Truth will out -- if you let it

Most of the important political debates going on this country right now have something important in common -- there happens to be truth on one side or the other and we could just do the necessary experiment to prove it.

Republicans are screaming and yelling about a "government takeover" of health care and how they're going to confiscate your money to take care of the shiftless and then let you die. Well, there's an easy way to settle the question. All the Democrats have to do is pass a decent bill and then soon enough we'll all know who was right. And they wouldn't be taking much of a chance -- as we all know they really did have a government takeover of health care in the UK, and that country is now a totalitarian dungeon where the enslaved people live longer and healthier lives than we do, pay half as much for health care, and are forced to eat their french fries off of old newspapers. In Canada, they had a government takeover of health insurance, but not health care, and the enslaved population is forced to live longer and healthier than us, to pay about 2/3 as much for health care as we do, and to continually dodge flying hockey pucks.

In Switzerland, they regulate insurance products -- which is actually similar to the commie death panel legislation we are actually talking about -- and the slaves are forced to live longer and healthier lives, to pay just slightly less for health care than us, and to blow giant wooden trumpets. So the worst that can happen, it seems to me, is that we end up like the Swiss, and how is that going to be bad for Democratic political prospects? Unless, of course, they don't pass the legislation, in which case the Republicans will be able to continue to claim that they were right. So what do you think will happen?

Same with same sex marriage. It happened here in the People's Republic of Massachusetts, and so far, no fire and brimstone. In fact we have an unusually low divorce rate and only a normal level of fabulousness. So all you have to do is try it!

Climate change, I'm sorry to say, works in the opposite way. If we continue to do nothing, we'll know soon enough what the consequences will be.

I got an excuse

Sorry for no post yesterday, I had to finish both a paper and a conference abstract. It's hard work -- sometimes even harder than watching war on TV. And I also heard a talk by Michael Drummond, DPhil, who is the chairman of a death panel.

At least that's how he introduced himself. He's the chair of one of four committees of the UK's National Institute for Health and Clinical Excellence, abbreviated NICE because the H would just mess it up, and he was here to give us all the latest on how NICE works and the politics of death panelling in the land of bangers and mash.

The only way we're going to get health care in this country that serves everybody well and fairly is if we develop some kind of equivalent to NICE. As long as we have multiple payers, it's going to be difficult, but it's not impossible with a sufficiently strong regulation. There are a lot of moving parts in this discussion so I refer you to my series beginning December 14 and concluding on January 5 if you need to a primer. So today I'll just talk about NICE.

Drugs and medical devices get licensed in the UK pretty much on the same basis they do here: they have to show reasonable evidence of being safe and effective, but not necessarily more effective or more safe than existing and probably cheaper alternatives. So Dr. Drummond and his fellow death panelists decide in a separate step whether the National Health Service will pay for them. They can rule that a drug can be used freely as per license; used only in specific circumstances; or not used routinely meaning that a physician would have to ask special permission to have it paid for. Note that the license means the doctor can prescribe it, it's just that you will have to pay for it out of your inheritance.

The hard part is that these decisions are about what the NHS will pay for and that means cost is part of the calculation. Before we get to cost, of course, we have to measure benefit, and NICE uses Quality Adjusted Life Years, with further discussion here. This way of looking at things seems a bit odd to Americans whose values seem to include infinite entitlement. It's not just the obvious consequence that NHS won't spend 100,000 pounds to extend your life by one month.

Dr. Drummond's panel considered the application by Glaxo to approve zanamivir (Relenza) for the flu. It's not very expensive. But they turned it down. Glaxo's application just said that the benefit was that, if taken within 48 hours of the onset of symptoms, it shortened the average duration of symptoms from 6 days to 5. Dr. Drummond said, "What's the benefit of that? When I have the flu, once I start feeling better, my wife starts asking me to do things around the house." That's just not enough of a clinical benefit for the NHS to pay for it at almost any price, because the QALY's it buys you are infinitesimal. One day of not having the tail-end symptoms of a bout with the flu just doesn't compute. In order for Glaxo to get it approved, they had to go back to the drawing board and try to show that it reduces the risk of severe complications, hospitalization or death in high risk people or makes a big difference after severe complications have developed. (So far, I believe, they haven't done that.) In the mean time, it's licensed in the UK, if any of Her Majesty's subjects want to buy it themselves, they are free to do so with a doctor's prescription, but Her Majesty's exchequer won't pay for it.

How that is contrary to freedom I do not know, but Sarah Palin says it is.

Next: How NICE operates.

Risk assessment

We are having a rain event here in Boston. Were it a snow event, the hair hatted newsbots would be proclaiming Armageddon. It's been bad for a long time, but in recent years they have actually ramped up their obsession with inclement weather, which I would not have thought possible. An inch of snow is enough for them to devote the entire local newscast to it -- of course there is nothing to say so they send some clown to stand on an eroding barrier beach, with no hat of course because he wouldn't want to waste his $100 coif, and announce with the snow piling up on his ears that there are waves and the eroding barrier beach might be eroding some more. The resulting mass hysteria has the sheeple clogging the supermarket parking lot with SUVs while they strip the shelves of milk and bread. It is idiotic beyond all understanding.

Anyway, back on topic. The FDA issued two alerts today, one concerning the diabetes drug Avandia, the other concerning two HIV drugs, saquinavir and ritonavir, which are often prescribed together.

Avandia has been in the news lately, with a Senate report alleging that the manufacturer Glaxo failed to inform the FDA of everything it new about cardiac risks associated with the drug. For the record, Glaxo denies the charge and says the facts are not all in yet on the risks of Avandia as a major trial is still underway. The FDA release only says yeah, we're waiting on results of the ongoing RECORD trial and we'll talk about it all in July.

I'm not going to predict how all this will turn out, but it does add more weight to the proposition that most new drugs should not get an "all or nothing" approval. In a case like Avandia, where there are alternatives available, it might make more sense to give a preliminary approval, which would allow only relatively small scale marketing with surveillance of patients who receive the drug, to get stronger reassurance that there are no long term safety issues that wouldn't have shown up in the original clinical trials. Critics assert that Avandia causes 500 heart attacks and 300 heart failures monthly. This may or may not turn out to be true but it's a chance we didn't have to take if we had a policy of gradual and conditional new drug approval under ordinary circumstances.

The saquinavir and ritonavir issue is a little different. These are so-called protease inhibitors and yes, they do have side effects, potentially serious ones, but they also do an excellent job of suppressing HIV replication in conjunction with one or more other classes of drugs and that's worth putting up with some risks. There are many patients who absolutely need them. When people face serious and ultimately life threatening illness and they don't have better alternatives, then a more expedited path to widespread use makes sense. (The new problem that has been discovered, as it turns out, is somewhat speculative and only effects some patients who are at risk for cardiac arrest.) It seems to me that these are distinctions we ought to be able to make even though. It would slow down some drug company profits but it would make more sense from a population health point of view.

