.

But it is highly likely that they will include many if not all of the following:

-    Doctors should not accept any gifts, no matter how small, from industry. These include trivialities such as pens and notepads, and more substantial gifts such as meals and travel.
-    Doctors should not give presentations in which content is controlled or influenced by industry.
-    Doctors should not consult for industry without a written contract, nor should they receive more than “fair market value” for consulting activities.
-    Doctors should not accept drug samples from industry.
-    Doctors who have a financial interest in a product or company should not participate in clinical trials in any capacity that involve that product or company, including patient enrollment, data collection, analysis or reporting.
-    Doctors who have industry ties should not participate in the development of clinical guidelines.
-    Medical schools and professional organizations should not accept direct funding, or attributable funding, for CME.
-    Any interaction with industry will be fully disclosed, and made publicly available.

What this “full disclosure” will look like can be seen in the Physician Payment Sunshine Act, a law which is pending in the US. Under this act,  all “transfers of value” totaling $100 or more in a year to any physician will be reported by each company to the government annually, along with each physician’s identifying information. Such “TOV” includes food, trinkets, entertainment or gifts; travel; consulting fees or honoraria; funding for research or education; stocks or stock options; ownership or investment interest, and any other economic benefit.  This information will be posted on a public, searchable government website. Companies will be fined $10,000 for each incident of an unreported TOV.

You younger physicians will be spending your careers in a COI environment that is significantly different from that which we, your elders, have experienced. Activities that have been acceptable, and even encouraged, will now cause you to be publicly stigmatized, or worse. This matter is in great flux, and you need to pay close attention to it as the rules are changing. In the meantime, you need to choose your interactions with industry very carefully, and very circumspectly.

Everything I have just discussed assumes that the real issue regarding doctor-industry relationships is COI. Indeed, everything I have discussed assumes a particular way of looking at industry relationships, which I will call Theory A. Theory A, goes as follows:

Theory A:

-  Medical progress is Good, and benefits mankind.
-  Industry is responsible for a high proportion of medical progress.
-  Industry-driven progress requires the active participation of physicians.
-  Therefore, a well-managed cooperation between industry and physicians is beneficial to mankind, and ought to be encouraged.

If you subscribe to Theory A you believe that, because well-managed physician-industry relationships benefit mankind, these relationships are good. So, fundamentally, it’s the management of these relationships which is at issue. These beneficial relationships produce unavoidable COI, which we must manage by strictly limiting their extent, and fully disclosing the ones that are left.

On the surface, at least, that’s what the debate is about – where to draw the necessary limits.  But just below the surface, the debate is about something else entirely. Beneath the surface, Theory A is rejected outright.

Today we hear prominent voices telling us that merely managing COI does not go far enough. No amount of COI is acceptable, and ALL physician-industry ties should be prohibited.  Among these is Jerome Kassirer, former editor of the New England Journal of Medicine, who says, “The ideal handling of COI is not to have them at all.” For these voices, Theory A simply does not apply. Rather, (I submit) they subscribe to Theory B:

Theory B:

-    The greed of medical industry creates excessive costs, and produces far more harm to society than good.
-    Physician-industry alliances strengthen industry, and increase the harm.
-    Therefore, crippling these unholy alliances is critical to the interests of society.

A corollary of Theory B is that it can only be the State’s job to cripple these alliances.

Proponents of Theory B, noting, not incorrectly, that medical industry is chiefly concerned with profits rather than the public good, conclude that industry will always behave in ways that are counter to the interests of society.  While many proponents of Theory B will agree that industry provides at least some benefits, they are convinced that these benefits are far outweighed by the harm they produce. Therefore, Theory B proposes to stifle, if not cripple, medical industry. And a very useful strategy for achieving this goal is to de-legitimize any practical relationships whatsoever between medical industry and physicians.

Proponents of Theory B rarely say what their real goal is. Most of them give lip service to Theory A. One must discern their real motives from their behavior.

Much of that behavior, in practical terms, has to do with controlling the flow of information. Let industry develop whatever it wants (perhaps), but don’t let profit-drunk industry – or its greedy physician spokespersons – instruct doctors and patients on who gets to use industry’s products, or when and how.

That kind of information can only be managed by unbiased sources. Proponents of Theory B invariably refer to government-appointed panels of experts to determine which products of industry are good and bad, and to manage the flow of information about them. Information coming from anywhere else is to be regarded as being charged with bias and greed, and should be ignored, or even suppressed.

Inherent in this viewpoint is the notion that the State is an honest broker, with no bias of its own, except to do what is best for the population. The State, in its disinterested beneficence, is the only civil entity which can pass judgment on which medical information is suitable for general consumption.

But even as a general proposition, no government is an unbiased and honest broker. Politics, according to Harold Lasswell, an early Progressive political scientist, is determining who gets what, when and how. Government officials do not cancel their own human nature when they put on a government name tag. As they go about the business of determining who gets what, when and how, they inevitably – and most often intentionally – create various favored constituencies, fiefdoms, and clienteles to suit their own goal. That goal is to consolidate and expand their own authority. In this way, in the exercise of its political mandate the government always creates co-dependencies, and determines winners and losers. So even in the general case, the government cannot be an honest broker.

But with regard to healthcare, government bias goes far beyond the general case. Healthcare spending is the chief problem governments face today. In the US, projected Medicare expenditures over the next 30 – 40 years will be $35-55 trillion. Numbers like this are deeply destabilizing, and simply cannot be abided, and promise nothing but chaos, revolution, and societal disintegration.

