Limiting Crestor

November 18th, 2008 by DrRich

In a previous post, DrRich wrote about the JUPITER trial, the controversial clinical trial (so controversial that even Stephen Colbert did a riff on it) which showed that the (extraordinarily expensive) statin drug Crestor significantly and substantially reduced the risk of heart attack, stroke and death in people who had normal cholesterol but high CRP levels.

While many prominent medical figures have defended the JUPITER trial as being well-designed, well-conducted, and productive of very compelling results, and have therefore concluded that doctors should take this information into account when treating their patients, and have even called for the guidelines on statin therapy to be formally revisited, other prominent figures tell us that we must dismiss such ridiculous opinions as coming from mere shills and puppets for the pharmaceutical industry.

But, as DrRich showed in his earlier posting with his characteristic thoroughness and impeccable reasoning, those who wish to dispel the notion that Crestor should be ground up and mixed into everyone’s toothpaste are taking the wrong tact when they simply try to make the results of the JUPITER trial go away.

Sure, we might all wish the sponsors and investigators had also studied one of the cheap statins in this trial, or had included an arm within the trial that would have told us whether doing expensive CRP testing was really necessary, but we cannot be legitimately angry with them for doing what they did. After all, it’s the system we’ve purposely laid out for the drug companies that requires them to invest tens of millions of dollars in trials like this before they’re permitted to sell their products. So we can scarcely criticize them when they comply with the prescribed system by designing their trials to test only their own products. (Let those other companies run their own trials, at their own expense.)

The sad fact is, as much as we may not like the study’s design, there is no denying that when you give Crestor to people like the ones enrolled in the Jupiter trial, their clinical outcomes will be significantly improved.

So let’s just cut to the chase and admit that despite the fact that we would spare nearly 35,000 JUPITER-like Americans a heart attack, stroke or death each year by giving several million of them Crestor, we just don’t want to pay the $7 billion per annum it would cost us to do so. (Heck, it would be only half as expensive to send each of the affected spouses a condolence payment of $100,000, and who’s to say many of them wouldn’t appreciate that consolation more than they would appreciate receiving a free lifetime supply of Crestor for those lumps on their couches?)

The question, then, boils down to this: Given that we have no intention whatsoever of buying our fellow Americans all that Crestor, in the face of the results of the JUPITER trial how are we going to justify that intention, to ourselves and to others?

DrRich has spent a good bit of time reading the various arguments experts (and others) have advanced to justify not purchasing the prodigious amounts of Crestor which the JUPITER trial was designed to coerce us into purchasing. He believes these arguments can be summarized into two general categories.

Why we should limit Crestor: Argument 1.

The first general argument is the notion that in the JUPITER trial, the benefit imparted by Crestor really didn’t do that much good after all, so bothering about placing millions of people on Crestor just doesn’t make sense. There’s just no need to consider the matter any further.

DrRich, of course, answered this argument in his previous posting. Simply put, the argument is statistically spurious. It requires ignoring the actual statistical analysis presented in the JUPITER paper itself,  and instead considering only the data as it was misrepresented in (or perhaps misinterpreted from ) the accompanying editorial. And, even if you allow the misrepresented data, the magnitude of benefit imparted by Crestor in this population is (considering the sheer number of Americans who would be spared a cardiovascular catastrophe if they took the stuff) still quite substantial.

In the days since publishing his last article, DrRich has done a bit of research to see what the magnitude of benefit is said to be for a well-known comparable therapy, one that is not only widely used in modern medicine, but is also celebrated as perhaps the most important preventative medical therapy yet devised - the treatment of hypertension. Americans are all urged to have their blood pressure checked beginning at a very young age, and if they have hypertension they are urged to have it treated aggressively. Scores of clinical trials have been done looking at the benefits of treating hypertension, and DrRich knows of no physicians, professional organizations, or even nihilistic consumer groups (such as exist to castigate statins) who say that treating hypertension is not worth the effort.

As it turns out, aggressively treating moderate hypertension (diastolic blood pressures of 90 - 100 mmHg) for five years yields a relative reduction in cardiovascular events (heart attack and stroke) of between 16% - 40%, and an “absolute” reduction in risk of 0.7% - 1.3%.  Well, what do you know? That’s pretty much the same as the relative and absolute risk reductions  resulting from Crestor (even allowing the unfortunately-presented summary of data from the JUPITER editorial), except the benefits with Crestor are accrued after only two years.

If we’re going to argue that using Crestor in JUPITER-like patients just doesn’t do enough good to bother with, then to be consistent we’ll have to also abandon all the anti-hypertension hype we’ve all been promulgating for 30 years. (DrRich uses the word “hype” advisedly. By the same criteria of data analysis being urged upon us by critics of the JUPITER trial, the massive public health campaign on hypertension we’ve been so deeply engaged in - and paying for - for so many years can only be considered hype.)

If we can save a bundle by withholding Crestor, just think of how much we can save by withholding the treatment of hypertension.

Why we should limit Crestor: Argument 2.

The second general argument is that we shouldn’t pay for Crestor because individuals could achieve similar benefits “simply” by choosing to engage in healthier lifestyles. All they need to do is stop smoking, exercise vigorously for 30 - 60 minutes per day, attain an ideal weight, eat an exemplary diet, and have their hypertension, cholesterol levels, and diabetes optimally treated. Because people have it in their power to control these important factors, they should do so, and we should not discourage them from doing so by providing them with a pill to achieve similar benefits. Providing them with such a pill (apparently) would be fiscally irresponsible, morally irresponsible, or both.

DrRich finds that this is not a completely illegitimate argument.  People should take responsibility for their own health, and perhaps should not expect society to bail them out when they develop one degenerative disease or another because their lifestyles are not completely exemplary.