There's got to be a better way

As long-time readers know, I'm definitely concerned about loss of topsoil and agricultural runoff but I'm uncomfortable with no-till agriculture because it requires heavy use of herbicides. We're often told that herbicides in common use in the U.S. are safe but new information about one of the most widely used, atrazine, is disturbing. U.S. farmers use 34 million kilograms of the stuff every year.

It's been considered safe but it turns out that the studies on which that conclusion has been based are, you guessed it, largely funded by the pesticide industry and even conducted by scientists employed by the industry. Atrazine is found in drinking water in the U.S. It is now emerging that it is an endocrine disruptor that affects the sexual development of amphibians, fish and mammals.

Robust data suggestive of hormonal effects, including partial gender reassignment, come from amphibians and fish. And a review in the January Environmental Health Perspectives by Jason Rohr and Krista McCoy of the University of South Florida in Tampa includes more than a dozen papers out since atrazine’s last regulatory review. The EHP review highlights a long list of reproductive and developmental impacts in these animals. . . .

Previous EPA analyses of atrazine safety had access to four earlier reviews of animal data, Rohr notes — all funded at least in part by industry. He maintains that his is the first review that is free of industry involvement. Funding for his assessment came from the EPA, the National Science Foundation and the U.S. Department of Agriculture.

There are suggestions from epidemiological studies that atrazine may be causing birth defects in humans. We could ban atrazine -- I'm not holding my breath -- but I don't have a great deal of confidence in alternatives either. Glyphosate (Roundup©), one of the most widely used, is sold by Monsanto in conjunction with genetically modified seeds that are resistant. It's considered very safe but as usual, industry funding is largely behind that belief. It's often used with a surfactant which is toxic to fish and amphibian larvae. Since the surfactant is not considered an "active ingredient," it is unregulated. There is a great deal of evidence of toxicity of Roundup in mammals, including humans, but again, it may be the formulation, not the glyphosate per se, that does the damage. It doesn't matter, it's Roundup, not pure glyphosate, that's being sprayed all over the earth. (The Wikipedia article is as good a source as any on all this. We've known it forever -- I wrote a report that contained all this information when I was in graduate school in environmental policy in the 1980s.)

All this strikes me as nuts. I am going to continue to control weeds by tilling and mulching. Unfortunately, for large scale agriculture, that's very difficult and right now, we can't feed the world without resorting to these unpleasant alternatives.

Anything for a buck

It's bad enough, I suppose, that you can market any eye of newt and toe of frog without FDA approval, until and unless people start dropping dead from it, but the same applies to medical devices. Here's an FDA notice that may make you incredulous:

FDA is notifying consumers and healthcare providers of its warning not to use ear candles - a hollow cone about 10 inches long made from a fabric tube soaked in beeswax, paraffin or a mixture of the two - because they can cause serious injuries, even when used according to the manufacturer’s directions. According to advertised claims, a burning ear candle draws ear wax and “impurities” or “toxins” out of the ear canal. Other claims for ear candles include relief from sinus and ear infections, headache and earache, as well as improved hearing, “blood purification,” improvements in brain function, and cure cancer. FDA has found no valid scientific evidence to support the safety or effectiveness of these devices for any medical claims or benefits. FDA has received reports of burns, perforated eardrums and blockage of the ear canal which required outpatient surgery from the use of ear candles.

FDA is especially concerned because some ear candles are being advertised for use in children. Children of any age, including babies, are likely at increased risk for injuries and complications if they are exposed to ear candles. Small children and infants may move during the use of the device, increasing the likelihood of wax burns and ear candle wax plugging up the ear canal. Also, their smaller ear canal size may make children more susceptible than adults to injuries.

Ear candles are sold and promoted in a variety of locations, including health food stores, flea markets, health spas and salons, as well as on commercial web sites.

Note, however, that they cannot stop this insane product from being marketed. All they can do is issue a warning, which hardly anybody will see. But you know, we don't want that Nanny state interfering with our God given right to be defrauded.

Vengeance

I suppose I ought to weigh in on the Amy Bishop thing given my deep personal connection, i.e. I live in Boston whence she cometh, I am in a vaguely related corner of academia and I know some Harvard-trained biologists. This post offers no particular expertise nor profundity, so don't bother reading it.

Let us first note that the word "justice" has various meanings and much discourse is confused because people conflate them.

There essentially four justifications for criminal justice:

A) Retribution. You hurt me, I want to hurt you. The criminal justice system institutionalizes this human impulse. Presumably carrying it out through a ritualized process with formal rules and constraints is an improvement over personal vendettas and family feuds. It strives for some degree of proportionality, and it stops the process before a cycle of retaliation develops. It is also argued that it provides victims with assurance that society respects their injury and is purported to give them consolation.

B) Incapacitation of dangerous people. Lock them away or kill them so they can't do it again. This presumes that a history of transgression is necessarily a good predictor of future behavior. Since most people are incarcerated only temporarily, in most cases it also only makes sense if (C) also pertains --

C) Rehabilitation. Prison was at one time envisioned as an opportunity for sinners to reflect and repent. At one time and place or another in the U.S., prisoners have also been offered addiction treatment, other forms of counseling, vocational education and other services to improve their chances of achieving a law abiding life upon release. For the most part, nowadays, we do very little of that and prison just makes people angrier and more dysfunctional.

D) Deterrence. Don't do the crime if you can't do the time.

Now, there are some people who think we should not indulge in (A). A well-known example was the radical Jesus of Nazareth, who was notoriously soft on crime with the exception of the financial services industry. It is on this question, obviously, that much of the debate over the death penalty pertains.

But the issue with Prof. Bishop is more specifically the insanity defense. Her lawyer, grasping for the only chance to keep her from the needle, says he suffers from paranoid schizophrenia. I am not going anywhere near armchair diagnosis. I will simply say that she obviously has more than one screw loose.

The interesting question is why we think that having some particular screw or set of screws loose, and not others, absolves people from retribution. Basically, if you can convince a judge or failing that a jury that a person's invisible mental state had certain properties at the time they committed the illegal act -- and not necessarily before, after, or right now -- (A) does not apply and the entire problem gets kicked down to (B) through (D); whereupon we discover that (D) doesn't really apply either since the person had to not know right from wrong or have been unable to conform his or her conduct to the requirements of the law. Presumably such a person would be non-deterrable. So, lock 'em up to achieve (B). In some circumstances in some jurisdictions, you also try to fix 'em -- (C) -- meaning you put them in a purportedly mind-fixing institution rather than a prison, but not necessarily. (John Hinckley is in a mental hospital; Ted Kaczynski is in a federal super-max prison.)