To the State, controlling healthcare spending is an existential problem, a matter of life and death, an issue that justifies any solution that has even a slight chance of working.

Why is the cost of healthcare rising so rapidly? Fundamentally, it is medical progress. Medical progress has greatly increased overall healthcare expenditures. Simply consider, for instance, the many fatal illnesses we have converted to chronic, and chronically expensive diseases – coronary artery disease, kidney disease, HIV/AIDS, various forms of cancer, and heart failure, to name a few.  Medical progress has made great strides in early detection and prevention, and preventive medicine always increases the cost of care.  And thanks at least partly to medical progress, life expectancies are on the rise, and people have many more years to consume healthcare.

Medical progress is very expensive, and the more we have of it the more it costs. The State can only look at medical progress and say, “Medical progress is killing us.”

But it is not politically feasible to come right out and say that stifling medical progress is necessary to the survival of the State. Rather, the State must assert that what it is stifling is greed.

Hillary Clinton gave us the State’s operative formulation in 1993: “There are just too many greedy doctors using too much expensive technology.”  So, to control costs, the State must control the doctors; and the State must control the technology, which is to say, industry.

I submit that an underlying theme within the debate over doctor-industry relationships is a desire to greatly slow or even stop the real threat to the State: medical progress, and the vast expenditures which medical progress produces.

The State has several means for stifling medical progress.  The State can institute increasingly oppressive regulations, which can have the effect of hamstringing industry, but more importantly, has the effect of converting industry to a client of the State, dependent on the State’s favors for its success. The State can demonize industry, trying to convince the public that drug companies and medical device companies are evil entities that would just as soon harm them as help them, and indeed, without the strong hand of the State would prefer to distribute pain and suffering as the more favored pathway to windfall profits. But more to the point of today’s discussion, the State can stifle the doctor-industry relationships that are so critical in steering medical progress in a clinically relevant direction.

So the  interests of industry must be represented as being fundamentally counter to the interests of society, and the doctors who have relationships with industry must be painted as their evil (or, at best, deluded) minions.

Yes, industry is biased, and industry will act on that bias whenever they can get away with it. Industry just can’t help itself. That’s just the way it is.

But the State is also biased. And the State will also act on that bias whenever they can get away with it. The State can’t help itself. That’s just the way it is.

Industry will try to exercise its influence over us by data-driven persuasion, and when that fails they will try to sweeten the persuasion, perhaps even with subtle or not-so-subtle bribes.

But the exercise of persuasion is even more dangerous when done by the State. While the State may also try to influence us with data-driven persuasion, it is very quick to resort instead to propaganda (i.e., the art of information-control by which the unwashed masses are told only what the specialized classes have determined is best for them), and when that fails, the State will resort to its ultimate form of persuasion – the enforcement of new and suppressive regulations at the point of a gun.

So, while industry is indeed biased, and needs to be kept at arms length, de-legitimizing industry altogether would be disastrous.  It would create an open field for extraordinarily powerful forces which are at least as biased, but in the opposite direction. If we value medical progress, we need the balance that industry provides – and that includes not only industry’s products, but its voice.

Medical progress driven by industry-physician collaboration is good for mankind. But that collaboration inevitably creates conflicts. We physicians need to control those conflicts, or the collaboration will be forcibly terminated altogether. Our professional history to date is bleak in this regard, and we only have one chance left to get it right, if that.

But in controlling our COI, we should not allow ourselves to be pushed too far. We should agree to reasonable limits on conflicts, and on full disclosure of any conflicts that remain. But we should draw the line when we are urged to forgo all relationships with industry altogether. We must recognize that industry and its selfish goals provide a necessary counterbalance to even more powerful forces whose goal is to stifle medical progress.

I don’t ask that you accept my synthesis of this problem at face value. I simply ask that you listen to what I am suggesting, and observe for yourself what is happening out in the wild. Then challenge yourself to come up with a better explanation for what you see happening out there. I sincerely hope you can, as I would much rather that my conclusions were not true. So if you do come up with a better explanation, I will greatly appreciate hearing about it.

________________________________

Now, read the whole story.

DrRich explains it all in, Fixing American Healthcare – Wonkonians, Gekkonians and the Grand Unification Theory of Healthcare.

Now on Kindle!

Richard N. Fogoros, M.D. (DrRich) is a former professor of medicine and a longtime practitioner, researcher and author in the fields of cardiology and cardiac electrophysiology. He currently makes his living as a consultant in research and development with biomedical companies, and as a writer.

In addition to all the fine prose you’ll find here on the Covert Rationing Blog, you can revel in even more of DrRich’s stuff at the Heart Disease site at About.com (which is a New York Times Company, making DrRich one of the few conservative Americans who wishes the NYT great success), and on the “parent” website of this blog, The Grand Unification Theory of Healthcare.

His award-winning book, Fixing American Healthcare – Wonkonians, Gekkonians and the Grand Unification Theory of Healthcare (Publish or Perish DBS, Pittsburgh, 2007), is quite entertaining (for a policy book), has won lots of accolades – and would still be worth reading if President Obama hadn’t come along and solved all our healthcare difficulties with a flick of his pen.

You can reach DrRich by e-mail here:  drrich at covertrationingblog.com

Podcast:

 

 Neuroscientists Beware! Here Come the Cardiologists! [17:31m]: Play Now | Play in Popup | Download (108)

Throughout the millennia, the characteristic that has distinguished robust barbarians from extinct ones is that, when forces beyond their control begin encroaching on their turf, they simply pick up and encroach on the turf of less aggressive people (generally, of people who are more advanced, both intellectually and culturally, than they are).

