Not Just Any Joe Smith

DrRich | December 3rd, 2010 - 10:28 am

DrRich is delighted to note that a very good and longtime friend and former colleague has been named as one of the HealthLeaders 20 for 2010 – that is, as one of 20 people, chosen by HealthLeaders Media, who are changing healthcare for the better.

DrRich has known this man for nearly two decades, and from the very beginning he has insisted his real name is Joe Smith. So let’s go with that.

Joe’s recognition by HealthLeaders is very well deserved. Joe is chief medical and science officer of the West Wireless Health Institute in San Diego, a non-profit institution whose mission is to bring wireless technologies to the patient, technologies to diagnose, monitor and treat health conditions in the patient’s own home. Joe is uniquely qualified for this role, having earned a PhD in medical engineering and medical physics, an MD from Harvard (a place DrRich has never even been allowed to see), and having spent years practicing medicine as a (particularly well known) cardiac electrophysiologist. (Electrophysiology, as regular readers will know, is widely recognized as the geekiest of medical specialties.)

For what it’s worth, DrRich considers Joe to be one of the most honest, most ethical physicians he has ever known, one who will always place the welfare of patients ahead of his own treasure and his own career. DrRich has seen him do it.

Significantly, one of Joe’s chief goals at West Wireless is to use advanced biosensors, attached to wireless communication, to lower the cost of healthcare. This can be done in at least two ways. First, by using wireless healthcare to keep patients healthy longer, and thus reduce hospitalizations and other expensive healthcare services; and second, by making at least some of these technologies available as consumer products, used by patients as they see fit for their own benefit, so they become part of the general economy (like toothbrushes and televisions).

DrRich is particularly pleased that Joe’s efforts are being recognized as worthy, since DrRich himself has devoted much of his professional effort to biosensors and wireless healthcare for the past 10 years.  Indeed, at one point he had the pleasure of working together with Joe Smith in this area.

The Top 20 healthcare leaders to which Joe has been named is an eclectic group. It includes John Goodman, another of DrRich’s heroes, as well as a couple of people readers of this blog would recognize as individuals whom DrRich would not consider as “changing healthcare for the better.”

In any case, please go read the HealthLeaders write-up of Joe Smith and his cutting-edge work at West Wireless. Congratulations, Joe!

The Proper SYNTAX For the GOD Panelists

DrRich | September 17th, 2010 - 8:27 am

Podcast:

In his last post, DrRich suggested that the Guideline Wars (i.e. the bloody battles over who gets to establish the patient-care guidelines that determine which patients will get which medical services, and which medical specialists will get to provide them) are about to enter the Obamacare phase, in which those who make the guidelines will no longer be medical professional organizations, but agents of the federal government. DrRich helpfully labeled the various guideline panels provided for by the Obamacare legislation as the “GOD panels” (for Government Operatives Deliberating), in order to avoid using the more inflammatory “death panels” terminology favored by certain less sophisticated commentators.

In addition, DrRich pointed out that his own tribe of medical specialists – the cardiologists – may perhaps be in a better position than most other physician tribes to manipulate the deliberations of these GOD panelists. The cardiologists would attempt such manipulations, DrRich suggested, by “pre-spinning” certain critical data from clinical trials, before that data is taken up by the government panels.

From their long experience in fighting the Guideline Wars, cardiologists understand that data from clinical science does not invariably lead to a fixed conclusion (as most proponents of evidence-based medicine seem to believe), but rather, can often be shaped into whatever sort of conclusion one might want to reach. Just as different primitive cultures discerned different constellations when they looked up into the same night sky, so will different groups of experts come to different conclusions when they look at the same clinical data.

Accordingly (DrRich submits), cardiologists have already embarked on the task of pre-spinning the data, such that when the GOD panelists look for the first time up into the vast and chaotic sky of clinical evidence, they will have in hand a map of the constellations as seen by the cardiologists.

To illustrate what he means, DrRich calls his readers’ attention to the SYNTAX trial, a clinical trial designed by cardiologists and their industry partners for the purpose of reaching a specific conclusion, but which (unfortunately for cardiologists) reached the opposite conclusion. If the data from the SYNTAX trial should ever fall into the hands of the GOD panelists (or any other guideline panels) in a pristine fashion, it could spell disaster. So the cardiologists have spent nearly two years attempting to make the data say what they want it to say, and today, after continuously massaging the data, issuing press release after press release, making presentation after presentation, and publishing academic paper after academic paper, it would be at least a little surprising if the God panelists, surveying this body of pre-spun data, would fail to produce clinical guidelines which provide the cardiologists at least some of what they’re after.

The SYNTAX trial randomized 1800 patients with complex coronary artery disease (i.e., CAD that produces either significant blockage in the left main coronary artery, or severe triple-vessel disease) to therapy with either bypass surgery or drug-eluting stents (DES), and assessed their long-term outcomes.