However, if we are to make this the official policy of our healthcare system, then we certainly would not stop with Crestor for elevated CRP levels. To be consistent (and the whole point of “tough love” is to be consistent), we would also need to withdraw therapy for most people with hypertension, type II diabetes, stroke, heart disease, metabolic syndrome, lung diseases, liver diseases, sexually transmitted diseases, osteoporosis, trauma, and numerous other conditions often associated with lifestyle choices.

Talk about saving ourselves a bundle.

Here is the bottom line as DrRich sees it: Any healthcare (or political) policy that relies on a fundamental change in human nature is doomed to failure. (If this were not universally true, then Communism would have worked out just great in one place or another.) We can encourage and educate people about their lifestyle choices. We can even incent them to make good choices. But we can’t have a realistic healthcare system that insists or relies upon every person making those good individual choices.

So, while refusing to purchase medical services for people who could help themselves by choosing healthy lifestyles is not a completely illegitimate approach, it is an approach that we need to consider very carefully given its certain negative outcome. And for us to attempt to force this approach not generally, but instead to one specific medical condition or one specific therapy, and for completely arbitrary reasons, is perhaps feasible but is hardly morally or logically defensible.

Besides, the JUPITER investigators inform us that Crestor worked just as well in patients who apparently did follow reasonable lifestyle recommendations. So we might end up having to give the stuff to people whether or not they live the way we insist they live.

The right approach

It is not wrong for us to balk at spending $7 billion each year on Crestor. We would be crazy not to balk at it. It’s just that neither general argument advanced by the opponents of JUPITER seems very satisfactory, and in fact, to DrRich they seem completely bereft of merit.

It is likely not appropriate for us to spend all that money on Crestor for the amount of benefit that we would stand to gain. But it’s not because there isn’t substantial benefit to be had, nor is it because people just need to take better care of themselves before asking us for any healthcare.

What we’re really asking ourselves is whether Crestor is one of those healthcare products that ought to be withheld in response to the absolute unavoidability of rationing. And there’s simply no good answer to this question as long as we insist on pretending that rationing is not necessary and is not already occurring, that is, as long as we insist on accomplishing the unavoidable rationing covertly. The abandonment of rational discourse and the enthusiastic adoption of self-delusion are inherent features of covert rationing, and both are on obvious display here.

An open, transparent system of healthcare rationing would allow us to objectively assess the merits and the cost of Crestor in patients with elevated CRP levels, and to compare those merits and costs to other, similar medical services - the treatment of hypertension, for instance. With such a system we could make disposition on the use of Crestor quickly and objectively, without the twists of logic and without appeals to Platonic ideals of human nature, as we’re seeing today. Perhaps even better, the transparency of such a system would finally focus companies away from developing products they believe they can coerce us, through the use of cleverly designed randomized clinical trials, into paying for. An open system of rationing would, for the first time, focus the innovators of medical technology on developing products that reduce healthcare costs. Today, under covert rationing, technology is instead employed - with great creativity and incredible efficiency - to produce a steady stream of high-margin products that offer only incremental benefits.

Calling for the adoption of a system of equitable, objective open rationing is relatively easy. Designing a system for doing so - not so much. So it would not be fair or reasonable for DrRich to insist on a system of open rationing without describing how such a thing could be accomplished. And so, in the interest of fairness and reasonableness, he reminds his readers that he has attempted to do so both in his book and on his other website. Other, smarter people could doubtless come up with even better systems. It would be difficult, though, to come up with a reasonable system of open rationing that is not less destructive than the system of covert rationing we’re engaged in today.

Posted in General Rationing Issues, Cardiology Topics, Evil Drug Companies | 8 Comments »

Crestor, Guidelines, Rationing and Other CRP

November 13th, 2008 by DrRich

The JUPITER trial, reported this week at the American Heart Association Scientific Sessions and simultaneously published in the New England Journal of Medicine, has created quite a stir in the mass media and in the blogosphere. DrRich would like to do his bit in flaming the controversy.

On its surface the study and its results are 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. Patients randomized to Crestor, after an average treatment period of 1.9 years, had a highly significant 44% reduction in a composite endpoint that included heart attack, stroke, the need for stenting or bypass surgery, and cardiovascular death. Both CRP and cholesterol levels were also significantly reduced in patients taking Crestor.

This study is noteworthy because it is the first large randomized trial to show that Crestor (or any 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 people 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 bears before they’re 30.)

So here’s what we know from the JUPITER trial: giving Crestor to patients similar to the ones enrolled in this study can be expected to significantly and substantially improve their cardiovascular outcomes, and in a relatively short period of time.

But, as with any clinical trial, this one does not answer all the questions that we would like to have answered.

This trial, for instance, does not tell us whether the beneficial outcome is specific to Crestor, or is a class effect of all statins. (DrRich believes it is very likely to be a class effect, since the statins all tend to behave similarly in virtually every other way.) This trial does not tell us whether reducing CRP levels is beneficial - it only tells us that giving Crestor to people with high CRP levels is beneficial. (As Dr. Centor points out, it is time to begin thinking of statins as plaque-stabilizing drugs instead of cholesterol-lowering drugs; their benefit may not rely on lowering either CRP or cholesterol.) It does not tell us whether using CRP as a screening tool is actually helpful. (Only patients whose CRP was elevated were enrolled in this study. Similar patients - that is, patients who tend to be overweight and have a fairly high incidence of metabolic syndrome and a relatively high incidence of smoking -  but with normal CRP levels, might have had the same outcome.) And this trial does not tell us the risks of lifelong Crestor therapy. (DrRich notes, however, that statins have been in widespread clinical use for nearly 20 years, and seem unlikely to hold very many surprises at this point.)

So there’s a lot we still don’t know, and much of what we don’t know would be important to any doctor counseling a patient who wants to reduce their risk of cardiovascular disease.

But still, there should be no controversy here. 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 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 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 (hopefully) become more and more effective. 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 we don’t practice medicine the way it ought to be. We practice it according to guidelines.