And so, when the Feds begin making noises about limiting some of cardiology’s favorite revenue-generating activities, the cardiologists – among the most robust of the medical barbarians – are quick to overrun the turf of other, less bloodthirsty and more civilized, medical specialists.

DrRich in the past has attempted to warn his medical colleagues about the predatory nature of cardiologists. He has told how the cardiologists have driven the formerly proud and powerful cardiothoracic surgeons into a sad state of underemployment, how they have usurped the formerly sovereign territory of diabetes specialists, and how they are currently laying siege to sleep medicine and bariatrics.

And now, continuing his public service to the less robust medical specialists (whose great achievements, like all cardiologists, DrRich admires), he must reluctantly extend his words of warning to his friends, the neuroscientists.

Cardiologists began encroaching on the field of neurology many years ago, but only surreptitiously, when they took to blaming imbalances of the autonomic nervous system (i.e., dysautonomia) on mitral valve prolapse. In more recent years, somewhat more blatantly, they have attempted to take ownership of migraine headaches. And now, just last week, in a full frontal assault, cardiologists laid claim to Alzheimer’s Disease.

Neuroscientists, nobody is safe! Hide your women and children!

The pattern of behavior employed by the invaders is easy enough to spot. First, cardiologists call attention to an alleged association between some cardiac condition (a condition they will manufacture if necessary), and a non-cardiac medical problem. Then, immediately, they will assert that (or at least begin behaving as if) the association proves a cause-and-effect relationship. Finally, since they have “proven” that the non-cardiac medical problem is caused by a cardiac condition, patients who have (or might develop) that non-cardiac medical problem need to be referred to cardiologists, who, lo and behold, have invented a well-paying procedure to treat it, or at least, to study it further.

The best known example is mitral valve prolapse (MVP), a congenital condition in which the mitral valve partially flops open when it should be closed, thus allowing blood to flow backwards (i.e., to regurgitate) across the mitral valve as the heart contracts. (For anyone interested, here’s a brief description of the heart’s chambers and valves.) Now, significant MVP can be a serious medical problem, and it often requires mitral valve surgery. Fortunately, however, significant MVP is a relatively uncommon condition.

The problem is that echocardiography (a non-invasive test using sound waves to create an image of the beating heart) has become so advanced that some degree of trivial MVP, it seems, can be found in almost anybody. According to some studies, as many as 25 – 35% of healthy individuals – people without any cardiac problems or any symptoms whatsoever – can be said to have some degree of MVP. In fact, whether you have MVP or not depends largely on what criteria the echocardiographer uses to make the call, and how badly the doctor wants you to have the diagnosis.

Over the years it has become customary to diagnose MVP in young, apparently normal people who have the temerity to complain about the highly disruptive symptoms of dysautonomia (such as fatigue, weakness, strange pains, dizziness, constipation, diarrhea, cramps or passing out), without supplying the kinds of objective physical or laboratory findings which, doctors insist, patients are always obligated to provide. Such thoughtless patients are now routinely sent for echocardiography, so that MVP can be diagnosed (since it can be diagnosed just about whenever it is looked for). The patient is then given the diagnosis of “mitral prolapse syndrome,” even though: a) the MVP is usually so trivial as to be nonexistent; b) the studies which claim to show an association between MVP and these sorts of symptoms are generally based on a gross over-diagnosis of MVP; and c) there is no credible theory based on actual physiology to explain how MVP – even real MVP, much less the trivial kind – might cause such symptoms.

But no matter. “Rule out MVP” has become one of the most common reasons for young, healthy people to be referred for echocardiography, and has become a staple source of income for cardiologists.

The story is similar for the association between patent foramen ovale (PFO) and migraine headaches. In the developing fetus, the foramen ovale is a hole that is present in the atrial septum (the thin structure that separates the right atrium from the left atrium). At birth, a flap of tissue imposes itself over the foramen ovale, causing it to close. In some people, however – people with PFO – the tissue flap is still capable of flopping open. In people with PFO, the foramen ovale can open transiently if the pressure in the right atrium becomes transiently greater than the pressure in the left atrium, such as with coughing, or straining during a bowel movement.

In rare instances, strokes in healthy young patients have been attributed to PFO. The supporting theory is that a stroke can occur when a blood clot happens to be coursing through the right atrium at the precise moment a person with PFO is coughing (for instance), allowing the clot to move into the left atrium, and on to the brain. And because this theory is at least plausible, in a young person who has an unexplained stroke and is then found to have a PFO, it makes at least some sense to close the PFO.

But the presence or absence of a PFO is a little like the presence or absence of MVP. Its diagnosis depends on how hard the echocardiographer looks for it, and on how much the doctor would appreciate the diagnosis. With modern echocardiographic equipment, at least some sign of PFO can be found in as many as 25% of normal individuals.

Being able to make this nifty diagnosis is of little use to cardiologists if the only clinical problem it may cause is a one-in-a-million chance of stroke. One cannot make a living, or even make a car payment, doing echocardiograms in young patients with cryptic strokes. They’re just too darned rare. So it didn’t take long for cardiologists to draw a more useful association – this time, between PFOs and migraine headaches.