So what do I make of this? I think it's absurd. The distinction between a person who is able or unable to conform to the law is meaningless. If they didn't do it, then a fortiori they were unable to do it. The reason this statement seems strange to most people is because we have a distorted metaphysics. Amy Bishop is not the cause of whatever is strange about her that resulted in her atrocious behavior; rather, this happened to her.

The only reason we make people the ultimate agents of their own nature is because we don't know any better. If we can find a brain tumor or a head injury, we're perfectly willing to say, "Aha! John isn't responsible, it's this awful thing that happened to him." But in most cases we just don't know how people got to be the way they are -- the brain develops through an incomprehensibly complex dance between genetic inheritance and environmental happenstance. If a person seems sufficiently weird in just the right ways, we might apply a disease label. This psychiatric labeling is largely arbitrary, despite the claims of the DSM mafia to "scientific" justification. Having a disease label offers offenders some degree of exoneration in general perception, though not necessarily in the law. If their weirdness doesn't happen to be just right, they don't get the label and they are stuck with responsibility for whatever they happen to be.

This makes no sense whatsoever. A straightforward example is the the concept of "mental retardation" as exculpation. If your measured IQ is 70, you're retarded and you can't be executed. If it's 71, you're just not very bright, and that's no excuse.

Whatever else you can say about Amy Bishop, she's clearly nuts. How do I know this? She shot 6 people at a faculty meeting.

I get e-mails

It's one of the perks of blogging. I'm going to reproduce this one in its entirety.

Recently, congress introduced the “Dietary Supplement Safety Act of 2-10,” which, if passed, will drive up the cost of dietary supplements and restrict access to them. The bill will place added costs through tax dollars on relatively low-priced, scientifically proven, dietary nutritional supplements (please find full details in the press release below).

In a time when Americans are seeking more alternative, preventative healthcare solutions instead of relying on expensive drugs, this bill not only threatens businesses that manufacture supplement products but the American consumer who is now seeking ways to improve health before they spending money on doctors visits and prescriptions.

Organizations such as the Life Extension Foundation manufacture highly effective nutritional supplements under strict pharmaceutical grade, FDA standards and are marketed under some of the most stringent restrictions placed on any products sold anywhere in the world.

I would be delighted to have you speak with Stephen Joyal, M.D., Vice President of Scientific and Medical Affairs at the Life Extension Foundation. Dr. Joyal is a genuine expert who can provide insight and comments from the perspective of the medical professional and from the nutritional supplement maker. I know you will find the facts he reveals to be fascinating and eye-opening. Please e-mail me or call me at 212-966-0024 and I will be glad to arrange for you to speak with Dr. Joyal.

Best,

Ashley

Okay, now would you like to hear the truth? Thanks to some friends in Congress such as Sen. Harkin, by labeling their snake oil "supplements" the manufacturers in fact do not have to produce any data whatsoever that the junk is effective in the slightest, let alone "highly effective." The crap sold in the GNC and Whole Foods and even the CVS is not "scientifically proven," it does not constitute "preventative healthcare solutions" and no, it won't extend your life. All it will do is empty your wallet. The only opportunity the FDA has to intervene in this large-scale fraud operation is if a product is discovered to be dangerous; and since they don't have to test any of it ahead of time to find out whether it is or not, that only happens when people start dropping dead in large numbers, as in fact happened with products containing ephedrine.

It's long past time we put these con artists out of business.

Statement of Eldrick "Tiger" Woods

I happen to be highly skilled at hitting a little ball with an elaborately engineered stick and making it go where I want it to. People like to watch me do this on TV, so I get a lot of big money prizes for doing it. I make even more money because corporations paid me to be in their ads on the theory that it would cause you to witlessly associate their products with wealth, fame, and a good golf game, thereby causing you to buy Rolexes and Buicks. Consequently, I accumulated a billion dollars, of which I spent 50 or 60 thousand a month to keep women of easy virtue on retainer to satisfy my soulless hypersexuality. Why would you even give a shit? It has nothing to do with golf. I can afford it. My wife isn't happy about it but that's between her and me. What's the matter with you people anyway? Get a life. Sheesh.

The Nuclear Option

At least we aren't saying "nukular" any more, but now that the President (and at least we aren't saying Preznit any more either) is seriously annoying yet another category of his supporters, this time by pushing nuclear power, YT is compelled to weigh in if for no other reason than some personal history. As a youth, I was involved in organizing this demonstration, which filled the mall in front of the Capitol with people as far as the eye could see; and this conference. (Until I tried it, I didn't know that you could find scanned newspaper articles from before the Internet era. Now y'know.) I still have one of those frightfully ugly "Nuclear Power? No thanks!" silk screened posters in a storeroom.

What I have to say about all this today is that it's complicated. The main driver of public opposition to nuclear power has always been safety concerns. The Three Mile Island meltdown happened between the conference and the march, IIRC, and it scared the hell out of people, even though as it turned out the amount of radiation that escaped from the site was not really significant. Then the Chernobyl meltdown happened and that certainly was a huge economic and public health disaster. But the truth is that the Chernobyl design had nothing to do with the kinds of reactors that we have here in the U.S., and modern designs would not allow for a repeat of the TMI event.

The safety of nuclear power plant operation is something of an imponderable -- how do you value a high impact, very low probability event? However, we know that coal fired power kills lots and lots of people all the time, from coal miners to people who breathe, not to mention animals, acidifies waterways, deposits mercury in the ocean, and is responsible for a whole lot of CO2 emissions as well.

The more credible objections to developing nuclear power are more complicated. The first you undoubtedly know about. Standard light water reactors, famously, produce spent fuel that is highly radioactive, remains dangerous for thousands of years, can be used by terrorists to make "dirty bombs" and conceivably used to extract plutonium for nuclear weapons. The solutions to these problems, such as they are, have obvious side effects. Nobody wants a permanent spent fuel repository nearby. Whether that's necessarily entirely rational or not, it's a fact. Nobody wants large amounts of high level nuclear waste going by on the highway or railroad. Again, you could invest any arbitrary amount to get to any arbitrarily defined level of safety, but there are still people who wouldn't like it. For security reasons, you'd probably have to keep it a secret when and where the shipments were moving, and you'd need a lot of sullen men with guns guarding everything.