In general, patients with stable CAD (i.e., those who are not currently having a heart attack or unstable angina) do just as well with aggressive medical therapy as they do with invasive therapy. People like the ones enrolled in SYNTAX, however, are the exception to this rule. That is, patients with either of these two specific patterns of complex CAD have been shown to have improved survival if they receive bypass surgery. Indeed, these patients represent a virtual “last stand” for cardiac surgeons – they are nearly the only patients cardiologists (at least some cardiologists) still feel obligated to refer for bypass surgery. And, as one might expect, in their decades-long turf war with cardiac surgeons (a war from which they will not desist until they see the great majority of cardiac surgeons seeking jobs as beer vendors at sporting events), cardiologists have long chafed at this singular remaining obligation to refer.

Accordingly, SYNTAX, a study instigated by cardiologists and sponsored by Boston Scientific (a manufacturer of DES), was intended to show that with modern cardiac stents, stenting yields outcomes that are not significantly inferior to bypass surgery in these patients. Specifically, that is, SYNTAX was designed as a “non-inferiority trial.” This was certainly a modest goal – some might say too modest – but a positive result would enable cardiologists (the gatekeepers to all invasive CAD therapy) to simply keep these patients for themselves, just as they now do with all the other CAD patients. The SYNTAX trial asked the question, “Do I really have to refer these patients to the cardiac surgeon?” And the desired answer was, “No, it apparently is not statistically provable that you absolutely have to refer them, one supposes.” Judging from the study design, that answer would have been plenty rigorous enough for the study designers.

Alas, however, when the one-year follow-up data for the SYNTAX study was analyzed, the results turned out to be negative; stenting was significantly inferior to surgery. The endpoint of the study was a composite called MACCE (Major Adverse Cardiac and Cerebrovascular Events), and in this study included death, heart attack, stroke, and the need for more revascularization procedures. The bottom line is that in SYNTAX, the risk of MACCE was significantly higher for stenting than for bypass surgery. The study failed to meet even the modest non-inferiority goal the cardiologists had devised for it.

The one-year data for the SYNTAX trial was published in the spring of 2009 in the New England Journal of Medicine, just as the battle over healthcare reform was taking shape, and nearly six months after Sarah Palin had reported her mysterious vision of death panels. But whether one wanted to call them death panels, GOD panels, or panels of distinguished monkeys, it was clear by the time SYNTAX was published that the government, and no longer the physicians’ own specialist organizations, would be manufacturing all clinical guidelines in the near future. So disaster loomed.

But, the cardiology community quickly rallied, and launched into a concerted effort to spin the results of SYNTAX from a disaster into a victory, or at least, to something akin to victory. And the efforts of the cardiologists in this regard have been impressive over the last 18 months.

Within minutes of the publication of the original SYNTAX article, scores of press releases were launched, and scores of “experts” were dispatched to give interviews, implying that the SYNTAX study was a major, ground-breaking victory for stenting.

For instance, here’s the link to an article in the New York Times (subsequently reproduced in hundreds of newspapers around the country) entitled, “Heart Stents Found As Effective As Bypass For Many Patients.”

And here’s a triumphant press release from Boston Scientific, the study’s sponsor, in which the negative overall results of SYNTAX are buried deep within the 6th paragraph (following all kinds of positive-sounding fluff), and are difficult to locate even if you are specifically looking for them.

And here’s the more-than-triumphant press release from one of the leading clinical sites for the SYNTAX trial, which reads, in part:

“At NorthShore, we experienced stunning outcomes [emphasis DrRich's] in patients whose only option would have previously been bypass surgery,” said Ted Feldman, M.D, F.S.C.A.I., Director of Cardiac Catheterization Laboratory, NorthShore University HealthSystem, and a lead investigator of the trial. “The data in this study will provide cardiologists with additional information as they determine treatment therapy for patients with complex CAD.”

Most remarkable of all, we have the spectacle of the lead author of the SYNTAX paper, Dr Patrick W Serruys himself, telling Heartwire immediately after publication of the paper, that the paper’s concluding sentence (i.e., “CABG as compared with PCI is associated with a lower rate of MACCE at one year among patients with three-vessel or left main coronary artery disease (or both) and should therefore remain the standard of care for such patients.”), is just plain wrong. Serruys declared that this concluding sentence actually “is not the essence of the trial.” He only allowed that concluding sentence to appear in the paper, he said, “because the New England Journal of Medicine wanted something more conservative.” (Apparently, having the paper appear in a prestigious journal overrode the necessity of having the paper accurately reflect what the authors meant to say.)

In any case, Serruys insisted (despite the conclusion expressed in his ink-not-yet-dry paper) that many patients like the ones enrolled in the SYNTAX trial can safely be treated with stents, and indeed, he announced that he and his co-investigators were hard at work teasing apart the SYNTAX data in order to develop a so-called “SYNTAX score,” that would help cardiologists determine which patients they can treat themselves, without referring them for surgery. So indeed, despite the negative results, and despite the conclusion written in their own paper, the SYNTAX trial was immediately spun by key trial participants themselves into a win (while not a complete victory, still a win).

Before his readers come down too hard on the cardiologists for such behavior, DrRich feels obligated to point out a partially mitigating truth. Namely, cardiologists believe to the depths of their souls, notwithstanding the largely negative body of medical literature to the contrary, that stenting coronary artery blockages – in virtually any configuration and any clinical situation – saves lives. And if they haven’t been able to prove that yet, it’s just because of the vagaries of clinical research. One must not let spurious results from imperfect research block the Truth, lest one allow great harm to come to humanity.