While all the things that have to happen in order for a PFO to cause a stroke are very unlikely, it is at least possible that they could all occur simultaneously in a patient. This is not the case with migraine. No plausible theory has been advanced to explain how PFO might cause migraines. The only reason PFO is being invoked as a cause for migraine is that when patients with migraine have been carefully studied for the presence of PFO, an increased incidence of PFO was found. But (as we have seen) when PFO is carefully sought in any population of patients, it is more likely to be found. The only likely reason PFO has not been associated with cancer, red hair, type A personality, or difficulty in memorizing the multiplication tables is that cardiologists have not thought of looking for it (yet) in these conditions.

For cardiologists, the poorly-supported allegation that PFO causes migraine is particularly compelling, since not only can they get paid to look for PFOs in migraine sufferers, but also there is an invasive (and lucrative) procedure they can do to close PFOs, to “treat” the migraines. Studies to date have not been successful in showing that closing PFOs improves migraine headaches, but that hasn’t kept cardiologists from screening migraine patients for PFO, then offering them PFO closure as a therapeutic option.  This, again, is because an association implies cause and effect, at least when that implication can be helpful to someone.

Migraine sufferers are particularly vulnerable to this and many other unproven therapies, since they are often disabled by their condition, and in many cases medical science (or medical ignorance) offers them insufficient help. Consequently, anecdotal stories abound regarding unorthodox therapies that cure migraines. DrRich, himself a migraine sufferer for many decades, has heard all the stories. (He even has one of his own. If DrRich maintains a schedule of running at least 20 – 25 miles a week, he does not get migraines. If he quits running for a few weeks the headaches come roaring back. He has mentioned this decades-long and reproducible pattern to several neurologists and other specialists over the years. They conclude that DrRich – and this should not be a surprise to many of his readers – is nuts. But if cardiologists had a billable procedure that could make you exercise, you can bet they’d fold DrRich’s experience into their formal clinical guidelines.) In any case, merely performing PFO closures on a few migraine suffers was almost guaranteed to produce a patient here or there who would report a positive response. And despite the continued negativity of actual clinical trials so far, that’s what happened.

So, at least by anecdote if not by controlled trial, closing PFOs can cure migraines.

But now it gets even worse for the neuroscientists. Any neurologists who ignored the cardiologist’s usurpation of dysautonomia, and who may have felt only a little more concern when cardiologists began to lay claim to migraine headaches, had best sit up and take notice. Because now, cardiologists have a way of treating (at least preventing, if not actually curing) Alzheimer’s Disease.

This time it is DrRich’s own particular sub-branch of the cardiology tribe which is the culprit – the electrophysiologists.  In a way, it is a little disappointing for DrRich to see his EP brethren going in for the same, turf-grabbing sophistry used by lesser cardiologists. EPs are known for being more intellectually sophisticated than your typical heart doctor (who, after all, is a glorified plumber). Indeed (as he thinks he may have mentioned in the past), DrRich has a neurosurgeon friend who, when he wants to convey the idea that what he is doing isn’t quite as difficult as it appears, but at the same time what he is doing is, in fact, neurosurgery, will say, “It’s not exactly electrophysiology!” But of course, he may not say this anymore once he finds out what we EPs are up to.

Last week, at the Heart Rhythm Society Scientific Sessions, researchers presented a study suggesting that ablation procedures for atrial fibrillation are associated with a lower risk of Alzheimer’s disease. (Here’s some information on atrial fibrillation and its treatment for anyone who is interested.) The study was presented as an abstract only, so we know relatively little about the specifics.

But, really. Atrial fibrillation and Alzheimer’s are both disorders associated with aging, so it is not surprising that they are associated with each other – in the same way that atrial fibrillation is associated with gray hair, cataracts, and bunions. Ablation for atrial fibrillation is a relatively lengthy and difficult procedure, whose results are relatively middling, and which carries a substantial risk of some really nasty complications. So these ablation procedures are generally reserved for carefully selected, reasonably ideal candidates – usually, the relatively young, relatively healthy atrial fibrillation patients, who are less likely to get Alzheimer’s disease over the next few years whether they have ablations or not.

So there is a lot to be cautious about in interpreting a preliminary study like this one. For a well-presented, comprehensive treatment of why the results of this study should be largely ignored for now, see Dr. John M’s blog. (It sounds like John M is as embarrassed by his fellow EPs in this instance as is DrRich).

But such objections as DrRich and John M may express are just quibbles. The headlines are already blaring: “Ablation Procedures For Atrial Fibrillation Prevents Alzheimer’s.” Whatever the details and limitations of this study, cardiologists can now treat Alzheimer’s. Mission accomplished.

Having duly (and humanely) called this problem to the attention of his neuroscience friends, DrRich would like to finish by emphasizing a larger point.

You can’t fight the Feds. When the sovereign authority, at the point of a gun, decides to reach down into the world of the medical specialists, and dictate which medical services are no longer going to be feasible (all for the noblest of purposes, of course – to maximize quality and efficiency and the collective good), the affected medical specialists have a limited range of possible responses. And fighting the Feds is NOT among these available responses.  Better to fight the change of seasons.

So the affected specialists can contract their horizons, take what’s left, and try to make the best of it. Or, they can do what the Visigoths did when the people of the steppes displaced them. Strike out against other, weaker specialists, and take what’s theirs. If you can’t grow the pie anymore, then take the other guy’s piece.

DrRich is not passing any judgment on his cardiology brethren here. He is just describing what’s happening, as a public service. You neuro-types, he believes, have a right to be told what’s happening. You can do with the information as you see fit.

In the meantime, DrRich remains supremely confident that his cardiology colleagues can find a nearly unlimited supply of plunder in this brave new world. They are very robust barbarians.