Right now, the way we deal with these problems is by keeping the waste at the power plants where they are generated. It does settle down after a few years and become somewhat less dangerous, but that plutonium hangs around forever by the standards of historical time. And if we keep generating more and more and more of it the whole scenario just gets uglier. Proponents of nuclear power just ask us to weigh these problems against the continued generation of CO2 and the other environmental and social problems associated with fossil fuels. It's not actually insane to argue about that balance, it seems to me. Honorable people may disagree.

(There is a speculative proposal for a new technology, called a "traveling wave" reactor, which produces far less waste over time by effectively burning up the hot isotopes produced by the initial fission reaction, and which can be fueled with unenriched uranium. Bill Gates is a big fan and investor, but we don't know if it will ever work. These reactors use liquid sodium, rather than water, as a moderator, which also gives one pause. But Obama is supporting development of conventional light water reactors right now.)

But then we come to the economics of nuclear power. Nuclear power plants are far more costly to build than conventional power plants -- we're talking many billions of dollars. That means they suck up a lot of investment capital that could go to other uses. In order to pay back their investors, they have to run for a long time, and not be off-line very often for repairs. Another TMI type incident, even if nobody is injured, would be an economic catastrophe. As it turns out, investors aren't willing to go there, which means nuclear power can't move forward without government loan guarantees and insurance subsidies. Obama is proposing to offer precisely that. So where it the outcry from the Cato Institute and the rest of the libertarians and "free market" fundamentalists?

What is more, the truly vast investment needed to build enough nuclear power plants to make a meaningful contribution to our long-term needs would drive out all sorts of other investments we desperately need to make, and wouldn't give us any payback at all for decades, if then. It would concentrate political and economic power in the hands of enormous corporations that could hold their regulators hostage.

And oh yeah -- it would require enormous amounts of fossil fuels to construct all those reactors.

It is these economic, social and political impacts that really concern the more thoughtful foes of nuclear power. Ownership of wind and solar power can be far less centralized, even personal; these sources can be built incrementally; they don't create security issues; when they reach the end of their useful lives they are innocuous and recyclable. On the other hand, realistically, with current technology, they aren't going to make a major contribution to meeting our needs any time soon. For one thing, we don't have an electrical grid infrastructure that can deal with intermittent sources and we don't have a good way of storing power. So a large capital investment is needed for that, although it could be publicly controlled and so less of a political danger.

The fact is there is no easy way out of our problems and not so good solutions may be necessary. That's evidently what the president thinks. How about you?

Update: A commenter links to a Cato writer who is indeed intellectually consistent on this and decries the subsidies. Good on 'em. Now let's see if any more real conservatives show up to make noise publicly along these lines -- most people think Obama is doing this to appease Republicans.

Uhh, no, you can't do that

Whatever you may think about the morality of assisted suicide in cases of terminal illness, this is not allowed and cannot be allowed. Ray Gosling says his friend was dying of AIDS -- this was before they had effective treatments -- so he asked the doctor to leave the room and smothered the guy with a pillow. Let us assume the smotheree requested smothering -- which Gosling actually does not make clear, but let's stipulate it. Anybody could go into a hospital room, kill the inhabitant, and then just claim they had asked for it.

Not a defense. Gosling says on television that he committed murder.

Oddly, Richard B. Cheney says on national TV that he is a war criminal and there are no repercussions.

We've all had difficult colleagues but Amy Bishop is an outlier. But we all know what's really weird about her story. How many poor Black or Hispanic kids could blow away a family member with a shotgun, then run out of the house and attempt serial carjacking at gunpoint, and have the police and the DA just drop the whole thing as an unfortunate accident without even investigating?

Just think about it when you contemplate the composition of the prison population.

Well, something is going on

The disorder -- or far more likely multiple disorders -- labeled as autism are much in the news and of blogospheric concern mostly because of the increasingly pathological cult that blames it all on vaccination; and also because of the epidemic of fraudulent treatments. Rather than reviewing all this crap or giving you a collection of links I will simply refer you to Orac who has been all over this like hot sauce on a chicken wing for as long as I've been cyberspacial.

However, just because the issue is infested with destructive bullshit doesn't mean it isn't a real problem for a lot of children and families. A serious underlying difficulty that has helped create room for the snake oil salesman has been a lack of sound epidemiological data. Indeed, as with all collections of symptoms for which we have no etiological explanation, even defining autism and applying the label is problematic. The presence of autism in an individual child, and by extension the prevalence in the population, essentially comes down to whether someone with the appropriate credentials has applied the label. It is this ontological problem which has allowed people to claim there is a growing epidemic of autism, and allowed self-promoting serial liars like RFK Jr. to claim it is temporally associated with whatever causal factor they want to blame.

Since 2000, CDC has been trying to bring at least a semblance of order to the epidemiology of autism through a project called the Autism and Developmental Disabilities Monitoring Network. Here is their latest report. Unfortunately, it doesn't really succeed in reifying the nature of autism. What they do is to collect all the developmental evaluations of children they can get their hands on in certain states or areas, and then have credentialed people review them according to standard criteria. They don't depend on children actually getting a diagnosis of autism in the community -- they can undiagnose an (anonymous) kid who has the label, or diagnose one who doesn't. In some places they have access to medical records only, in others to school-based assessments as well.

Because a lot depends on whether a child ever undergoes such an assessment in the first place, they can't come close to eliminating the problems of ascertainment bias that affect both changes over time, and disparities among demographic sectors. What they can do, however, is put a floor under the prevalence, and the bottom line is it's quite a bit higher than we used to think. It ranges widely from place to place, probably although not necessarily entirely due to differences in the likelihood of ascertainment. Nevertheless, it's worth announcing that they find the overall prevalence to be 9/1,000; it is much higher for boys -- 1 in 70, compared to 1 out of 315 girls. This is most certainly an understatement, since the ascertainment problem, given their consistent criteria, can only result in an underestimate. In other words, there is a screen in that children have to undergo a professional assessment that results in an interpretable record. Not surprisingly, the measured prevalence is lower where only medical, and not educational records are available. Still, the prevalence as ascertained through the network continues to increase over time.

Contrary to the prevailing stereotypes, which are based largely on dramatically interesting accounts of very high functioning individuals with the Asperger's label, the majority of children found to have autism spectrum disorders through the CDC network have low measured IQs. But early diagnosis and appropriate intervention really matters -- as this study shows. Unfortunately, in the CDC surveillance network, most children are identified late, after four years of age.

The fact is, we have absolutely no good idea of what causes the array of developmental delays which get the catch-all label of autistic spectrum disorder. It undoubtedly has to do with genetic predisposition interacting with unknown environmental factors -- which undoubtedly do not include vaccination or "refrigerator" mothers, or exposure to mercury. We just do not know. It is understandable that parents will seize on whatever explanation is offered, but they really, really need to resist that temptation. We do not have the explanation. But we can do something about it, particularly in the less severe cases.