The results of the SYNTAX trial must simply be wrong, cardiologists believe, and so they would be gravely harming patients if they did not take whatever steps were necessary to render the results of SYNTAX more favorable to stenting. To do otherwise would cause thousands of clinicians to make inappropriate decisions.

In this way, DrRich believes, cardiologists are no more guilty than are Progressives, another category of humans who believe with their hearts and souls in something that is simply not true (in the case of Progressives, that the great mass of humanity will willingly suppress their own individual interests in favor of the interests of the collective). Like the Progressives, cardiologists are often very nice, well-meaning, sensitive and compassionate individuals, and some of them would even be fun to go out with for a beer.

In other words, DrRich pleads, cardiologists are not being particularly evil in spinning the SYNTAX trial results; they are simply doing what comes naturally, and what they deeply believe to be the right thing.

This is why the SYNTAX investigators were convinced that, buried within the vast body of clinical data the SYNTAX trial has generated, there simply MUST be something useful to cardiologists. Accordingly, the SYNTAX investigators dived head-first into the proverbial room full of manure, enthusiastically digging for the pony which simply must be in there somewhere.

And indeed they quickly found their pony.

And here it is: While a straightforward analysis of the SYNTAX study shows that bypass surgery wins hands down over stenting, if one delves a bit deeper into the data, one finds that one of the components of the MACCE endpoint – the incidence of stroke – was statistically higher among the patients randomized to bypass surgery. One also finds that the incidence of needing revascularization during follow-up was higher in the stent patients. So, taking these two interesting observations together, the cardiologsts have concluded that patients receiving bypass surgery are trading a reduced need for subsequent revascularization for an increased risk of stroke – a bad trade indeed. Therefore, despite the overall results of the study, they have concluded that stents are better than bypass surgery for at least some patients. (And they promised to discover for us, during the data-mining exercise from which their “SYNTAX score” was subsequently invented, which patients those are.)

And this – the reduced incidence of stroke seen in the stent patients – is the basis for the celebratory statements which were issued by the SYNTAX investigators upon publication of their original paper.

DrRich agrees that, as a general proposition, he would probably rather have an extra invasive cardiac procedure than a stroke, and suspects that most people would say the same thing. But before we all buy what cardiologists are selling here, DrRich would like to make a few observations.

First, the results of the SYNTAX trial are the results. Stenting did not meet even its modest non-inferiority endpoint, and it failed to meet it by quite a lot. Once the pre-designated endpoint of a randomized clinical trial is determined, any remaining observations that can be gleaned from the large amounts of data invariably generated by such trials must be viewed as inconclusive, as merely hypothesis-generating. Such observations are not to be regarded as having sufficient statistical surety to vastly change medical practice, or to figure into evidence-based guidelines. So, another clinical study would need to be conducted to prove the hypothesis that strokes are less frequent with stenting than with bypass surgery in patients like these.

Similarly, the “SYNTAX score” – which indeed was generated and subsequently published as a “guide” for cardiologists treating patients with complex CAD, and which is therefore presumably being used today by cardiologists all over the world to select which of these complex patients they can just go ahead and stent rather than refer for bypass surgery – has no business being incorporated into clinical practice. An exercise like this – in which investigators comb retrospectively through the clinical data, selecting out patients who had good results with stenting, then devising a group of characteristics that appears to differentiate them from those who did not – cannot possibly yield a validated, widely-applicable clinical tool. If they want to claim that their SYNTAX score is clinically useful, they need to conduct another randomized clinical trial to test that hypothesis.

Next, and most remarkably, there’s the almost universally-ignored fact (reported by Dr Friedrich W Mohr, co-principle investigator of the trial), that among patients assigned to bypass surgery in the SYNTAX trial who experienced a stroke, nearly half of them had their strokes PRIOR TO SURGERY. What this means is that, in reality, the bypass surgery itself did not cause those strokes, a fact that ought to cause serious damage to the chief assertion of the stent-proponents. This fact alone turns their pony into a pig. The claim that stenting instead of surgery would have avoided these strokes is largely, if not entirely, spurious. Indeed, if anything, the fact that patients “randomized” to surgery apparently had a lot of strokes in the brief period of time between the act of randomization and the surgery itself ought to make one question whether the selection of therapy was really and truly random, or whether, somehow, patients who looked particularly sick got sent preferentially to the surgeons.

And finally, the clinical choice as it has been starkly painted by many proponents of stenting – that the real trade-off in choosing between stenting and bypass surgery in these patients is the choice between the higher risk of stroke with surgery versus the higher risk of revascularization with stenting – is incomplete and misleading. Presenting the choice in this way clearly favors stenting, and this presentation entirely explains the positive press releases and subsequent media coverage of the SYNTAX trial. But this is not a valid comparison of risks for several reasons:

1) As noted above, the actual risk of stroke posed by performing bypass surgery in the SYNTAX trial has been substantially overstated for public consumption (by implying that the surgery caused those strokes, when half occurred prior to surgery).