Sure, nobody’s read the bill, and even if they had, what Nancy said is true: To find out what’s in the bill, they first had to pass it (so the bureaucrats could translate it into the hundreds of thousands of regulations that would finally determine its meaning). But there’s no need to wait for the regulators to sort it all out. DrRich can tell you what you need to know about our new healthcare system right now!

Healthcare Reform Explained – An Updated Guide For The Perplexed

PCP’s: Here’s All You Need To Know About Our New Healthcare System

Why the Health Insurers Saved the Day

The Individual Mandate Will Stand

The Audacity of Perpetuity

Some Powers of the Immutables

Podcast:

 

 Breaking the Doctor-Patient Relationship (Limiting Individual Prerogatives, Part 3) [20:54m]: Play Now | Play in Popup | Download (14)

____________

Part 1 of Limiting Individual Prerogatives

Part 2 of Limiting Individual Prerogatives

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The thing about Progressives is that the characteristic which makes them most endearing (and, which makes them most attractive to the unaware), is the very characteristic which makes them the most dangerous.

Fundamentally, Progressives believe in the perfectibility of mankind, or at least, of society. Indeed, they have discovered the very Program which will lead to the perfect society, a society which will maximize the good of the whole. Their vision is so compelling, and their ends so utterly and undeniably right, that it becomes legitimate for them to engage in whatever means are necessary to achieve it. (Indeed, for those who have been paying attention, “By Whatever Means Necessary” appears to have supplanted “Hope and Change” as the catchphrase of our current political leaders.)

The thing that always trips up Progressives (and their more revolutionary cousins, the Communists), is, of course, human nature. In order for their Program to work, it is necessary for each individual to behave in the prescribed fashion. And, at the end of the day, a substantial proportion of the population (any population) will insist on striving for their own individual benefit, rather than (as the Program requires) for the benefit of the collective.

The major competing system of societal organization – capitalism – recognizes this facet of human nature (i.e., the essential imperfectability of mankind, as manifested by the non-suppressibility of self-interest), and attempts to channel it into relatively productive and non-destructive (but still competitive and individually-directed) behaviors that limit the damage, and maximize the public good to a reasonable degree.

In contrast, Progressives attempt to change human nature to fit their inherently superior Program.

The fact that you cannot change human nature to fit the Program is what makes them dangerous. Their initial wide-eyed optimism that us folks will just “get it,” once they explain it to us, invariably evolves to an essential contempt for our limited intellectual capacity. This contempt justifies all manner of prevarications, to fool us into going along. Even in societies where the tyranny of correct-thinking has gone so far as to elicit the cooperation of the people at the point of a gun (rather than through the preferred methods of “education” or misdirection), the achievement of the predicted perfect society is invariably prevented by the recalcitrance of human nature. (The final realization that not even an all-powerful central authority can make people behave in the prescribed way always produces a nearly psychotic frustration that – in virtually every Communist country – has led to atrocities against various subsets of the recalcitrant people.)

DrRich does not believe there will ever be pogroms in the United States.

But this does not mean that the Progressives will always be kind and gentle as they attempt to achieve their goals. As DrRich sees it, in the U.S. the Progressives have clearly evolved to the “contempt for the masses” phase of their Program, a phase which justifies all manner of techniques – just this side of violence – to get us all to cooperate. Currently they are intent on demonizing their opponents as being racist, stupid, uneducated, selfish, overly dependent on outmoded supernatural beings, violent, and (of course) obese. This demonization is quite useful, since there is obviously no need to address any actual ideas put forth by such as these, even if they were capable of the feat of “ideas.”

Healthcare is, at present, the chief battleground in the war between Progressives vs. non-Progressives in the U.S., and the outcome of this battle will likely determine the success or failure of the entire Progressive Program. And the most fundamental (and emblematic) aspect of this battle is over what to do about the “doctor-patient relationship.”

The classic doctor-patient relationship was a celebration of the primacy of individual rights. And, for over 2000 years (at least since the advent of the Hippocratic Oath) guaranteeing the sanctity of that relationship was the basis of all medical ethics.

Until very recently doctors, patients, philosophers and ethicists recognized that, when you are sick, you are no more capable of navigating a complex and hostile healthcare system than are accused felons a complex and hostile legal system, and you are no less in peril if you run afoul of that system. And, just as the felon has a right to a personal advocate, a professional whose job is to protect his individual interests against the conflicting aims of the “system,” so does the patient. That is (quaint conventional wisdom held), when you are sick, you should be entitled to at least the same protections as when you rob a convenience store. And the doctor-patient relationship was supposed to guarantee you that right.

This is why, throughout the ages, the basic precepts of medical ethics were aimed at guaranteeing the sanctity of the doctor-patient relationship. Fundamentally, these ethical precepts required the physician to place the needs of his or her individual patient above all other considerations.

It should be clear to everyone that, under either our “old” healthcare system or the one that Obamacare promises us, this formulation of the doctor-patient relationship cannot be allowed to stand. Neither the insurance executives nor government officials can allow spending decisions – that is, decisions on how to spend their money – to be made by individual patients (and their personal advocates). For this reason, the classic doctor-patient relationship had to go.

And so, in 2002, official medical ethics was formally amended to require physicians (while still giving lip service to their obligation to individual patients) to strive for a “just distribution of healthcare resources.” That is, official medical ethics now makes it ethical for physicians to ration healthcare, covertly, at the bedside – and indeed, makes it unethical for them to fail to do so.