But these prevalence numbers tell us we have a huge loss of human potential, and it truly does mandate urgency in figuring out what's going on. I want affected families to know that the reason we attack the anti-vax cultists and other quacks is because we care. We really do.

In spite of Your Wondrous Intertubes . . .

the New York Times is still around, and still often worth your while in spite of its descents into Judith Millerhood, the Whitewater Hoax, and many another sin. Today's issue I particularly commend to your attention. Somebody in the corporate media finally gets around to actually trying to find out what the whole Tea Party thing is all about, with this lengthy venture into cultural anthropology by David Barstow. Bottom line: it's pretty much the same old Patriot Militia/John Birch Society wackiness that's been around forever, but the new phenomenon is that a lot of people who have suddenly been wiped out economically and need some sort of an explanation for what's happened to them and somebody to blame have suddenly latched onto it, often with a push from Glenn Beck.

That may not be a big surprise to you but it is a bit disconcerting to read how radicalized and violently alienated a whole lot of previously very ordinary, apolitical people have become. Hard times. It is very helpful that on the same day, Michiko Kakutani reviews David Aaronovitch's Voodo Histories. Still mystified by the whole thing? Aaronovitch makes the glass so clear, it seems to disappear, as summarized by Kakutani. "[O]verarching theories [i.e., conspiracy theories that blame shadowy elites] tend to be “formulated by the politically defeated and taken up by the socially defeated, ”losers 'left behind by modernity.'” Quoting Aaronovich:

If it can be proved that there has been a conspiracy, which has transformed politics and society, then their defeat is not the product of their own inherent weakness or unpopularity, let alone their mistakes; it is due to the almost demonic ruthlessness of their enemy.

The great tragedy and disgrace, of course, is that progressives have utterly failed to address these people -- to acknowledge the profound pain out there in the country, to explain its source, and to commit themselves to a program to heal it. When the blithering idiot Sarah Palin asks, "How's that Hopey Changey thing working out for you?" she has an excellent point. So far it isn't working out for people at all, and Obama and the congressional Democrats aren't talking to them. Glenn Beck is. Why? I have a conspiracy theory about that . . .

The Age of Denialism

Religion is not such a mysterious phenomenon -- it is deeply embedded in the world's cultures, from that long span of millennia when we just didn't have any better explanations. We grow up believing what our parents teach us, and religious belief is often the most powerfully indoctrinated kind of belief. Religion also gets a boost because it meets certain psychological and perhaps social needs of some people.

But the other forms of anti-rationality that seem to be rampant today are harder to explain. Sure, in some cases there are well-moneyed interests that expend substantial resources promoting nonsense -- from homeopathy to climate change denialism and the anti-vaccine movement that wants to sell you bogus "immune system boosters" and treatments for autism. On the other hand, the financial interest behind AIDS denialism doesn't amount to much more than Mathias Rust and his vitamin pills.

Even so, financial backing doesn't really explain the attraction for many otherwise smart and sane people who, after all, have the opportunity to learn the science and make up their own minds, but seem to find something liberating or empowering about slurping up the Kool Aid. The fact is a rift has developed between the institution of science and a large chunk of the public. Scientists practice in exclusionary settings, speak their own languages, and generally think it is demeaning or compromising to try to communicate with lay people. And indeed, that can be a good way to damage your chances for tenure. Many a scholar has been driven into the wilderness for writing popular books (viz. Paul Starr).

In the area of health and medicine where I happen to know something, anti-science movements kill people flat out. For example -- and it's only an example -- Peter Duesberg, the father of AIDS denialism, is personally responsible for the deaths of at least a third of a million people, and probably many times that number. Mark Hoofnagle says that:

Denialism is the employment of rhetorical tactics to give the appearance of argument or legitimate debate, when in actuality there is none. These false arguments are used when one has few or no facts to support one's viewpoint against a scientific consensus or against overwhelming evidence to the contrary. They are effective in distracting from actual useful debate using emotionally appealing, but ultimately empty and illogical assertions.

He feels it is defined by tactics rather than by content: "conspiracy, selectivity (cherry-picking), fake experts, impossible expectations (also known as moving goalposts), and general fallacies of logic."

All well and good, but it still doesn't answer the question: why? Scientists may be aloof and esoteric and all that, but why do people affirmatively prefer to believe in nonsense? I just don't see anybody with a convincing answer to that question.

12 February 1809 – 19 April 1882

That is of course Charles Darwin, born 201 years ago today. There isn't much of a mite I can add to the commemorations and analyses, but I might as well make a personal statement.

Many people maintain that it is more important to convince people of the truth of our origins than to disabuse them of their religious delusions, so it is best to pretend that there is no conflict between science and religion, that they simply address different spheres of meaning or address different questions. I find that disingenuous if not downright dishonest.

Once you accept that humans are the product of a process that may have occurred over nearly 4 billion years, in which purely stochastic events were shaped by indifferent forces into increasing complexity which could have led to infinitely many different outcomes but just happened to produce us, you are forced to a philosophical position which is incompatible with every theistic system I know of. This conclusion is only reinforced by our discovery of the universe of hundreds of billions of galaxies.

Religions insist that we are uniquely important to a vast, sentient power whose scope and domain is that of the entire universe; and that power is the source of meaning, human purpose, and morality. Plainly, in the world of Darwin and Hubble, that cannot be so. The source of meaning, human purpose, and morality, is us -- humans -- as we happen to be.

That is a very humble position. It is the religious who are arrogant, by insisting that we have a special place in the universe. We don't. We are what we are, which is nothing to anything or anybody but each other. To me, that is plenty.

If anyone wishes to disagree, please bring it on.

That, err, thing we don't want to talk about

There are two essays in the new NEJM about end of life care, from Robert Truog, M.D., and Lisa Rosenbaum, M.D. Unfortunately they are subscription only, and they are both very personal so I feel it would be improper for me to try to represent them in detail here. But they are representative of a trend I have noticed lately -- this open access essay in Health Affairs, again very personal, being another example -- toward push-back against what writers see as too-ready acceptance of futility.

Dr. Rosenbaum's grandmother, with advanced dementia, wound up through what was essentially a series of misadventures getting taken to the ER, despite DNR and Do Not Intubate orders, when she suffered some sort of a neurological crisis. She ended up living for another year in a world of delusion, though generally alert, able to speak and feed herself. Dr. Truog performed aggressive efforts at resuscitation on a 2 year old boy with severe brain damage, who was in fact already dead and which he knew to be absolutely futile, solely to please the family, a decision he does not regret.