2) Surgeons in the SYNTAX trial most often did not employ newer techniques now in routine use, such as off-pump surgery and LIMA grafts, both of which can substantially reduce the risk of stroke and other embolic phenomena.

3) Re-occlusion of the involved arteries (which occurred about equally in both groups in this study, and which spokespersons for SYNTAX seem to brush off as not such a big deal), is an entirely different phenomenon in patients who have received DES than it is in patients who have had bypass surgery. After bypass surgery, re-occlusion tends to occur gradually, and the patient generally experiences recurrent symptoms of angina. But in DES, re-occlusion much more commonly occurs acutely, and catastrophically, leading rapidly to permanent cardiac damage and often, to sudden death.

4) Item # 3 might explain why the composite endpoint of “death, heart attack and stroke” was equal in both groups, even though stroke was significantly higher in the surgery group. That is, in order for the math to work out, the remaining dyad of “death and heart attack” necessarily must have been higher in the stent group. As far as DrRich can tell, this point has never been discussed in public.

5) In order to avoid the catastrophic re-occlusions seen with DES, cardiologists now insist that their DES patients take long-term, even life-long, Plavix, a powerful blood thinner. As the purveyor of a patient-oriented website on heart disease, DrRich cannot tell you how many distressed and stented-up patients have written to him with the following lament:

“My doctor put in one of those drug coated stents and has me on Plavix. He says if I stop the Plavix I could die, and won’t let me stop it for any reason. But I need my gallbladder out because I keep having gallbladder attacks, and the last one gave me blood poisoning. My surgeon says I need the surgery but he won’t do it unless I stop Plavix, and my cardiologist says no stopping the Plavix for any reason. What can I do? Can they just take these stents out so I can stop the Plavix?”

There is no easy answer to this question, at least not that DrRich can find. The DES patient commonly is left in the middle of a pissing match between surgeon and cardiologist. The fear of the cardiologist is that when one stops Plavix, there is a risk of sudden, catastrophic thrombosis of the coronary artery. But surgeons simply cannot operate safely on patients taking this drug. Few cardiologists seem to explain this to their patients before placing DES.

And more to the point at hand, none of the cardiologists spinning the SYNTAX trial are explaining to the public the implications of long-term Plavix. Even if their claims that stenting yields significantly fewer strokes turned out to be accurate, the choice here is clearly NOT a simple one between a higher risk of stroke on one hand, and a higher risk of needing “revascularization” (if they survive the re-occlusion, that is) on the other. There’s a lot more to think about than that, and cardiologists who imply otherwise are being either disingenuous, or delusional.

Just last week, SYNTAX investigators reported on the three-year outcomes in patients enrolled in the trial. The results, similar to the one-year outcomes, remain strongly in favor of bypass surgery at three years, and indeed, the incidence of stroke in stented patients has “caught up” with the incidence of stroke in the surgery patients.

This persistently bad news still does not really phase the cardiologists, who are now saying that the results of SYNTAX don’t really apply any more in any case, because drug-eluting stents have been improved since the trial was done.

It would appear that the cardiologists are going for some sort of official announcement to the effect that that the results of SYNTAX are, for practical purposes, indeterminate, and that what is needed is a new clinical trial, in which patients randomized to DES will receive the latest generation of stents. (Since there is a new generation of stents every year or so, this entire process can be repeated as needed until the cardiologists finally get the results they’re looking for, at which point they can declare final victory and stop.)

Summary:

All medical specialists should take a lesson from the cardiologists. In an era in which specialist organizations will no longer be writing the clinical guidelines for their own specialty, it is necessary to aggressively pre-spin any important clinical data upon which the GOD panels will be deliberating.

Considering the SYNTAX trial as a case study, one sees how it is possible to take the most straightforward results from a very straightforward clinical trial and, if not turn a negative outcome into a positive one, at least introduce enough complications, nuance, spin and uncertainty to cause any self-respecting GOD panelist to hesitate in making a definitive pronouncement on those results. Then, if you couple all the uncertainty you’ve created with a loud call for yet another clinical trial – one that will take into account new equipment, new techniques, new scoring systems &c., and that promises to clear up all the confusion you’ve dug up as a result of the last clinical trial – then you stand a decent chance of at least getting a postponement on any new guidelines harmful to your cause.

And this, you neurologists, gastroenterologists, pulmonologists and all you other, less savvy medical specialists, is how one can manage the GOD panels.

How Cardiologists Will Manage the GOD Panelists

DrRich | September 14th, 2010 - 8:50 am

Podcast:

In quainter times, medical “guidelines” merely meant a set of general principles which doctors ought to keep in mind when deciding on the most appropriate medical care for their patients. But in recent years guidelines have come to represent reasonably firm expectations for medical practitioners. And doctors who fail to closely follow guidelines may not be looked upon favorably any more by insurance companies or Medicare.

Obviously, then, since the guidelines finally determine who gets what, when and how, controlling the guidelines (i.e., making sure the guidelines say what you want them to say) has become important to any interest group within the healthcare system. And nobody understands the critical importance of guidelines better than cardiologists, a group of which DrRich is a proud member.