The New Ethics has been enthusiastically supported by medical ethicists worldwide (a field which now seems to be dominated by utilitarians), and worse, has been embraced by all the world’s major medical professional organizations. DrRich has not embraced the New Ethics (on the grounds that it places individual patients at great peril, and destroys the profession of medicine), and neither have many (possibly a majority) of older physicians. But it has been taught in medical schools around the world for over a decade, and in another decade it is likely that the vast majority of practicing physicians will accept as a matter of course that their primary obligation is to control healthcare costs, and only secondarily to try to meet the needs of their individual patients.

The plan, therefore, is for Obamacare to provide physicians with directives from expert panels on which medical services to supply to which patients and when, and for the New Ethics to allow physicians who go along with such directives to live with themselves. The feasibility of this plan depends entirely on physicians acceding to the program.

So, incentives are being put in place to “help” doctors cooperate. Quality measures will be implemented, with “quality” being defined as doctors doing what they’re told, and reimbursement will be tied to one’s quality rating. Possibly more persuasive will be the fact that the Feds can construe the failure to follow handed-down rules, regulations and guidelines, at any time, as a federal crime. (Even doctors who don’t mind being labeled as “substandard quality” – perhaps even considering the label as a badge of honor – will mind going to jail.)

But by whatever means necessary, the happiness of the government is to be the doctor’s first consideration, and not the happiness of their individual patients. The classic doctor-patient relationship is being terminated with extreme prejudice.

To see just how important it is to destroy the doctor-patient relationship, one merely has to observe what is happening to primary care doctors who have the audacity to leave the system, and set up a direct-pay medical practice.

Part of the problem, to be sure, was caused by these doctors themselves. The first few to do so unabashedly catered to rich patients, and to attract the rich, referred to themselves as “concierge” practitioners. This name (and its elitist connotations) have been forcibly affixed to all direct-pay practitioners, even as this style of practice has evolved into a much more democratic form. Today, more and more doctors are starting direct-pay practices (in which patients pay the doctors out of their own pockets) which are easily affordable to anyone who can afford a cell phone or cable TV contract.

While many direct-pay practices offer patients certain benefits they can usually not get from primary care doctors who remain in the approved system (such as phone and e-mail access, same-day appointments, appointments lasting as long as necessary instead of the allotted 7.5 minutes, etc.), the fundamental benefit, to both the patient and the doctor, is that it restores the classic doctor-patient relationship. The physician’s primary obligation is no longer to the 3rd-party overlord, or to the Progressive ideal of social justice, but to the patient.

And while critics (who abound) attack direct-pay practitioners for their elitism, laziness, and greed, their real issue is that direct-pay practitioners are acting as if their primary duty is to their individual patients, and not to the needs of society. This latter fault simply cannot be tolerated.

Having gained nearly complete control over the behavior of primary care practitioners, it is critical for Progressives – in making sure that practice by handed-down “guidelines” is not simply the only legal way to practice, but also the only ethical way to practice – to shut the door to any alternative forms of primary care. Direct-pay practitioners are a menace because they threaten to raise the expectations of both doctors and patients. Perhaps, doctors and patients might tell themselves, there really is a way to maintain individual autonomy within the healthcare system.

The attacks on direct-pay practitioners have followed the usual scheme Progressives follow when they discover a faction they need to suppress. First, they were ridiculed. “For a Retainer, Lavish Care by ‘Boutique Doctors,’” said a headline in the New York Times in 2005. Then, they were demonized, widely attacked for their elitism, laziness, greed, and lack of fundamental medical ethics. In this latter effort, it was not difficult to find fellow physicians – generally, from the medical organizations which promulgated the New Ethics – to lead the attacks. There are countless examples. DrRich will give just two.

Anthony DeMaria, then President of the American College of Cardiology, criticized the practice of direct-pay medicine in an article in the JACC in 2005, saying, “Personally, I do not mind if people acquire yachts or personal trainers if they have enough money, nor would I object if they secured a physician at their beck and call. However, unlike yachts, health care is not discretionary, and everyone should be entitled to the same quality.” As a matter of social justice, direct-pay physicians improve healthcare quality for only some patients, and so have no place in the healthcare system.

In an article in the New England Journal of Medicine, Troyen A. Brennan (M.D., J.D., and M.P.H., so we know we’re in trouble) really gets to the point. Referring to direct-pay practices as “luxury primary care,” he notes that “traditional medical ethics is rather poorly equipped to address issues related to luxury primary care.” That is, while “traditional” medical ethics always places the individual patient first, that kind of thinking is now outmoded. “(M)ost ethicists now agree that the financial structure of health care is an important subject for ethical consideration. Access to health care, in particular, is a salient ethical issue.” Direct-pay practitioners threaten (by their elitism and the limited size of their practices), to limit access to primary care, and thus are in fundamental violation of medical ethics.

The argument here, for those who missed it (advanced by fellow physicians no less), is that, of the two competing ethical precepts now established by New Medical Ethics (i.e., the physician’s obligation to the individual patient vs. the physician’s obligation to society), clear primacy is to be given to the physician’s obligation to society. Physicians must (like it or not) participate in covert bedside healthcare rationing. Physicians who take the only path remaining to them that allows them to make the individual patient their primary obligation are to be castigated as ethically deficient.

When ridicule and demonization fail to suppress their opposition, Progressive dogma indicates it’s time to resort to force. The first pass in this regard, of course, is always to render the opposition illegal. (Actual violence is reserved for criminals who persist in their misbehavior, despite more polite efforts to get them to behave lawfully.)