And this makes the stakes very high when it comes to a clinical trial like JUPITER. For guidelines do not generally permit a range of actions tailored to fit individual patients - they generally present a binary answer. In this case, the binary answer yields either no change in clinical practice (and no change in spending), or a change in clinical practice (and an increase in spending, on Crestor, amounting to several billion dollars a year).

So as one might predict, a controversy has broken out.

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 - 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 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. There is furthermore a subset of this group who believe that statins, in particular, are the devil’s work, and represent some sort of effort on the part of the pharmaceutical companies (all of which seem to market a statin of one variety or another) to enslave every American. These people, one can only surmise, would object to statins even if they were proven to cure heart disease, cancer, baldness, obesity AND to produce fine and durable erections upon demand.

DrRich simply points out 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 before they are allowed to sell a new product, or 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 AstraZeneca 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 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. From what DrRich has seen, most of the statistics 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 has thrown in a key summary sentence that has been greedily grasped by the antialterguidelinetarians, 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 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 will not make anyone wade through the reasons why, because he realizes that one or two of his readers might not enjoy statistical arguments. (Instead he will provide those reasons in this footnote.*) Suffice to say here 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 this widely-quoted summary statement by Hlatky suggests.

As illegitimate as this summary statement may be, let us accept it for a moment just for the sake of discussion, since that’s the data the antialterguidelinetarians 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. 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 it’s 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. 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 antialterguidelinetarians 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 outlined in the footnote.*  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, and the only real reason there’s any controversy 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 AstraZeneca 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 Corollary Four of the Grand Unification Theory of Healthcare: Covert rationing corrupts everything it touches.

*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 here - 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 analysing 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), 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 for 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.

Posted in General Rationing Issues, Cardiology Topics, Guidelines, Abuse of, Evil Drug Companies | 12 Comments »

Fun With Randomized Trials, and Breasts

July 18th, 2008 by DrRich

The Cochrane Collaboration has created something of a stir with its latest review on the advisability of doing breast self-examinations, which concluded, in essence, that they’re not advisable. Specifically, they found that women who perform breast self-examinations end up producing more harm than good, so women should be discouraged from the practice.

The Cochrane Collaboration is a highly regarded resource for those who value evidence-based medicine, medical guidelines, and the randomized clinical trials that support such tools. The experts at Cochrane conduct reviews of all randomized clinical trials (RCTs) that meet their strict criteria for scientific and statistical robustness, and periodically publish summaries of the scientific evidence thereby derived, on particular clinical topics. Cochrane reviews are thorough and straightforward, and virtually always present an accurate reflection of the up-to-date evidence as supported by RCTs.

Despite the respect in which the Cochrane Collaboration is held, DrRich finds it at least mildly interesting that their conclusions regarding breast self-examination have not been generally construed as being politically incorrect. After all, several aspects of political incorrectness, ones at least as incorrect as your more standard species of political incorrectness, can be readily identified within the Cochrane review. For example, one could easily allege that anti-women, anti-self-empowerment, or anti-early-detection thinking riddles this report. And if the review had emanated from say, the White House, one almost certainly would. But in fact most media reports, while expressing a certain amount of surprise, have seemed very reluctant to criticize the Cochrane Collaboration’s conclusions. And physician experts who have been excavated by the media for their comments have also given at least tepid support.

(Not all commentators have blindly accepted Cochrane’s recommendations. DrRich refers you to his colleague Trisha Torrey, for example, who expresses an appropriate amount of skepticism. But the traditional media, and their Rolodex physicians, have on the whole swallowed it. See here and here.)

The general support for Cochrane’s report on breast self-examination, DrRich submits, is a direct reflection of the exulted position that RCTs have achieved today all across the modern medical (and media) landscape. If a statistically legitimate RCT reaches some conclusion, no matter how strange, counterintuitive, or wrong that conclusion might seem, it is a conclusion that must be accepted. That this belief in RCTs trumps even the powerful social force of political correctness speaks to its ultimate strength.

DrRich has previously observed that our widespread belief in RCTs can be reduced to three main tenets:

1) Data derived from randomized clinical trials represents Truth.
2) Data derived from non-randomized trials represents Falsity.
3) If you don’t believe this, you are a heathen.

Objective observers will find it at least a little ironic that an attempt to claim the scientific high ground has so obviously resulted in a new religion, replete with its own dogma. True Believers will not see the irony, thus providing even more evidence that what we’re dealing with here is indeed a religion and not objective scientific thought. (Religions deal in mystery, and not irony.)

The sad truth is that the results of RCTs are invariably dependent on the bias built into their design, and even if internally they are statistically legitimate, they can often send us down the wrong path.

Those who design RCTs (the smart ones, at least) know this. They are like smart trial attorneys, in that they know the answer before they ever dare to ask the question. So they tailor their “question” in such a way as to yield the answer they want to get. Indeed, if a lawyer should end up asking a question that produces an unexpected answer, he or she is completely incompetent and ought to be sued for legal malpractice. In more cases than one might think, the same is true for those who design RCTs.

So, for instance, if you are a payer and want to limit the use of an expensive therapy, you design your RCT so that enrolled patients likely to respond to the therapy are diluted with lots of enrolled patients much less likely to respond, to assure that the average response of the whole population will be quite small. (In many instances the clinical characteristics of the likely responders and the likely non-responders will be reasonably apparent.)

On the other hand, if you are a company that wants to encourage the use of your product, you design an RCT that preferentially enrolls patients who are very likely to respond favorably, and then trust the marketplace (with a tweak from your DTC advertisements) to “extrapolate” the results to broader categories of individuals.

So RCTs do not in any way eliminate statistical bias, as most seem to think. Rather, they simply offer an opportunity to control the statistical bias in your favor. Since most doctors (and most regulators, guideline writers, and reporters) don’t seem to get this, it becomes relatively easy to fool them.