In a valiant attempt to carve out as much turf for themselves as possible within a healthcare system driven by guidelines, cardiologists, through their powerful professional societies, have been vigorously fighting the Guideline Wars for two decades – well before most other medical specialties even recognized that a war was being fought. This long struggle has lent to the cardiology profession a certain level of experience and sophistication that may help them to preserve some of their hard-won turf, even as we move into a far more dangerous phase of the Guideline Wars, in which less robust specialties risk debilitation, and even extinction.

For, under Obamacare, guidelines are now to become far more than mere guideposts, or principles, or even strong expectations. They are to become handed-down and inviolable rules which will dictate the details of proper patient care, and which doctors must follow to the letter. Following this new species of guidelines as closely as scripture will be necessary for any doctor who wants to be officially tabulated as a “physician of quality,” who desires to be paid the going rates, and who would prefer to avoid fines or imprisonment for fraud (fraud being, of course, the failure to practice medicine according to the guidelines).

Whereas until now the Guideline Wars have been largely fought among various medical specialties competing for turf, from now on the major combatant in these wars will be the federal government. Under Obamacare, the official medical guidelines will no longer be determined by conflicted medical specialty organizations (which will always try to establish guidelines that cause the healthcare system to spend lots of money on their specialists), but instead by government panels, which will have their own obvious conflicts of interest.

Most observers of the healthcare system seem congenitally unable to recognize that a government bent on controlling the behavior of its citizens (in order to create the perfect healthcare system, which, in turn, is a necessary component of a perfect society) will be working under, if anything, more conflicts of interest than any other healthcare entity.  In particular, the government, and by extension its appointed panels, will be desperate to the point of apoplexy to avoid spending any money, at any time, for any medical services, any time they can get away with it. So ultimately, the widespread proposition that the government panels will be entirely free of any particular agendas, or conflicts, or prejudices, as they hand down the rules of medical engagement to physicians, is balderdash.

The abiding conceit of the government panelists, of course, is that they will behave in an entirely objective manner in rendering the guidelines of medical practice, and will simply follow the science wherever it may lead, without any prejudice whatsoever. That is, they will not actually create the guidelines, but will simply “discover” them, through the objective application of clinical science. In other words, under Obamacare, the “true” medical guidelines will be handed down not by flawed men saddled with conflicts of interest, but by the inherent properties of nature. The government panels will simply be interpreting nature, and will do so, unlike those conflicted physicians, without prejudice.

Indeed, DrRich will go so far at to point out that the Obamacare guidelines will come from GOD – Government Operatives Deliberating. Readers who think it is in poor taste to refer to these individuals – who will invent the guidelines which will determine life and death for so many of us – as GOD panelists should be reminded that other, less sensitive individuals have tried to label them “death panelists.” DrRich’s nomenclature is not only more descriptive, but is much kinder.

In any case, this is where cardiologists have a tactical advantage over most medical specialists as we enter the Obamacare phase of the Guideline Wars. For, in their decades-long struggle in those wars, cardiologists have discovered something that more naive and inexperienced medical specialists, as well as academics, and even most government advisers, are only dimly aware of. Namely, that there is no such thing as the objective application of clinical science. Inevitably, interpreting clinical science – which is among the most inexact of the sciences – incorporates inherent bias.

That bias can be applied either subconsciously or consciously, but one way or another it is applied. And the advantage the cardiologists have over other medical specialists is that they understand that, to have a better chance of getting what they want, they need to direct the application of bias in interpreting critical clinical trials, and they must do it aggressively.

At the highest levels, of course, the agents of the government understand the very same thing. This is why they are setting up their own panels to control the guidelines in the first place. And you can be sure they will choose their panelists carefully.

But DrRich (and his cardiologist friends) know that when the government panelists are being sworn in, they will not be told their true mission in stark terms. They will not be told, “Your job is to twist the eminently-twistable clinical data in any way you must in order to reduce spending on healthcare, no matter who is hurt by it.” This charge would be unacceptable to most of the individuals the government would prefer to choose as panelists, namely, proud and accomplished individuals with valued professional reputations to uphold (though, to be sure, with a proven track record of thinking about clinical science with the kind of bias the government appreciates).

Rather, the panelists will be told:

“Panelists! You have perhaps the most critically important job in all of healthcare, namely, reining in the counterproductive, harmful, wasteful activities of the self-serving medical profession, which is married to greed, and beholden to its evil partners in medical industry. Your job is to lead doctors (most of whom would do the right thing if they can be shown the way in a sufficiently forceful manner) out of the wilderness, and bring them to the path of righteousness. For we hold these truths to be self-evident: that good medical care is efficient medical care; indeed, it is parsimonious medical care; and this being the case, the proper interpretation of clinical science will virtually always show us that less is more. It is your job to interpret clinical science in that proper way, to show American physicians how to fulfill their primary moral obligation to the greater health of the collective.”

DrRich has already demonstrated that there are plenty of physician-ethicists in very high positions who completely buy this stuff. It will be no problem for the Feds to find as many of them as they want to populate the GOD panels, and indeed candidates are virtually tripping over each other to audition.