I believe it is important to acknowledge and respect these points of view because there is a danger that the current debate over these issues will be misconstrued. I take it back -- it is, obviously, being misconstrued. Whatever decisions you feel you would make for yourself and your loved ones, the only people who are suggesting imposing the decisions they would make on others are the people who think you should not have the right to accept death when there is no meaningful life. In other words, counseling about end of life care is just that, counseling, to help people make decisions that are right for them. Medicare will still pay for whatever choices you make.

The exception in most hospitals - and this is not a question of insurance or federal policy, it's a question of medical ethics - is that physicians are not required to attempt resuscitation when they know it will be futile, as Dr. Truog did. This has a trivial cost, which is really not a consideration. The outcome was that the child was dead, as he would have been anyway, but his body was battered and bruised from the effort -- a fact which actually pleased the parents.

In my own father's case, as his dementia advanced and he lost the power of speech, no longer recognized family members, and could no longer feed himself, my mother decided on her directives. My father's primary care physician, I'm sorry to say, was no help to her in this, but she had the advantage of being able to consult with her son who has direct access to physicians who think about these questions deeply. She ordered that under no circumstances should he receive IV antibiotics, or a feeding tube, or be hospitalized. He died peacefully in a nursing home, when nature took its course. However, if my mother had decided he should be hospitalized, intubated and saturated with antibiotics, Medicare would have paid for it.

The issue is not to change that policy, it is to give people the right to choose and the information and support they need to do so. Will we ever calm down enough to make these distinctions and talk about them in a civil manner? Not of the Republican Party can help it.

Do you believe in the ontological status . . .

of psychiatric diagnoses? (Or not.) Do you want to put your own 2 cents in?

Have at it. The draft of the DSM-5 is now open for public comment. And by the way, it matters to you, because chances are, you are now or will be officially mentally ill. Yep, we're all nuts.

One of the goals of the APA with the new DSM is avowedly to cut down on the prevalence of psychiatric disorders:

The psychiatric group expects that overarching change could actually lower the numbers of people thought to suffer from mental disorders. "Is someone really a patient, or just meets some criteria like trouble sleeping?" APA President Dr. Alan Schatzberg, a Stanford University psychiatry professor, told The Associated Press. "It's really important for us as a field to try not to overdiagnose."

Yeah right. That's why they have added even more diagnoses. Yes, they've consolidated a few to make it look like fewer, but that's a cheap trick. For example, they've decided to conflate Asperger's Syndrome with autism -- which strikes me as completely backwards. There is no reason to believe these are somehow the same entity. The basic reason why a diagnosis is psychiatric rather than neurological is because they don't know the etiology. As soon as a disease is actually understood, it ceases to be psychiatric. So keep that in mind as you comment.

Oh no!

A sternly worded letter!

That ought to put a stop to medical cost inflation.

Getting on the same page

One issue I've been interested in concerning physicians and patients is whether their priorities are aligned. For example, the doctor might be most concerned about a patient's blood pressure or blood sugar, whereas the patient is more worried about skin tags or spider veins, or joint pain. If the patient finds the doctor isn't taking her concerns seriously, she may lose trust and be less inclined to follow the doctor's advice about taking medications for the conditions the doctor feels are important. On the other hand, those problems might in fact be very important to the patient and have a big effect on his quality of life. Just because the doctor doesn't see them as life-threatening, or perhaps as not affecting his pay-for-performance contract, doesn't mean he doesn't have an obligation to the patient to take them seriously.

Donna Zulman et al, in the new Journal of General Internal Medicine, looked at this question for people with diabetes and co-morbid conditions. They found that while many people's priorities lined up fairly well with their doctors', the rate of agreement went down for people in poorer health status, and people who said they had other competing problems that were more pressing than their health. This is not surprising to me -- doctors just aren't very good at diagnosing people's life worlds, as we say, and when those are harder to navigate, it's likely that the doctor will miss what's really going on with the person.

It also turns out that there are some differences generally in doctor and patient priorities. Doctors tend to rank hypertension higher than patients; and, no big surprise, patients are likely to rank symptomatic conditions higher than their doctors do. Hypertension has no symptoms, although it is very dangerous, but people have to struggle every day with pain, breathing difficulties, and cosmetic problems. So this comes out pretty the way I thought it would.

The solution? Doctors need to do a better job of listening, and most important of giving up control of the agenda. They are never going to have much success accomplishing their own goals if they can't serve the patient's goals, let alone if they don't even bother to understand what those are or dismiss them. Unfortunately, this sort of misalignment is very common, because it is embedded in the culture of medicine.

Right now we're thinking about ways of observing and measuring how it is reflected in the interaction process during a visit. I'll keep you posted.

Some perspective

For those who believe the Undiebomber is an existential threat to western civilization that requires repealing the Bill of Rights and electing Sarah Palin president, you may be interested to know that in the United States alone there were more than 11 million commercial airline departures in 2007 (the most recent year for which data are available), resulting in 12 1/2 billion passenger miles.

If it continues to be the case that once every ten years or so some lost wackjob succeeds in getting onto an airplane with an explosive device concealed in some article of clothing or body cavity and, for once, actually succeeds in blowing up the plane, even if you are a frequent flyer your chances of being killed or injured in the incident are less than your chances of being eaten by a shark. So stay out of the water.

And speaking of rubes . . .

Richard Branson? He's generally considered to be no fool.

A few more words on health care costs

As I noted last week, there are a couple of essays in the latest NEJM that touch on this cost issue. Weinstein and Skinner make the point, rather over-elaborately I would say, that within a given regime of cost-effectiveness, spending more will tend to produce better outcomes; but that you can get the same or better outcomes for less money by shifting to more cost-effective service delivery. The point seems to be that it would be relatively painless -- at least for consumers -- to begin by worry about comparative effectiveness and not worrying so much about setting budgets or trying to make the socially radioactive decision about how much we're willing to spend per QALY. If we can just stop doing useless or more expensive but no better stuff, we can get ahead without confronting the Death Panels.

A group to large to enumerate (starting with Stephen Swensen and ending with Donald M. Berwick), in the same issue, discusses the need to transform the medical industry from a "cottage" industry in which each practice is akin to an independent artisanal shop to a modern, post-industrial model in which there are overarching systems in place to assure quality and conformity to standards. You don't want every airplane you fly in to be independently owned and operated by its pilot, with essentially no regulation except the right to sue him after you crash; so why do people want their doctors to work that way?

This seems fair enough in principle -- much of the resistance to performance standards in medicine stems more from romantic nostalgia than from good sense. Still, it's very tricky because every patient is indeed different and there are a fairly limited number of standards that are always, or almost always, right for everybody. Hitting the sweet spot between standards of practice and clinical judgment is really, really hard.