DrRich does not know if the people who designed the RCTs looking at breast self-examination tried intentionally to bias the results against self-examination, or if it was an accident. But that is what they did.

The RCTs which the Cochrane Collaboration reviewed looking at breast self-examination indicate that, in large populations of women in Russia and China, who go on to receive Russian and Chinese healthcare, breast self examination did not improve overall survival. And since those who did self-examination underwent twice as many breast biopsies, many of which revealed benign lumps, they experienced net harm. DrRich does not quibble with any of this. It is almost certainly true.

On the other hand, while most RCTs do not reveal it (since they look at aggregate results and not individuals), it is most often the case that some individual participants in even a negative study will experience benefit from the intervention being tested. In the breast-self examination studies, for instance, it is a certainty that individual women benefited at least to the extent that their breast cancers were detected earlier than they otherwise would have been. (In the Russian study this was proven to be the case.) These women had at least a shot at better survival by virtue of their earlier detection.

But whatever the overall results of these RCTs conducted in such exotic locales, they can have nothing whatsoever to do with women in America in 2008, who receive far more aggressive, tailored, and sophisticated therapy for breast cancer than women in virtually any other country in the world. (The optimal treatment of breast cancer depends on correct staging, on correct genetic testing of the tumor, and on optimizing the individual’s surgical and medical therapies, often employing very new drugs.) In any case, earlier detection of breast cancer is far more likely to be a significant factor in determining outcome in the U.S than it is in recently (or presently) Communist countries with 3rd world healthcare systems.

To be sure, DrRich does not pretend to know anything about the various specific institutions in Russia and China where these studies were conducted. Perhaps they were conducted in those rare showcase institutions that appear here and there under authoritarian regimes, of the sort Michael Moore frequents when he goes to Cuba, and where the level of medical care is said to more nearly approximate medical care in the United States. (Occasional institutions like this will survive even in the U. S. after Healthcare Reform, so that our Congresspersons will have someplace to go.) While this seems very unlikely - could a few showcase hospitals really accommodate the nearly 400,000 women enrolled in these studies? - one must suppose it is possible.

But even if all 400,000 study participants received showcase healthcare, advances in the therapy of breast cancer since the 1990s, when these women were studied, would likely yield different (and better) results today. Does any American oncologist believe that the early detection of breast cancer in 2008 does not improve a woman’s prognosis?

In light of such considerations, why are American doctors apparently so ready to accept the results of the Cochrane review, and to stop recommending breast self-examination? The answer is clear: It is because the data came from RCTs, and since RCTs always yield the truth (you heathen), all other considerations must fall away. Such is the depth of our faith.

DrRich will leave it for another day to discuss the favorable implications to the healthcare system of discouraging breast self-examination (such as having to pay for fewer biopsies), or the lessons that ought to be learned from this example about the advisability of blindly accepting formal guidelines just because they are derived from RCTs, and instead will simply give some friendly advice to the women who might be reading this blog:

First, it is probably a good idea to continue with your breast self-examinations. The downside of doing so is that you may be subjected to a breast biopsy for a benign lump. So take that into consideration. But the upside is that self-examination offers the (proven, according to the RCT data) potential for earlier detection, and therefore offers better odds of long-term survival if cancer is present.

And second, if breast cancer is diagnosed, try to get your therapy in the U.S. rather than in Russia or China. For the average patient in those countries, it would appear that cancer therapy sucks.

Finally, DrRich will close with this plea: Can our guideline writers, at least in the U.S., please refrain from creating new guidelines that are suitable for 3rd world healthcare systems, at least for the year or so it might take for the American healthcare system to actually be reduced to those levels?

Posted in General Rationing Issues | 9 Comments »

More Kudos

June 22nd, 2008 by DrRich

“I know that those of us with chronic diseases can get into our own little worlds of doctors, medications, and treatments specific to our own condition. That makes it harder to step back and take a look at the bigger picture. But I truly recommend that you do, and Fixing American Healthcare is a good place to start. . .

Whether you are concerned about the care about the quality of your own health care, or the status of health care in America — or both — a wonderful first step in your education is reading Dr. Rich Fogoros’ Fixing American Healthcare.”

Read the entire review here.

Posted in Fixing American Healthcare | 1 Comment »

Another Reason To Let the Doctor-Nurses Take the Whole Thing

June 18th, 2008 by DrRich

According to NewScientist Magazine, David Fishbain, Professor of Psychiatry and Behavioral Sciences at the University of Miami, says that up to 1 in 20 patients would like to kill their primary care physicians.*

He learned this interesting tidbit in a survey he conducted among 800 patients undergoing physical rehabilitation or suffering significant pain. He presented his findings at the American Pain Society meetings in Tampa in May.

DrRich, who knows his readers, suspects that several who are physicians and who are unreasonably upbeat or excessively cynical (either personality trait will do) are at this moment thinking, “Sure they want to kill me. But as they’re disabled, their chances of success seem low.”

So chew on this. In a control group of patients not suffering from pain or disability, Fishbain reported that “only” 1 in 50 admitted to having murderous tendencies toward their doctors.

The math is not pretty: the typical primary care physician with a patient load of 3,000 souls can assume that at least 60 of these individuals (up to 150, if he/she treats a lot of patients with pain or disability) would not only like to see them dead, but would be pleased to be the instrument of their demise. (These statistics assume, of course, that everyone who wants to see their doctor lying lifeless in a pool of blood are comfortable admitting this fact to medical researchers doing written surveys.)

We have expended much space on this blog describing how physicians have been maneuvered into covertly rationing healthcare at the bedside, how they have allowed themselves to be limited to 7.5 minutes per patient encounter, and how they have acceded to spending those 7.5 minutes making little marks on a handed-down-from-on-high Pay For Performance checklist (thus leaving little or no time for whatever pressing issues may be on the patient’s own agenda). We have described how, to assuage guilt and to make such behaviors seem less than reprehensible, revered medical organizations have formally amended the code of medical ethics, thus officially wrecking the classic doctor-patient relationship - and committing professional suicide.