In any case, their government handlers will reassure all the panelists that they simply are to follow the science, while establishing very strong expectations as to where properly-applied science will inevitably lead. This procedure will be aimed at allowing panelists to maintain the soothing and necessary fiction that they are, in fact, functioning as unbiased agents of reason and logic, and are well-deserving of public adoration, and perhaps even of self-respect.

Cardiologists, battle-hardened Guideline Warriors that they are, understand the position in which the new GOD panelists will find themselves, and as a result they understand that the clinical science these panelists will use to fashion medical guidelines must not reach them in anything like a pristine condition. Rather, that clinical science must reach them “pre-spun,” with the “right” interpretations already spelled out for them by respected academic figures, and, to the fullest extent possible, already permeated into the public consciousness. Cardiologists hope that panelists will be relatively reluctant to make guidelines which are starkly opposed to such predisposed interpretations, for fear they will be found grating to professionals outside of government whose opinions they might value.

With such a strategy the cardiologists are perhaps clinging to a thin thread. It is, in fact, not much of a plan. But it beats whatever it is you gastroenterologists are doing.

In his next post DrRich will illustrate cardiologists’ new strategy of “pre-spinning” clinical trial data, in order to make it more difficult for GOD panelists to do them grave harm.

More Arguments for Withholding Crestor

DrRich | July 7th, 2010 - 7:34 am

Podcast:

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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Why They’re Trashing the JUPITER Trial

DrRich | July 2nd, 2010 - 9:29 am

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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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Mediating An Electrophysiology Dispute (With Bias)

DrRich | June 7th, 2010 - 6:41 am

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A minor dispute – and an extraordinarily (almost disturbingly) polite one – has developed between the only two other electrophysiologists, that DrRich knows of at least, in the blogosphere. DrRich, being the third, ought to weigh in – not because his “vote” would break the tie, but because (as always) DrRich knows best.

Dr. Wes started it all off with a post noting, with some degree of dismay, that “(b)oth the Department of Justice (DOJ) and the Recovery Audit Contractors (RAC) are focusing investigations on Medicare billing for implantable cardiac defibrillator (ICD) surgery.”  Wes, with an appropriate degree of paranoia, concludes,”Consider yourself warned, criminals,” then recalls the halcyon days when the prospect of spending time in court conjured up for physicians nothing worse than malpractice suits.

Dr. John M. counters with a post whose purpose is to “welcome the upcoming policing of cardiac device implants.” John goes on to chronicle several examples he has witnessed of physicians implanting ICDs when, clearly, they should not have. The investigations of ICD implants by the Feds – and their private counterparts, the RACs – John posits, will serve to root out the bad eggs.

To his credit, John allows right off that his post is published “at the risk of exposing my naivete.”

To which DrRich replies, “Indeed.”

When DrRich was young, his grandmother, an immigrant from the Old Country who never shed her rustic habits, and not owning a motor vehicle, kept an illegal henhouse in her garage, buying the silence of her neighbors with eggs. It was from her that DrRich learned that if a rooster is behaving badly – engaging in hen abuse, for instance, or perhaps chasing grandchildren around the yard – one does not deal with it by sending Uncle George’s pit bull into the henhouse to take care of the offender. While the nasty rooster (never one to avoid a confrontation) might well be taken down, so would a lot of innocent bystanders.

John, you are laboring under the charming delusion that the purpose of these new investigations is to carefully review ICD implants and tease out only those unethical and/or poorly-trained device implanters, who are clearly and habitually engaging in untoward medical practices. If this were the case, then you and Wes and all those other honest EPs would have nothing to be concerned about, and the audits would indeed make the world a better place.

But alas, DrRich must tell you otherwise.

First, he urges you to read about his own experience. DrRich is a bit older than you, John, and was around the first time the Feds decided to conduct such an “audit” of ICD implantations. DrRich – like you, as pure as the driven snow – was absolutely certain he had nothing to worry about. But as matters unfolded, the fact that DrRich is not today writing this blog from a federal prison (do they let you do blogs in the penitentiary?) is more a matter of luck than anything else.

This new “audit” is much more intimidating than the one DrRich endured. That one was done by the relatively benign Office of the Inspector General (part of HHS). This one is being done by the Justice Department. So if they finger you, you are by definition, as Wes suggests, a criminal.

DrRich has talked about the Regulatory Speed Trap many times. Regulations inevitably become obtuse by evolution if not by design, so that, if you are practicing medicine, it is likely that somewhere – in the hundreds of thousands of pages of indecipherable and self-contradictory Medicare regulations – you are guilty of failing to comply with a regulation somewhere or other, and thus are guilty of healthcare fraud – which is a federal crime. The only thing that likely separates you from a convicted (or, more likely, self-confessed as part of a plea bargain) criminal is that the Feds haven’t decided to “audit” you yet.

The Feds know this, of course. The fact that they know it is documented in a recent GAO report entitled “Improvements Needed in Provider Communications and Contracting Procedures.” The GAO report notes that the bulletins which Medicare carriers are required to send doctors periodically (to make sure they understand the regulations) are filled with dense, lengthy and poorly organized prose sufficient to make them unreadable. Even if they were readable, the GAO continues, these bulletins would do doctors little good since they routinely announce new regulatory policies well after the implementation date, when doctors will already have been guilty of violating such policies (and thus committing fraud). Finally, the GAO finds that when confused doctors contact the Medicare call centers for clarification on the regulations, they get the correct answer only 15% of the time. (Even the IRS does substantially better than that.) And the Medicare websites, required under the regulations to clarify everything for the providers, universally lack “logical organization and navigational tools,” and as a consequence are nearly unusable.