Making direct-pay medical practice illegal has not been accomplished yet, but clear efforts have been made in this regard. Noting with alarm the rise of direct-pay primary care, numerous Congresspersons have issued statements of concern, suggesting that perhaps Congress should look into the propriety of such activities.

Indeed, the first step by Congress has already been taken. In 2003, as part of the Medicare Prescription Drug, Improvement, and Modernization Act, Congress directed the GAO to study and report on the effect of direct-pay practices on Medicare patients. The GAO did so in 2005, and a fair paraphrase of its report is as follows: “The practice of direct-pay medicine is not currently a threat to Medicare patients, because the direct-pay movement is not large enough yet to have an impact. If it does begin to have an impact on Medicare patients, action will have to be taken.” That is, direct-pay medicine was considered OK in 2005 not because it was inherently an ethical and legal form of medical practice, but simply because there were not enough practitioners at that time to significantly affect Medicare patients. The clear implication is that Congress stands ready to pass laws outlawing – or, at least, severely limiting – direct-pay practices, as soon as those practices begin to “impact” the system.

Certain state governments are not waiting for Congress to ban direct-pay practices. The state of Maryland (and a few others) have taken the creative position that, because many direct-pay practices work on a retainer basis, they meet the definition of a health insurance company. And as a health insurance company, to be considered legal entities, they have to have millions of dollars set aside to pay for unforeseen “claims.” (Interestingly, this same argument was not applied to Maryland lawyers, who also often work on a retainer model.) According to the Baltimore Sun, the state’s stance in this regard has already successfully caused several primary care physicians to abandon their plans to become retainer practitioners.

Less devious (but more draconian) than the state of Maryland is the state of Massachusetts (whose universal healthcare system, we’ve all heard, is a preview of Obamacare circa 2015). A bill is under consideration in the Massachusetts Senate (Bill 2170) which requires doctors, as a condition of their licensure, to accept payment rates as determined by the government. If it passes, it will be the first actual legislation in the U.S. to ban direct-pay medicine, if only by making it completely impracticable. (Thanks to Dr. Wes for pointing out this important development.)

Since medical licensing is controlled by the various states, of course, it would take 50 bills like the one in Massachusetts to really get rid of direct-pay healthcare. But there are other ways for the Feds to accomplish the same thing. Now that the federal government directly controls all student loans, for instance, it would be a simple matter to make those loans contingent on agreeing to become primary care doctors working strictly within the government controlled system, or to offer loan forgiveness for doctors who agree to do so, or to rescind favorable re-payment conditions (retroactively, and decades after the fact, if necessary) for doctors who go to a direct-pay model later in life.

DrRich does not really know how the Progressives will actually place the final nail in the coffin of the doctor-patient relationship. All he knows is that they have – well, more than the desire – the deep and abiding need to kill that relationship, once and for all. Unless we the people decide we ought to stop them, this is going to happen.

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Part 4 of Limiting Individual Prerogatives

As has been pointed out (pointedly) to DrRich, we do not have death panels in the United States. And indeed, considering that we’re not conducting military tribunals for Islamist terrorists who have tried (or succeeded in) killing and maiming as many of us as possible, it seems relatively unlikely that we’d assemble death panels (which sound even less due-process-friendly than military tribunals) for American patients.

What we will have, however, is a federally-mandated assembly, body, committee, commission, board, diet, parliament, or posse (but not a panel) of experts which will carefully evaluate all the objective clinical evidence regarding a particular medical treatment, and make “recommendations” to doctors about whether or when to use that treatment. The model which frequently has been offered up for our consideration, as we contemplate the workings of such a non-death-panel, is the British National Institute for Clinical Excellence, or NICE.

This being the case, it might be instructive to examine the preliminary decision made by NICE last week to disallow the use of the new antiarrhythmic drug, dronedarone (Multaq, Sanofi-Aventis) for British patients with atrial fibrillation (AF). Dronedarone is a long-awaited drug, painfully developed and tested over a very long period of time, as a potential replacement for the drug amiodarone (which, despite its many drawbacks, is the most commonly prescribed antiarrhythmic drug for AF).

AF is a common heart rhythm disturbance in the elderly and in patients with underlying heart disease. It can cause palpitations, dizziness, poor exercise tolerance and – because blood clots tend to form in fibrillating atria – often leads to stroke. Unfortunately, the antiarrhythmic drugs that are used to treat AF are either incompletely effective, or have potentially dangerous side effects, or both.

Indeed, as a group, antiarrhythmic drugs tend to be only moderately effective, and are toxic and poorly tolerated. Worse, one of the very nasty side effects sported by most antiarrhythmic drugs is the propensity to produce (paradoxically), sudden death from cardiac arrhythmias – a phenomenon we electrophysiologists like to call “proarrhythmia,” since this seems a less unnerving term than “sudden death.”

The reason amiodarone has become the most commonly used antiarrhythmic drug for AF is that it is measurably more effective than any of the other drugs, and better yet, tends not to cause proarrhythmia.

However, if Satan had wanted to invent an antiarrhythmic drug, he would have invented amiodarone. There are at least three features of amiodarone that render it diabolical.

First, as mentioned, the drug is obviously far more effective than other antiarrhythmic drugs, and does not cause proarrhythmia. So on its face, like most entrapping vices, it spins a certain appeal, one that lures doctors into using it far more blithely than they should.