The fallout from these developments has landed disproportionately on the PCP, the gatekeeper for the bulk of expensive medical services, whose actions the healthcare system must control at any cost. The loss of PCPs’ professional integrity and their ability to act as autonomous advocates for their patients has done far more than the steady ratcheting down of their pay to make primary care medicine exquisitely unattractive, both to current practitioners and to potential future PCPs. (As per design, says DrRich.) Consequently, this carefully manufactured “PCP shortage” will soon become the medical crisis du jour.

When this crisis is finally ripe for unveiling, the healthcare system will be ready with a solution. Doctor-nurses (the healthcare system fervently hopes) will be more malleable than today’s PCPs, less encumbered by tradition, attitude, and delusions of autonomy, and more likely to follow whatever guidelines the “experts” choose to hand them.

But what about the risk to doctor-nurses from murderous patients?

If the healthcare system is wise enough to create enough of these doctor-nurses, they will be able to relax the 7.5 minute-limit-per-patient-encounter, thus decompressing some of the frustration patients now feel when they leave the doctor’s office, and preventing doctor-nurses from becoming as much a target for patients’ wrath as PCPs apparently are today. To receive that extra time however, doctor-nurses will need to use it wisely, unlike their physician forebears. They will need to spend it engaging in relationship-building and other feel-good activities, instead of (as physicians all too often are wont to do) uncovering new, potentially expensive medical issues that need to be explored.

Doctor-nurses are in the catbird seat, and as long as they follow the script and stick to the guidelines, they’ll be given enough time to keep their patients from hating them.

As for the soon-to-be-obsolete PCPs, DrRich has previously made them some friendly suggestions for salvaging their professional integrity, and he cannot understand why they are not adopting them. Are they waiting for the bullets to fly?

*Thanks to Laura Dolson, Guide to Lowcarb Diets at About.com, for pointing DrRich to this important study.

Posted in Primary Care in America | 7 Comments »

More Fun With Guidelines

May 27th, 2008 by DrRich

Lately DrRich has advanced the proposition that the “Guideline Movement” (the push to reduce all of medical practice to a set of fixed rules by which physician behavior can be controlled) is leading to guideline anarchy (whereby numerous interest groups, from the government to industry to professional societies, have begun a mad dash to create their own sets of guidelines in an attempt to get doctors to behave in ways that will further their own special agendas).

In the effort to give substance - and by extension, some level of legitimacy - to his theory, DrRich gave several examples of anarchical guidelines, and even proposed three different categories of them (i.e., Dueling Guidelines, Predatory Guidelines, and Industry-driven Guidelines).

DrRich is already beginning to see that, once you start looking for them, examples of guideline anarchy begin showing up all over the place. Consider a few of the more interesting ones DrRich has come across just over the couple of weeks:

Dueling Guidelines: Mammograms for women under 50.
DrRich was reminded of this obvious example by a reader. Whether women between 40 - 50 years of age should get routine mammograms has been a point of controversy for some years. Screening these younger women undoubtedly reveals cases of curable breast cancer that otherwise might have been missed. However, such screening also leads to many false positive mammograms, causing unnecessary invasive procedures (and unnecessary anxiety). Because the incidence of breast cancer is lower in younger women, it has been difficult to show objectively that the overall benefits outweigh the negatives of routine mammograms in this age group.

Still, the American Cancer Society, American College of Radiology, and the National Cancer Institute (groups that might benefit by more screening and by finding more cases of potential cancer that need to be evaluated) have long been persuaded that women over 40 should have routine screening. On the other hand, the American College of Physicians and the Canadian Task Force on the Periodic Health Examination (groups that traditionally have relied on overall population-based outcomes, and which are interested in cost savings) say that based on objective evidence, most women should wait until they are 50.

This example is interesting because it shows what happens to dueling guidelines over time. Due largely to vocal and effective lobbying from many groups in favor of screening, professional groups have tended to migrate from the “no” to the “yes” camp. The most recent converts have been the United States Preventive Services Task Force and the American Academy of Family Physicians, groups that traditionally have been in the “cost savings” camp. While the actual data has not changed appreciably, some guidelines have (apparently for non-data-based reasons).

Dueling Guidelines: Fancy anticoagulation for acute coronary syndrome.
A recent editorial appearing in The Lancet points with dismay to two sets of dueling guidelines, one from the American College of Cardiology (ACC) and American Heart Association (AHA), and the other from the European Society of Cardiology (ESC), on the use of two space-age anticoagulation medications in patients with acute coronary syndromes. While the details are fairly mind-numbing and can safely be left alone, the important point is that, after reviewing the same scientific evidence and using the same criteria for rating the evidence, the ACC/AHA essentially said, “yes, use the drugs;” while the ESC said, “no, not so much.” (We may be seeing a trend here, where professional organizations based in the U.S. seem to favor paying for fancy new drugs whose benefit may be considered by more cost-conscious organizations, like those in Europe, as marginal and not worth paying for.)

In any case, it is instructive to hear the lament of the Lancet’s editorialists, who complain,

“The committees reviewed the same research and used nearly identical criteria to rate the strength of the recommendations and to grade the quality of the evidence, but they interpreted the evidence for acute anticoagulant use differently and so reached different conclusions. Therefore, physicians who read recommendations from both the US and European societies might be confused.” (Eikelboom J, Guyatt G and Hirsh J. Guidelines for anticoagulant use in acute coronary syndromes. Lancet 2008; 371: 1559-1561.)

Yes, that’s dueling guidelines for you. If the editorialists would just become regular readers of this blog, they would not find their case so inexplicable.