So even when a doctor prospectively asks for instruction on how to comply with Medicare regulations (so as to avoid committing healthcare fraud and incurring huge fines and jail time), nobody is able to give him/her a straight answer. For, while it’s easy to look at a provider’s actions retrospectively (as the auditors are about to do), and find something in the dense regulations that makes those actions imperfect, it’s not so easy to tell providers ahead of time how to navigate those regulations in pristine fashion. As the GAO report reveals, nobody knows how to do that.

Now, DrRich is not calling the DOJ evil. The Feds are not being evil when they set out to conduct audits of physicians’ compliance with uninterpretable regulations; indeed, from their way of looking at it they are being humane.

They are only doing what they have to do, which is find a way – any way – to reduce healthcare costs. In this instance they do not really want to label hundreds or thousands of electrophysiologists as criminals, and ruin their careers and their reputations and their lives. They just want to ruin a few, and make sure the other ones know about it. This limited-bloodshed approach will accomplish their goal, which is, to make all the other electrophysiologists think twice (or thrice) before using ICDs again, in anyone, ever.

But in this instance it gets even worse. With this audit, in addition to dealing with the relatively-restrained Feds, electrophysiologists will also be dealing with the slavering RACs.

The RACs are a fun tidbit brought to us by the Medicare Prescription Drug Act of 2003. Under the RAC initiative, private contractors are to be sent out to perform audits of billing already done by insurers, health plans and physicians. The objective is to find “overbillings,” which the providers will have to repay along with penalties. Further, the act explicitly allows for prosecutions to be brought for “fraud and abuse,” even if the providers have repaid any overbillings.

The purpose of the Recovery Audit Contractors is, well, recovery. During the 3-year pilot of the RAC initiative, which took place in only 3 states, over $300 million were recovered. This wonderful success is the reason RACs are being turned loose elsewhere.

The RACs are paid by commission. Essentially they are bounty hunters, and they get to keep 20% of whatever they collect. According to the Associated Press, hospitals and providers are just a tad worried that these contractors, being so generously incented, will prove a little overzealous in their enthusiasm to find fraud. But worried auditees should not look for sympathy from the public. “A little zealotry is what we’re looking for on the part of the taxpayers,” said Leslie Paige, spokeswoman for Citizens Against Government Waste. “We think it’s about time.” Indeed – everybody can get behind fighting fraud, which is what makes the fraud gambit such a powerful tool for covert rationing.

DrRich surmises that it is good to be a RAC, and thinks you should consider buying stock in these companies, if you can. These outfits are about to harvest the vast bounty of obfuscation that Medicare has been carefully cultivating in its regulations for over 40 years, and has been carefully fashioning as fraud-traps for a somewhat shorter period of time. The RACs see the vast herds of physicians (violators one and all) placidly grazing all across the fruited plains, just waiting to be harvested. Their chief problem will be in pacing themselves; showing some restraint so they don’t use up their resources all at once.

And so, in addition to the dogged, officious, unsympathetic countenances of the lawyers employed by the DOJ, electrophysiologists this time around can also look forward to seeing the leering faces of the RACs’ commission-drunk forensic accountants. Electrophysiologists will experience the worst excesses of both worlds – the excesses of the state, and the excesses of unfettered for-profit outfits.

John M. can welcome this if he wants, and DrRich will wish him the very best good luck. DrRich, though, is still a little shell-shocked 15 years after his own encounter with federal audits of medical practices, and is very glad he’s only a spectator, and not a participant, this time around.

________________________________

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!

Neuroscientists Beware! Here Come the Cardiologists!

DrRich | May 29th, 2010 - 10:24 am

Podcast:

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.

The Individual Mandate Will Stand

DrRich | March 25th, 2010 - 6:58 pm

Podcast:

People who do not like the new healthcare system our government is establishing for us intend to formally challenge the constitutionality of one of its major provisions, namely, the “individual mandate” – the provision that all individuals must purchase health insurance.

The grounds for challenging the individual mandate, essentially, is that the Constitution does not grant the federal government the authority to compel legal residents of the U.S. to purchase a particular product, or enter into a particular contract, simply as a matter of their being legal residents. For many of those who object to the new healthcare law, the individual mandate goes to the principle reason for their objections – that the government has assumed for itself sweeping new powers that directly impinge on the liberty of individuals.

DrRich himself feels this way. If the government can make us buy a product against our will for the sake of the common good, then a firewall will have been taken down, and DrRich does not see any fundamental barrier to the government being allowed to compel us to any action it deems to be for the common good.