In any event, I want to leave this discussion for now with the observation that libertarians have painted themselves into a very awkward, weird corner on this issue. They are insisting on their absolute right to receive unlimited amounts of useless or even harmful drugs and medical procedures, and to make other people pay for it, so long as they are lucky enough to be over 65, privately insured, or indigent and categorically eligible. Note that even people who aren't so lucky as to have insurance still have to help pay for the lucky people's unlimited, useless medical care because part of it is funded from general tax revenues. That's the libertarian, right wing, Republican, Sarah Palin position. Literally. Unequivocally. And note that no proposal for rationing or cost effectiveness analysis stops somebody who can afford it from paying out of pocket for a brain transplant or whatever else they want -- these proposals only prevent people from forcing others to pay. And yet libertarians decry them.

That is truly weird, warped and twisted. Do they ever actually think?

Sorry for limited posting . . .

I've been caught up in a bit of a creative frenzy here. So, to distract y'all while that's going on, this is probably a total boondoggle but if it ever actually works out we'll enter an entirely new age of civilization. Your tax dollars are still at work trying to develop controlled nuclear fusion power, as they have been for more than 40 years. (When I was in college, Lyndon LaRouche claimed they had already done it but the oil companies were suppressing it.)

As you probably haven't heard from CBS News, there are a whole lot of credible people such as the CEOs of several large oil companies who are saying that Peak Oil is now, 2010. I've pretty much steered clear of the Peak Oil cultists here because what the heck do I know about the subject of petroleum? But if they are right the world is going to change much faster than you think. Just a thought for a chilly February day.

Happy medical costs day!

Today the Centers for Medicare and Medicaid Services (oddly abbreviated CMS) released it's annual report on national medical expenditures. (Actually they released it yesterday but it was embargoed and I'm going legit here so I waited.) Some highlights:

• In 2009, [National Health Expenditures] NHE is projected to have reached $2.5 trillion and grown 5.7%, up from 4.4% in 2008 (the latest available historical year), while GDP, with the economy still in recession, is anticipated to have declined 1.1%.


• As a result of NHE growth outpacing GDP growth in 2009, the health share of GDP is expected to have increased from 16.2% of GDP in 2008 to 17.3% in 2009, which would represent the largest one-year increase in history.


• In 2010, NHE growth is expected to decelerate to 3.9% while GDP is anticipated to rebound to 4.0% growth. [Hah! -- C] Much of the projected slowdown in NHE growth is attributable to a deceleration in Medicare spending growth (1.5% in 2010, from 8.1% in 2009) that is driven by a 21.3% reduction in Medicare physician payment rates called for under current law’s Sustainable Growth Rate (SGR) provisions. [Which ain't gonna happen -- Congress will revise this. -- C]


• Private spending in 2010 is projected to grow just 2.8%, which is related to both declining private health insurance enrollment because of sustained high rates of unemployment and the expiration of Federal subsidies associated with COBRA coverage.


• Over the projection period (2009-2019), average annual health spending growth (6.1%) is anticipated to outpace average annual growth in the overall economy (4.4%). By 2019, national health spending is expected to reach $4.5 trillion and comprise 19.3% of GDP.

And yes, a higher percentage of that 19.3% of GDP will be public expenditures, as private health insurance becomes affordable and available to fewer and fewer people. Specifically, "As a result of more rapid growth in public spending, the public share of total health care spending is expected to rise from 47% in 2008, exceed 50% by 2012, and then reach 52% by 2019."

This is obviously completely unsustainable. It isn't going to happen, but it can not happen in a bad way, or it can not happen in a good way. The bad way is the way it's happening now -- more and more people being squeezed out entirely, and others being tossed onto state Medicaid plans that provide inferior care with major gaps in coverage, and which will just get worse and worse and more and more restrictive.

The good way is that we spend less money, but more wisely, cover everybody, and get better results, just like people in sensible countries. There are a few essays in today's NEJM which discuss how we can do this. I'll get to them, with my own two cents, anon.

Information exchange between doctors and patients

Sorry for the straightforward title, I'm not feeling particularly creative or snarky today.

I think it would surprise you how little we really know about what kinds of information doctors give to patients, how they go about it, and how it is understood. Studies of communication between physicians and patients have tended to focus more on interaction process -- the affective, interpersonal and social role dimensions -- than on instrumental communication -- the literal content of information as given and received. Much of the work uses coding systems -- notably the Roter Interactional Analysis System -- that provide only very limited characterization of the subject matter of speech. On of my main projects is to improve on that using coding that separates interaction process from subject matter and allows the subject matter to be coded as specifically as you might want for a given research question.

We do know that in routine prescribing, doctors typically provide very little information. I'm sure it's been your own experience that they pretty much just say, "Take these pills, X times a day." They might mention a possible side effect. I have found that my doctor hasn't bothered to mention issues of major importance that show up on the label, and he certainly doesn't explain how the drugs work. Doctors don't like to mention possible side effects because they are afraid that it will either discourage people from taking the meds, or predispose them to think they are experiencing the side effects when they are not.

I have diagnosed hypertension and hypercholesterolemia, both well controlled by pills. I happen to know a lot about the risks associated with these conditions and something about the mechanisms of action and the side effects associated with the drugs I take, but it's not because my doctor ever explained it to me. He may have just assumed I knew given my profession; I suspect that doctors are afraid of telling people information they might already know because it might seem patronizing. But they don't have the skill to assess people's need for information.

In the case of diagnoses perceived as more serious, doctors do tend to provide more information. However, people are often quite distressed when they first are told they have cancer or HIV or kidney disease, and they just don't absorb what they are told. This is a problem which is well-recognized, but that doesn't mean it is properly dealt with.

More fundamentally -- and this is the issue my latest proposal addresses -- it seems pretty clear that a large proportion of the population just doesn't have the pre-existing conceptual framework on which to hang new biomedical information. We do a terrible job of teaching biology in elementary and high school, and nowadays even college graduates tend to pursue narrow, career-focused courses of study that may omit biology. And by the way, if you want to understand biology you have to understand evolution, which in its modern form that includes the mechanisms of inheritance and the functioning of DNA and the proteome, is the basic organizing principle of all biology. You can't understand cancer, or infectious disease, the immune system, or much of anything else if you don't understand that.

But the fact is, lots of people don't understand what a cell is, how a virus replicates, or how the body regulates essential conditions from blood sugar to blood pressure. So, the doctor may say a lot of words but they don't congeal into a coherent understanding. People may also mishear specific words -- e.g. in one example I encountered "toxic gases" for "toxoplasmosis." Therefore, doctors sometimes resort to vague and possibly misleading metaphors, overly simplistic explanations, or even patently false explanations, just to satisfy people. Sometimes this gets them to do what the doctor wants, so what the heck, right? Sometimes it doesn't.