Premature Guidelines: Beta blockers in noncardiac surgery.
This example requires defining a fourth category of guideline anarchy: Premature Guidelines are guidelines that are promulgated not so much before all the data is in (because all the data will never be in), but rather, before a reasonable amount of data is in. The reason organizations will find it advisable to jump the gun on guidelines is obvious - if you want to get doctors to act in a certain way, and if making guidelines is the best way to do that, the first ones to establish guidelines have a head start on controlling physician behavior.

Our example: Previous (but small) studies have shown that for patients at increased risk for heart disease who are having noncardiac surgery, treatment with beta blockers at the time of surgery reduces the incidence of heart attacks. So, the AHA and ACC (our recurrent friends and aggressive wielders of guidelines) have written formal guidelines that recommend the use of beta blockers in these patients. These particular guidelines, being attractively easy for bureaucrats to track by a simple review of medical records, have been very popular and quite widely adopted as quality measures, performance measures, items on P4P checklists, etc. Accordingly, lots and lots (and lots) of patients have received beta blockers during their noncardiac surgery because of these guidelines over the past several years.

But a very large and well-conducted study (the POISE study) now appearing in The Lancet shows that, while the incidence of heart attack is indeed reduced with the use of beta blockers, the incidence of stroke and of death are significantly increased. The net effect of using beta blockers turns out to be strongly negative. How embarrassing this will be for the AHA, ACC, and thousands of doctors and hospitals who have been dutifully following the guidelines so as to be good medical citizens!

The authors of the study have not played down the inflammatory implications of their new findings. According to theHeart.org, the lead author of the POISE study opines:

“If even only 10% of physicians followed these guidelines — which incidentally in the US are used in quality assessments, where you have people going around ranking hospitals in terms of whether or not they are giving perioperative beta blockers — and if the POISE data are true, then in the past decade 800,000 people would have died prematurely and 500,000 would have had a major stroke perioperatively because we gave beta blockers.”

Oops.

To be fair, an accompanying editorial, written by two physicians partially responsible for the existing guidelines, urges doctors not to panic, and suggests that there’s still a prominent place for beta blockers in these patients, and even suggests (vaguely) what that place might be. They are very reassuring. Unfortunately the data, at the moment, is not. All this will be straightened out over time, of course. But in the meantime we’ve got premature guidelines that remain in force, directing doctors to do something that - by all appearances - is harmful to patients.

(On his About.com heart disease site, DrRich discusses the POISE study, without the sarcasm, for patients who might need to interpret this new information. DB also addresses the implications of the POISE study, here.)

Way-premature Industry-driven Guidelines: Use of IVUS in stent placement.
In a presentation made earlier this month in Barcelona at the EuroPCR meetings, investigators urged that cardiologists use intravascular ultrasound (IVUS) whenever they place stents in coronary arteries. They urge this based on observational data suggesting that using IVUS (an invasive ultrasound technique for visualizing the interior of the artery) can lead to (marginally) improved clinical outcomes. This “suggestion” clearly does not amount to actual “guidelines,” but DrRich includes it here as an interesting view of the type of stuff that can quickly lead to guidelines.

The evidence currently supporting IVUS is not definitive, to say the least. It is based on relatively small observational studies and not on randomized clinical trials. But still, because IVUS is a highly specialized and expensive technique, it is bound to bring a very favorable level of reimbursement to cardiologists, if indeed it were a reimbursable technique. And a very important step to making it reimbursable would be to generate guidelines supporting (or preferably, demanding) its use. And to generate such guidelines, first one must create a groundswell of support among the cardiology thought leaders.

And that’s what was going on at EuroPCR. Indeed, the cardiologist/investigator who is the chief proponent of using IVUS (himself a major shareholder, consultant and speaker for the company that makes IVUS technology), urges that IVUS not be held to “unreasonable” standards such as those requiring randomized clinical trials, but instead that its advantages to patients are so patently obvious that it ought to be made a routine part of stent placement NOW.

Whether this particular example of way-premature industry-based guidelines will ever get anywhere, DrRich obviously cannot say. He offers this example simply as an illustration of the kind of “thinking” that, in the old days, used to lead to fancy dinners, $100 ink pens, trips to Honolulu, and even to compliant female companionship for influential (if geeky) medical thought leaders, all in an effort to increase sales; but that in the modern era leads to guidelines.

Posted in Guidelines, Abuse of | 1 Comment »

Is Guideline Tyranny Causing Guideline Anarchy? (Part II)

May 2nd, 2008 by DrRich

Part I, The Tyranny of Guidelines, can be seen here.

Part II - The Anarchy of Guidelines

Once doctors have been successfully taught that medical guidelines are not really “guidelines” at all, but rather are specific directives with which they must fully comply, it follows that if you are a healthcare group or organization with an agenda, the thing you need to do is to manufacture guidelines that will direct doctors to do whatever it is that most benefits you.

Getting the guidelines to say what you would like them to say is easier to accomplish than one might think. While the practice of guideline-development is ostensibly a highly scientific endeavor that ought not to admit much bias, in truth and to a remarkably large extent it is a political activity.

The more the outcome of a particular guideline-development process is non-deterministic - that is, the more it is capable of being influenced by the personal, political, professional or fiscal agendas of the guideline developers - the more likely it is that you may find competing interest groups devising different sets of guidelines for the same thing. This process, which DrRich believes is only beginning, will eventually create an anarchy of guidelines. Within this anarchy, one can already discern several categories.