For instance, since your obesity, by sucking up limited healthcare resources, will impinge on DrRich’s ability to get whatever healthcare services he thinks he might desire, DrRich can now legitimately petition the government to regulate your intake of Twinkies. You fatty. And as for all you overweight middle-aged women out there, who habitually fail to perform the hour-per-day of exercise that best medical evidence insists you perform, it would be entirely appropriate for the President’s proposed army of college-age zealots – the Civilian Service Corps or whatever he’s going to call it – to show up every day to organize you and your similarly-shaped neighbors into ranks, for hour-long forced marches.

You may think DrRich exaggerates. DrRich hopes so, too. But he’s not sure.

In any case, for those among his readers who do not want any constitutional challenge of the new healthcare law to succeed, DrRich has good news. It won’t.

DrRich has come to this conclusion after reading the section of the law that deals with the individual mandate. This section, “Subtitle F – Shared Responsibility For Health Care,” is carefully designed to defeat any constitutional challenge.

The meat of Subtitle F is contained in one sentence (Section 5000A), to wit: “An applicable individual shall for each month beginning after 2013 ensure that the individual, and any dependent of the individual who is an applicable individual, is covered under minimum essential coverage for such month.” This sentence takes up about 20% of one page. Most of the remaining 42.8 pages of Subtitle F creates a protective shell against constitutional challenge. It does this in two ways.

The first protection against a constitutional challenge is the more obvious. In fact, before we ever get to the individual mandate itself, we are treated to five pages that detail the multitude of ways in which “individual responsibility” in healthcare (i.e., the mandate to buy insurance) “is commercial and economic in nature, and substantially affects interstate commerce, as a result of the effects described in paragraph (2).” In other words, the individual mandate is wrapped by a formal “finding of Congress” that this mandate is subject to the Commerce Clause of the U.S. Constitution.

DrRich is not enough of a legal scholar to understand whether the five pages of justification that follow (the “paragraph 2,” referred to above) are sufficiently compelling to actually invoke the Commerce Clause. To him, it all sounds like an “ends justifies the means” argument, one that would be equally applicable if Congress decided it would benefit the general welfare to mandate that people purchase all their cars from Government Motors. But whether or not the supportive language itself proves compelling to the courts, it seems very unlikely to DrRich that the Supreme Court would overturn a formal “finding of Congress,” as regards the applicability of a provision of Congress to the Commerce Clause.

But this first protection against a constitutional challenge only covers the first five of the 43 pages of Subtitle F. Most of the remaining 38 pages establishes the second protection. This one is more subtle than the first, but, DrRich thinks, it will be the more difficult one to overcome.

That remaining portion of Subtitle F deals largely with the penalties to which individuals would be subject if they failed to comply with the mandate to buy health insurance. It describes in detail how the mandate is to be complied with, how compliance is to be documented, and how the mandate is to be enforced. This long section of Subtitle F reads like tax law, like IRS code. As well it should. For, what it establishes is that the individual mandate is actually a tax, that is treated like any other tax in its documentation, collection, and enforcement, and indeed, that the IRS will be running the whole show.

If DrRich were defending the individual mandate before the Supreme Court, here is what he would say.

“Your Honors (and you other Justices, too), even if you find that the Commerce Clause is not applicable here (a finding, I respectfully submit, which would create a Constitutional crisis, since Congress has issued its own formal finding to the contrary), you must let this provision stand for an even more compelling reason, which is: This is not really an individual mandate to purchase health insurance or any other product, as our opponents claim. It is, in fact, simply a tax, like any other tax.

It is a tax. A healthcare tax. It is a tax to support healthcare in the United States, payable to the U.S. Government on Form 1040, administered and collected entirely by the Internal Revenue Service. It is not in any way fundamentally different from the Medicare and Medicaid taxes, which also support healthcare services for our citizens, which also appear on Form 1040, and which are also administered and collected entirely by the IRS.

Your Honors, simply look at the language of Subtitle F. After a modest amount of palaver to convince Your Honors that the Commerce Clause applies (and, I remind you, it does), the last 38 pages of this Subtitle is tax law. I mean, really, just try to read it. Can any of you understand it? Neither can I. It’s IRS tax code, plain and simple.

The only difference between this tax and any other federal tax is that Congress, in its wisdom and magnanimity, gives the individual citizen the ability to opt out, to not have to pay it, simply by documenting that they have purchased health insurance. That is, if the citizen chooses to buy health insurance – which, we must all admit, would be a wise decision from that individual’s point of view, as well as a benefit to society – the IRS will forgive the new healthcare tax altogether.

Where is the mandate here? Nowhere in Subtitle F does the word “mandate” appear. Rather, Subtitle F refers to “shared responsibility.” Individuals should feel responsible to do their part for society as a whole, and this Subtitle encourages them to act on that responsibility. They can do so by paying the new healthcare tax. Or, if they choose, they can do so by making sure they and their families are covered by health insurance. To be sure, Congress’ intent was that the large majority of citizens would choose the latter. But for all that, it is in the end the individual’s choice.”

As much as DrRich wishes otherwise, the individual mandate in the new healthcare law has been written in such a way as to almost certainly turn aside any challenges based on its constitutionality.

So, ladies, form your ranks and start marching that fat off. Hep-two-three-four.

Amiodarone is not NICE

DrRich | January 10th, 2010 - 8:41 pm

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.