Second, amiodarone has bizarre pharmacokinetics. Before it becomes fully effective, amiodarone needs to completely saturate the tissues of the body. During this “loading period,” which is generally several weeks in duration, large doses are typically used. Once the drug is deemed to be loaded, a relatively small daily maintenance dose can be used. This is because amiodarone is not excreted from the body like most drugs are, by the kidneys or the liver. Instead, amiodarone likes to stay in the cells “forever,” and for practical purposes you get rid of it only through the normal shedding of your body’s cells, such as skin cells and gut cells. This means that once you are loaded with the stuff, it’s a part of you for a long, long time – just about forever. (Amiodarone can still be detected in the blood for at least a year after the last dose.) Once you are on amiodarone, you’re on it.

And third, amiodarone has a unique and disturbing toxicity profile. Because it is stored in essentially every organ of the body, its side effects can affect almost any organ. And because amiodarone continues accumulating in your body as long as you continue taking it, the side effects can develop weeks, months, or even years after you begin the stuff. The side effects of amiodarone are almost too numerous to describe, but some of the more unique ones include:

• Amiodarone commonly causes deposits to form on the cornea – often leading to “halo-vision,” where looking at bright lights at night is like looking at the moon on a foggy evening.
• Amiodarone can cause a very striking and quite disfiguring blue-grey discoloration of the skin, generally in parts of the body exposed to the sun, producing an appearance which has been unkindly termed “Smurf syndrome.”
• Amiodarone often greatly sensitizes the skin to sunlight, so that even trivial exposure can cause a nasty sunburn.
• Amiodarone often causes thyroid disorders, both hypothyroidism (low thyroid) and hyperthyroidism (high thyroid). These thyroid problems are common with amiodarone, can be unusually difficult to recognize and treat, and are often disabling and even dangerous.
• Amiodarone can cause neuropathy of the peripheral nerves, and more disturbingly, significant ataxia (a severe gait disturbance and loss of balance).
• But the most serious side effect of amiodarone is pulmonary toxicity – lung disease. This can take several forms, from an acute respiratory distress syndrome that makes patients desperately ill, requires intensive care, and often results in death, to a more insidious, gradual, unnoticeable, “stiffening” of the lungs that both the doctor and patient can overlook until finally severe and irreversible lung damage is done.

And of course, given the drug’s extremely long excretion period, if any of these side effects should occur (and one or more of them occur in at least 25 – 30% of people who take the drug), you may be living with them (if indeed you remain alive) for quite a while.

As you can see, Beelzebub would be very proud.

When DrRich was a practicing electrophysiologist, his rule was to offer amiodarone only if the arrhythmia being treated was life-threatening or very disabling or disruptive to the patient’s life, and for which there were no other reasonable therapies, and only after a long, long talk about the potential risks. He has always been distressed that many of his cardiology colleagues appear to prescribe it so readily.

In any case it is no wonder that a substitute for amiodarone has been long sought – a drug that is as effective as amiodarone, that still has minimal proarrhythmia, and does not have the bizarre toxicity profile of amiodarone.

For years, hope has been high for dronedarone, whose chemical structure is very similar to amiodarone’s. As it turns out, however, dronedarone is an imperfect substitute. While the new drug appears to have amiodarone’s low proarrhythmia potential, and while it thankfully has none of amiodarone’s unique side effects (and indeed, appears to be quite well tolerated), dronedarone is not as effective as amiodarone.

Still, it has a decided advantage over amiodarone (much less toxicity) and over other antiarrhythmic drugs (low proarrhythmia), so in many patients who have AF it seems like it might be worth a try. It might not be effective in as many patients as amiodarone, but for those patients in whom it is effective, well, it’s effective. And if it doesn’t work well enough, you can always switch to something else.

Indeed, that’s how antiarrhythmic drugs ought to be used most of the time. Pick a drug that seems to provide the best available balance between effectiveness and side effects for a given patient and try it. If it is ineffective or causes problems, stop it and move to the next one. The more antiarrhythmic drugs that are available, the better the chance of eventually finding an adequate choice for your patient. (It is worth pointing our that once you try amiodarone, however, you are done with this trial-and-error strategy – once you are on amiodarone, you are, for practical purposes, always on amiodarone.) In any case, the appropriate choice of an antiarrhythmic drug, as in many areas of medicine, can only be made on an individual basis, and not on a population basis.

But alas, this is not how a Clinical Effectiveness Tribunal like NICE works. These Diets of Medical Quality will only look at the average response to a therapy within a population of patients and, seeing (for instance) that dronedarone may only treat 40% of AF patients effectively while amiodarone treats 60%, will deem dronedarone to be insufficiently effective to justify its additional expense. (Read NICE’s “appraisal document” on dronedarone for yourself.) NICE has determined that amiodarone is a suitable choice for the treatment of atrial fibrillation, and that there is no need for a drug like dronedarone (or, presumably, any new drug that trades a bit of efficacy for a toxicity profile that is much less extravagant than that of amiodarone).

Old-fashioned physicians like DrRich, who might reason, “An initial trial of dronedarone would likely spare 40% of my AF patients from having to be exposed to the horrific toxicities of amiodarone, so perhaps it’s worth a try,” are hopelessly and irredeemably of low quality, and aren’t worth bothering over.

And as for the Smurfs and Smurfettes on amiodarone, despite their breathing difficulties, unsteady gaits, inability to see at night, and severe skin photosensitivities which preclude their Florida or Arizona vacations, at least their anguish over not being allowed a viable and available alternative will be temporary. For the drug companies, seeing how a Posse of Clinical Excellence operates, will take the only logical business step remaining to them and severely curtail their development of drugs aimed at offering incremental improvements over the current choices.

There will be no alternatives to agonize over, and everyone will be happy. This, DrRich thinks, is the plan.