Category 1: Dueling Guidelines:

Example: Pharyngitis. Dr. Centor (also affectionately known as DB) is a widely recognized expert on treating pharyngitis, and he has written both on his blog and in the peer-reviewed medical literature on this topic. DB has also written about the many sets of guidelines that have been produced around the world for treating pharyngitis. In regard to 10 sets of guidelines (10!) that were developed by different groups of experts in the United States and Europe, DB notes that the various sets of guidelines show “minimal agreement.” So, for instance, guidelines developed in the United States (where most medical experts receive financial support from industry in one way or another) recommend antibiotics frequently in patients with sore throats, whereas in most sets of guidelines developed in Europe (where keeping costs down is arguably a more important consideration among the medical experts), antibiotics are almost never recommended.

DB further observes that “the 10 guideline groups did not agree on which [medical] articles to include in developing their guideline. More important, these guidelines demonstrate that all guideline committees start with implicit biases. . .The truth about guidelines is that they are molded though the value structure of the panel members.”

Example: Prostate Cancer Screening. DB has also pointed us to this example. The American College of Preventive Medicine (ACPM) concludes that medical evidence to date does not support routine prostate-specific antigen (PSA) screening. This negative opinion on PSA screening is generally supported by the American Academy of Family Physicians and the American College of Physicians. Routine screening, these groups say, may actually produce more harm than good (since false positive PSA levels are common and often lead to unnecessary procedures, and early treatment of prostate cancer often does not translate to improved survival). On the other hand, guidelines from the American Urological Association and the American Cancer Society strongly recommend routine PSA screening, since early detection of prostate cancer clearly saves many lives.

The pattern seen here is readily explainable: General medical practitioners and preventive medicine specialists will tend to give more weight to the overall dollar costs of screening, and to the cost of unnecessary medical procedures that invariably follow from “false positive” screening results. These groups will tend to require strong evidence showing overall benefits to a population before endorsing widespread screening. On the other hand, the groups who get paid to do the screening, or to do the procedures generated by the results of screening, or whose funding is related to the overall incidence of the disease being screened for, will always tend to favor widespread screening.

It is important to note three things here. First, both interest groups are making legitimate points. On one hand, widespread screening will be costlier for society, and may not demonstrate an improvement in overall outcomes across the population. On the other hand, widespread screening will certainly save the lives of many individuals whose cancer will be caught at a treatable stage.

Second, neither group is being completely altruistic here, but instead have produced guidelines that serve their own interests. Specialists who do procedures have a lot to gain by screening policies that generate more procedures. On the other hand, the remuneration for generalists (and preventive medicine specialists) is increasingly tied to cost savings, and to NOT referring too many of their patients to expensive specialists.

Third, both interest groups are comprised of respected experts who use “evidence-based medicine” to reach their conclusions. Everybody in this picture can (and does) passionately support their guidelines as being firmly founded on scientific processes.

Category 2: Predatory Guidelines

Example: Screening of ADHD children. Just last week the American Heart Association (whose physician members tend to be very procedure-oriented - and some might say avaricious - cardiologists) released unsolicited guidelines, recommending the pre-screening of children who have ADHD by a careful cardiac evaluation, including an ECG, before placing them on stimulant medication.

The reason for these new guidelines is that stimulant medication in rare individuals with previously undiagnosed cardiac disease can be dangerous. (So can running on the playground, but nobody is yet recommending cardiac screening before letting kids play.) ADHD today is a very common diagnosis (indeed, it almost seems as if being a boy is now a disease, for which drug therapy is usually required), and routine screening prior to therapy would be extremely expensive both in direct costs, and in the indirect costs related to false positives. Predictably, pediatricians have reacted somewhat skeptically to the AHA’s new guidelines, and the American Academy of Pediatrics (AAP) is asking pediatricians to wait while they scramble to make a formal response.

Members of the AAP recognize, perhaps only subliminally, that the AHA has made a power play here. A powerful interest group with its own agenda has reached onto the AAP’s turf, and has directed AAP member physicians - through the authority of formal guidelines - to change their behavior in a way that may or may not benefit patients, but that will surely benefit members of the AHA. The pediatricians who DrRich knows tend to be kindly, mild-mannered diplomats, in distinct contrast to many of the aggressive cardiologists he knows (and thrives among). So it remains to be seen whether the AAP will respond to this arrogant invasion of their turf with their own set of guidelines. But the non-confrontational idiosyncrasies of pediatricians aside, it is easy to see how “dueling guidelines” could be a natural result of predatory guideline actions like the one taken here by the AHA.

Example: Metabolic Syndrome. In 2005, the American Diabetes Association (ADA) released a stunning statement announcing that metabolic syndrome - to that moment a beloved child of the ADA - does not exist!

Metabolic syndrome is a set of conditions related to insulin resistance that greatly increases the risk of cardiovascular disease. It was initially described by a noted diabetes specialist, and for years remained in the purview of diabetologists. But then, in the late 1990s our friends at the AHA (who seem to be early adopters of predatory guidelines) became very interested in metabolic syndrome, and launched their own guidelines addressing it. Unable to compete with this much larger and much more powerful organization for “ownership” of metabolic syndrome, the ADA finally adopted the unusual tactic of declaring the condition nonexistent. (Those who do not understand why it is important for such organizations to retain ownership of various medical conditions do not understand fund raising.)

Today if you go to the AHA website you will find detailed guidelines on the diagnosis and management of metabolic syndrome. On the ADA website, which used to be loaded with information on metabolic syndrome, all you’ll find is their sad statement saying it doesn’t really exist after all. Patients who formerly had metabolic syndrome are now considered by the ADA to have “pre-diabetes,” which (because this sounds a lot more like a condition they ought to be in charge of rather than a bunch of heart doctors) they hope will place these patients back squarely onto their turf. But thanks largely to the skilled use of predatory guidelines by the AHA (of which DrRich is a proud member), the “metabolic syndrome” terminology has taken deep root in the medical community at large, and is not likely to go away.

Category 3: Industry-driven Guidelines

Industry does not get to create medical guidelines, much to its chagrin, but it has certainly recognized the practical conversion of “guidelines” to “ironclad rules,” and accordingly, is rapidly learning to influence the guideline-development process.