So the challenge is to learn how to break down essential biomedical information into explanatory models that are accurate, but can be interpreted given people's existing frameworks. You first need to figure out where each individual's starting point is, and then build on it. In general, doctors don't know how to do this.

Whaddya Know?

If you're like most people, not much, as it turns out, when it comes to your own diagnoses and the pills you take. If that sounds a little harsh, I'm sorry, but if there's one thing I do know after years of studying people's experience as patients it's that you have to assume they don't know what medications they are taking, why they take them, what pills do what; and the way they understand whatever diseases the doctors have told them they have is not very much like the way the doctors understand them.

Nowadays, more and more people are taking more and more pills. People with kidney disease, diabetes, and other unfortunately pretty common ailments often have 8 or 12 or even more prescriptions. I'll let you in on a little secret: hardly anybody with that many prescriptions actually takes them all consistently. (Actually, at least half the people with only a few prescriptions don't take them either.) People make their own decisions about which ones are important, or they decide that one or another is responsible for a symptom they conclude is a side effect. So they stop taking some of the meds, or take them some of the time. One guy I know of even has rotation system. But if you ask them which pills do what, they probably can't tell you, or their answer won't correspond to what the doctor thinks.

Similarly, if you ask somebody who has been diagnosed with diabetes, or HIV, or even hypertension to explain what the disease is -- what causes it, how the disease process works, how the treatment works, what the long-term toll is on the body -- it's unlikely that they will give you a coherent story, and if they do, it probably won't resemble what's in the medical textbooks.

Sometimes there are very consistent patterns to this disconnect. For example, HIV medications lose effectiveness over time, particularly if people don't take them consistently, because the virus evolves resistance. The process is similar in general to the development of bacterial resistance to antibiotics, although viruses and bacteria reproduce in a totally different way. However, the vast majority of people with HIV interpret drug resistance as a change in their bodies, not the virus. Often they simultaneously hold a contradictory idea, that the virus is intelligent and it can "figure out" how to get around the drugs, but the idea that their body becomes "immune" to the drugs is usually the first resort.

So, I'm curious as to how people's ideas about their various diseases are related to their self-care behavior and their general coping. Maybe it doesn't really matter what story you tell yourself, as long as it works for you. Or maybe having understanding that is more like your doctor's understanding helps you work together with your doctor more effectively to stay healthier. It actually isn't obvious and it probably depends on the specifics of the discordance or concordance of the beliefs, and the kinds of decision rules that people use, and how they interact with each other. But, outcomes aside, there is an ethical question. Shouldn't people be able to make well-informed choices? What constitutes adequate information, and what is the physician's responsibility to assure that people have it?

So, these are all questions that I'm working on.

News you can use?

I get a lot of e-mail from various organizations, authors and businesses touting health advice and resources for the average schmo to learn how to glow with the incandescence of well being and all that. Since I really don't intend this to be Ask Dr. Wiseguy (I'm not a real doctor anyway, I'm a doctor of philosophy), I usually just delete it, but what the heck, as long as we're here:

The Clinton Foundation has joined with the Heart Association to help parents and children combat the epidemic of childhood obesity and inactivity. I don't know how much good it will do for me to link to their web site but if you have kids, know any kids, or know anybody who has kids it probably can't hurt to take a look and get some ideas. They're calling the whole thing the Alliance for a Healthier Generation.

WebMD has been begging me for a link forever, it seems like. I keep fighting them off with my policy of not linking to commercial sites, but after thoroughly checking them out I think they're okay. They are supported by advertising but they really do have a firewall between advertising and editing, with additional beneficial restrictions on the content and presentation of ads. Their information generally seems fair and balanced, and basically they're just using the classic business model of advertiser-supported magazine publishing on the web instead of on paper, so what the heck? They've been particularly pushing the heart section on me.

Do, however, ignore the advertising. You will see disease mongering for fibromyalgia, which is something people really do experience but is not curable by drugs; and ads for antidepressants which are pretty much a fraud. If you can trust yourself to put black tape over the ads, you might find it useful.

Okay, let's get this over with

Since the whole subject of how NIH funding gets allocated appears to be of considerably less interest to the public than I had imagined, I'll just wrap up this series and move on. After a long review and rethinking process, NIH made some changes to its extramural funding policies. The single most substantive change is probably that you only get one chance to resubmit an unsuccessful application rather than two. This is a bit anxiety-provoking to us applicants, because they also say that it is almost impossible to get funded on the first round. You need to get those reviewers' comments, respond to them and modify your proposal accordingly, in order to have a realistic chance. But now you only get to do it once.

Another anxiety-provoking change is that they have drastically reduced the page limits for proposals - from 25 to 12 for a large R01, and from 15 to 6 for a developmental proposal such as the one I just submitted. Actually there is also a so-called Specific Aims page so you really have 13 and 7 pages, respectively, but the Specific Aims is kind of a "tell 'em what you're gonna say" section so it doesn't really represent additional information. You also get to put across something of your suitability to do the work through your biosketch -- which now includes a tailored "personal statement" for each proposal.

For you, the people who are paying for all this, the most important change, in my view, is kind of subtle and its hidden in the application instructions and the review criteria. There has always been a tension in NIH peer review between the imperative that proposed studies have a high expectation of success; and the criterion of innovation.

If you think you have a bright idea that nobody else has had yet, and it might really transform the way we think about some problem or lead to a breakthrough in treatment, you might think you have a good shot at getting funding from NIH but historically, that hasn't really been true. Most of the work that gets funded is incremental, stays within accepted paradigms, and is even repetitious. People with new ideas have really struggled to get support because the process has been inherently conservative. They haven't wanted to invest in projects and ideas that might not work out. If you look at the side-by-side comparison of the old and new applications, you will see, even though it isn't really advertised, that the new language puts a lot more emphasis on innovation. Actually, it explicitly calls for profound innovation:

• Explain how the proposed project will improve scientific knowledge, technical capability, and/or clinical practice in one or more broad fields.
• Describe how the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field will be changed if the proposed aims are achieved.
• Explain how the application challenges and seeks to shift current research or clinical practice paradigms.
• Describe any novel theoretical concepts, approaches or methodologies, instrumentation or intervention(s) to be developed or used, and any advantage over existing methodologies, instrumentation or intervention(s).

My problem is, I have only 6 pages to convince people who have been working in the field all their lives, and think they know everything there is to know about it, that I, a new, junior investigator who they have never heard of, have thought up something that will shift their current research paradigms and change the concepts, methods and technologies that drive their field. And in those same 6 pages I have to explain everything I'm going to do to prove it.

What do you think my chances are? We'll see.