The pathway for doing so looks something like this: a) design a randomized clinical trial that will show that the use of your product substantially improves the outcome of some subset of patients, b) engage key medical thought leaders in the design, management and publication of the trial, c) showcase the results of the trial at major medical meetings, d) petition the guidelines committees of the appropriate medical organizations (aggressively guidelines-oriented organizations, like perhaps the AHA, are especially valued) to incorporate your product into revised guidelines. (If you’ve recruited your medical thought leaders wisely, they will be in a position to influence those guideline committees.)

DrRich may point out examples of this technique in future posts. Suffice for now to say that designing a clinical trial that has a very high probability of showing what you want it to show (step “a” in the process above), is often not particularly difficult. By their nature, randomized clinical trials do not eliminate bias (as many believe), but instead, allow the designers of the trial to control the bias, and thus to tailor the study to yield the desired results. Companies that make medical products figured this out a long time ago.

(The ability to bias the “evidence” is just one of the things that makes “evidence-based medicine” so very intriguing to anyone interested in the nature of objectivity. Or, it goes without saying, to anyone interested in covert rationing.)

Where Will the Anarchy of Guidelines Lead?

DrRich could go on and propose more categories of anarchical guidelines, but this post is already too long, and it is time to get to the point.

Regular readers will already know were DrRich is going with all this. To a healthcare system whose every pore is infused with the need to ration covertly, anything that stirs up anarchy, chaos and confusion can become a great friend. Such things keep doctors (the engines of healthcare spending) completely off balance.

Doctors know they must follow the guidelines or be damned, but when slogging through an anarchy of guidelines, which guidelines should they follow? Somebody, they will eventually plead, needs to bring some kind of order from all this chaos. And of course, a central authority will immediately answer the call, only too ready and willing to put things right.

The overall program, then, looks like this:

1) Make doctors understand that guidelines must be obeyed in every particular. (Done.)

2) Realizing that doctors think this way, various interest groups will begin promulgating numerous guidelines of their own, ultimately leading to “guideline anarchy,” and placing actual practicing physicians into a completely untenable position. (This process is beginning.)

3) Finally, everyone will acknowledge the need for some central authority to step in, sort through the manifold sets of guidelines, and select those (or assemble brand new ones from the parts) that will now become the “official” Guidelines Which Must Be Obeyed. This step is the one that will allow the central authority to select or tailor the guidelines that meet its own special interest (i.e, covert rationing), and to do it in a way that is not overtly heavy-handed, but rather, that rescues order from chaos.

4) Doctors, by this point beaten into submission, will not rail against the externally imposed guidelines, but rather, will be thankful that the central authority has brought wonderful clarity at last.

So once again, covert rationing acts on the system to disrupt its equilibrium; but as always, entropy eventually will become maximized and a new state of equilibrium will be reached. DrRich is no oracle, just a student of thermodynamics.

Posted in Guidelines, Abuse of | 3 Comments »

How Important Is Cholesterol, Really?

January 24th, 2008 by DrRich

In addition to being the Rabble-Rouser-In-Chief for this fine blog and its groundbreaking parent website, DrRich for several years has also been the cardiology expert at About.com. (About.com is a New York Times company, but since his association with About.com predates that of the NYT, DrRich sincerely hopes that his more conservative readers will not hold this against him.) In this capacity, DrRich routinely tries to clarify for his readers (who are mainly patients with heart disease and their loved ones), controversial topics in heart disease. Because cardiologists (like all theologians) never tire of arguing over how many angels can dance on the distal pole of a defibrillation lead, and because the popular media delights in reducing these arcane arguments to breathless (and commonly misleading) headlines, there is a never-ending cascade of material upon which DrRich can draw.

Most recently, the results of a clinical study called ENHANCE has had many in the popular media (in response to new concerns voiced by medical experts), questioning the deeply-entrenched cholesterol paradigm - that is, the idea that LDL cholesterol (the bad kind of cholesterol) is indeed bad, and that anything we can do to lower it is good. Questioning the cholesterol paradigm - a belief system we’ve all been taught since we were babes in arms - is deeply disturbing, confusing and troublesome to many American patients (judging, at least, from the response DrRich has received from readers of his heart disease site).

These patients have been told for years to arrange their lives around the reduction of their cholesterol levels. And while the proportion of people who actually do so does not exceed the proportion who, in earlier times and under a different paradigm, actually arranged their lives so as to further their odds of spending eternity in paradise (modern sinners often preferring instead to rely on today’s equivalent of the deathbed conversion - the stent), the sudden notion that the cholesterol god is dead leaves these patients unbalanced, uncentered and oddly empty. They are also beginning to believe that their doctors, who (some appear to be saying) have been preaching a false doctrine at them for many decades, are even more full of cr*p than previously thought.

In response to this existential crisis, and so as to fulfill his duties to About.com and its parent company, DrRich has posted an article that purports to place all this in perspective, and more importantly, to give patients some guidance as to how to proceed in regard to their cholesterol therapy NOW (i.e., during the next 10 years or so, while the experts debate the issue, and argue over whether the current guidelines - the following of which doctors will continue to be paid-to-perform - actually make sense.)

Normally, DrRich would not trouble readers of the Covert Rationing Blog with topics pertaining to his other duties. But this recent cholesterol controversy has already attracted the attention of other medical bloggers he admires, some of whom have offered (for instance, here and here) very level-headed opinions on the matter. Frankly, while DrRich is clearly very comfortable pontificating on matters related to healthcare reform (and most other topics), he gets nervous touching on theology or its close relative, cholesterology. So DrRich will be very interested to know from readers of this blog if his advice - which, again, is aimed at American patients - seems sufficiently clear, and most of all, reasonable. The posting can be found here.

Thank you for your indulgence.

Posted in Cardiology Topics | 3 Comments »